Novel heteroaryl-urea compounds as KV7.2 inhibitors

Abstract

The present invention relates to a compound represented by general formula (I'): TIFF2024542881000958.tif29161 (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Y 1 , Y 2 , Y 3 and n is as defined herein), or a solvate or pharma- ceutically acceptable salt thereof, compositions comprising said compounds, processes for making said compounds, and methods of using said compounds.

Description

[Technical field]

[0001] The present invention relates to novel compounds, particularly pyridine compounds, useful as Kv7.2 enhancers (or positive modulators), their manufacture, pharmaceutical compositions containing the compounds, kits, and their use as medicaments for the therapeutic and / or prophylactic treatment of Kv7.2-related 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 includes five proteins encoded by genes KCNQ1, KCNQ2, KCNQ3, KCNQ4, and KCNQ5 in humans. KCNQ proteins form homo- 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 channels as well as 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 link to epileptic encephalopathy (EE) (Zhao et al., 2020). Whether primary or secondary EE, seizure activity worsens clinical outcomes and alters normal neurodevelopment (von Deimling, Helbig and Marsh, 2017). Pediatric epilepsy affects approximately 1 in 200 children (Simkin and Kiskinis, 2018) causing cognitive, behavioral and neurological disorders (Waaler et al., 2000). In the case of certain pathogenic KCNQ2 mutations, developmental delay is 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 to transform neurodevelopmental trajectories by treating neural network instability involved in EE (Kessi et al., 2020).

[0004] The association between epilepsy and autism is robust (Srivastava and Sahin, 2017) and stems from a convergent phenotype caused 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 among the top 30 of all known de novo mutations in ASD (Zhao et al., 2020).

[0005] Another defining feature of ASD, atypical sensory processing (ASP) (Thye et al., 2018), is also driven by convergent genetics seen in twin-control studies (Neufeld et al., 2021). The biology involved in increased sensory sensitivity has been studied in preclinical models, where multisensory neuronal hyperexcitability emerges regardless of the genetic manipulation that initially drives pathological neurogenesis. 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 to modify neurodevelopmental trajectories in ASD by normalizing network stability, neural information processing, and sensory abnormalities, ultimately contributing to atypical social and repetitive behaviors in ASD. It is also interesting to note that KCNQ2 knockout mice exhibit repetitive behaviors as well as abnormal exploratory and social behaviors ( Kim et al., 2019 ).

[0006] Kv7.2 enhancers also showed promise in syndromic neurodevelopmental disorders due to the prevalence and impact of epilepsy ( Budisteanu et al., 2020 ), for example, epilepsy is common in Angelman syndrome (>80%), with most beginning before age 3 years ( Fiumara et al., 2010 ).

[0007] Another neurodevelopmental disorder, Dup15q syndrome (Dup15q), is caused by a partial duplication of chromosome 15 that confers a considerable risk of autism spectrum disorder, epilepsy, and intellectual disability. Induced pluripotent cells derived from Dup15q patients show 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 show potential to transform this neurodevelopmental disorder.

[0008] 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). Thus, Kv7.2 enhancers may positively impact fragile X by acting on both epilepsy and sensory processing.

[0009] Infantile epilepsy is associated with intellectual disability, and KCNQ2 de novo mutations are significantly associated with intellectual disability (Zhao et al., 2020). Kv7.2 enhancement may address the underlying biology that exacerbates disability.

[0010] 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.

[0011] Among behavioral disorders, Kv7.2 enhancers have shown promise in attention-deficit hyperactivity disorder (ADHD) as well as 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 effects in patients by acting on the brain's reward center (Tan et al., 2018). The significant reduction in depressive symptoms observed with retigabine places Kv7.2 enhancers as a therapeutic candidate for MDD.

[0012] The therapeutic potential of Kv7.2 enhancers in pain sensitivity is supported by the localization of Kv7.2 channels in dorsal root ganglia and their established role in pain perception (Brown and Passmore, 2009). Nonselective Kv7.2 enhancers have shown efficacy in reducing 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 shows efficacy in controlling spreading depression, a wave of cellular depolarization associated with migraine headaches (Aiba and Noebels, 2021).

[0013] Within the scope of sensory abnormalities, abnormal plasticity of KCNQ2 channels is strongly linked to the induction of tinnitus (Li, Choi and 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 the closure of Kv7.2 channels (Liu, Glowatzki and Fuchs, 2015). Retigabine prevents the development of tinnitus in preclinical models (Li, Choi and Tzounopoulos, 2013). As evidence supporting how KCNQ2 pathology is linked across indications, it is intriguing to find that tinnitus and hyperacusis are more prevalent in ASD than in the general population (Danesh et al., 2015).

[0014] In neurodegenerative diseases, dysregulated K+ homeostasis 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 excitability was found early in a presymptomatic in vivo system (Kuo et al., 2004) that is responsible for disease progression. Recently, clinical trials in ALS with retigabine have shown efficacy against functional biomarkers of ALS ( Wainger et al., 2021 ) and preclinically protect against peripheral neuropathy ( Nodera et al., 2011 ).

[0015] In Alzheimer's disease (AD), neuronal hyperexcitability and network instability (Frere and Slutsky, 2018) are early features of both IPSC (Ghatak et al., 2019) and genetic in vivo models of sporadic AD (Palop et al., 2007; Kazim et al., 2017; Styr and Slutsky, 2018). Network instability exacerbates proteinopathy (Dolev et al., 2013; Frere and Slutsky, 2018) and has consequences for patients (Vossel et al., 2013; Lam et al., 2017).

[0016] Because motor neuron and cortical neuron degeneration 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.

[0017] Therefore, enhancing the activity of Kv7.2 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.

[0018] WO 2020 / 163268 relates to pyridine urea derivatives as KCNQ potentiators.

[0019] US Patent No. 5,384,330 relates to pharmacologically active 1,2,4 triaminobenzene derivatives that modulate potassium ion channels Kv7.2-Kv7.5 (KCNQ2-KCNQ5) for the treatment of drug-resistant epilepsy. The compounds showed tolerability problems and other side effects.

[0020] Furthermore, bioactivation of drugs to produce chemically reactive metabolites is an undesirable property for drugs intended for use in patients due to the observation that most drugs that cause severe idiosyncratic clinical adverse reactions form reactive metabolites that can be covalently bound to proteins (Park et al., 2011). Some reactive metabolites can form adducts with glutathione (GSH) when used as a scavenger in in vitro experiments. Thus, the formation of GSH adducts in human liver microsomes can provide valuable information on the likelihood of molecules undergoing bioactivation to reactive metabolites (Dieckhaus et al., 2005; Brink et al., 2014), and since GSH adduct formation leads with a high probability to increased levels of covalent binding to liver microsomal proteins, GSH adduct formation can further serve as a surrogate marker of covalent binding to human liver proteins (Evans et al., 2004). Therefore, compounds that do not form GSH adducts when incubated in human liver microsomes under conditions of metabolic activation in vitro may be considered to have a low risk of reactive metabolite formation in humans ( Brink et al., 2017 ).

[0021] To date, no drug that acts 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 a modulator of Kv7.2 that provides therapeutic benefits.In addition, it would be beneficial to have a modulator of Kv7.2 that is more highly selective than other Kv7 channels.There is a need for a Kv7.2 modulator that provides a combination of favorable pharmacological properties, such as, for example, potency, selectivity, and metabolic stability.

[0022] It is therefore an object of the present invention to provide selective Kv7.2 enhancers having 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, preferably exhibiting a beneficial tendency to reduce the formation of GSH adducts when incubated in human liver microsomes under conditions of metabolic activation.

[0023] References: Aiba, I. and Noebels, JL (2021) “Kcnq2 / Kv7.2 controls the threshold and bihemispheric symmetry of cortical spreading depolarization,” Brain: a journal of neurology.doi:10.1093 / brain / awab141. Berry-Kravis, E. (2002) “Epilepsy in fragile X syndrome,” Developmental medicine and child neurology. Wiley Online Library, 44(11), pp.724-728. Brown, DA and Passmore, GM (2009) “Neural KCNQ(Kv7) channels,” British journal of pharmacology, 156(8), pp. 1185-1195. Brink,A.,et al.(2014);Rapid Commun.Mass Spectrom.,28,2695-2703. Brink,A.,et al.(2017);Drug Discovery Today,22,751-756. Budisteanu,M.et al.(2020)”Treatment of Epilepsy Associated with Common Chromosomal Developmental Diseases,” Open life sciences.Walter de Gruyter GmbH,15(1),pp.21-29. Danesh,A.A.et al.(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. von Deimling,M.,Helbig,I.and Marsh,E.D.(2017)”Epileptic Encephalopathies-Clinical Syndromes and Pathophysiological Concepts,” Current neurology and neuroscience reports,17(2),p.10. Dieckhaus,C.M.,et al.(2005);Chem.Res.Toxicol.,18,630-8. 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. Evans,D.C.et al.(2004);Chem.Res.Toxicol.,17,3-16. Fink,J.J.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. Fiumara,A.et al.(2010)”Epilepsy in patients with Angelman syndrome,” Italian Journal of Pediatrics,p.31.doi:10.1186 / 1824-7288-36-31. Frere,S.and Slutsky,I.(2018)”Alzheimer’s Disease:From Firing Instability to Homeostasis Network Collapse,” Neuron,97(1),pp.32-58. 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. Gunthorpe,M.J.,Large,C.H.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. Hardiman,O.et al.(2017)”Amyotrophic lateral sclerosis,” Nature reviews.Disease primers,3,p.17071. Holder,J.L.,Jr and Quach,M.M.(2016)”The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations,” Epilepsia,57(10),pp.1651-1659. 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. 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(Pt 4),pp.953-962. 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. Kato,M.et al.(2013)”Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation,” Epilepsia,54(7),pp.1282-1287. Kazim,S.F.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. Kessi,M.et al.(2020)”Intellectual Disability and Potassium Channelopathies:A Systematic Review,” Frontiers in genetics,11,p.614. Kim,E.C.et al.(2019)”Heterozygous loss of epilepsy gene KCNQ2 alters social,repetitive,and exploratory behaviors,” Genes,Brain and Behavior.doi:10.1111 / gbb.12599. Korsgaard,M.P.G.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. Kuo,J.J.et al.(2004)”Hyperexcitability of cultured spinal motoneurons from presymptomatic ALS mice,” Journal of neurophysiology.physiology.org,91(1),pp.571-575. Lam,A.D.et al.(2017)”Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer’s disease,” Nature medicine,23(6),pp.678-680. Lang,P.M.et al.(2008)”Retigabine reduces the excitability of unmyelinated peripheral human axons,” Neuropharmacology,54(8),pp.1271-1278. 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. 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. 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. McCullagh,E.A.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. 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. Ng,F.L et al.(2011).Expression and function of the K+channel KCNQ genes in human arteries.British Journal of Pharmacology,162(1),42-53. Nodera,H.et al.(2011)”Neuroprotective effects of Kv7 channel agonist,retigabine,for cisplatin-induced peripheral neuropathy,” Neuroscience letters,505(3),pp.223-227. Palop,J.J.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. Park,B.K.,et al.(2011);Nat.Rev.Drug Discov,10,292-306. Pasinelli,P.and Brown,R.H.(2006)”Molecular biology of amyotrophic lateral sclerosis:insights from genetics,” Nature reviews.Neuroscience,7(9),pp.710-723. 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. Simkin,D.and Kiskinis,E.(2018)”Modeling Pediatric Epilepsy Through iPSC-Based Technologies,” Epilepsy currents / American Epilepsy Society,18(4),pp.240-245. 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. Srivastava,S.and Sahin,M.(2017)”Autism spectrum disorder and epileptic encephalopathy:common causes,many questions,” Journal of neurodevelopmental disorders,9,p.23. 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. 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. Tanaka,M.et al.(2012)”GABRB3,Epilepsy,and Neurodevelopment,” in Noebels,J.L.et al.(eds.)Jasper’s Basic Mechanisms of the Epilepsies.Bethesda(MD):National Center for Biotechnology Information(US). Thye,M.D.et al.(2018)”The impact of atypical sensory processing on social impairments in autism spectrum disorder,” Developmental cognitive neuroscience.Elsevier,29,pp.151-167. Vossel,K.A.et al.(2013)”Seizures and epileptiform activity in the early stages of Alzheimer disease,” JAMA neurology,70(9),pp.1158-1166. Waaler,P.E.et al.(2000)”Prevalence,classification,and severity of epilepsy in children in western Norway,” Epilepsia,41(7),pp.802-810. Wainger,B.J.et al.(2014)”Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons,” Cell reports,7(1),pp.1-11. Wainger,B.J.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. Wang,H.S.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. 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. 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. 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. 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

[0024] In some embodiments, the compound of formula (I'): [ka] (In the formula, R 1 , R 2 , R3 , R 4 , R 5 , Y 1 , Y 2 , Y 3 , n and R 6 Provided herein is a pharmaceutical composition comprising a compound of the formula:

[0025] In a further aspect, the present invention provides a compound of formula (I') or a solvate or pharma- ceutically acceptable salt thereof.

[0026] In a further aspect, the present invention provides a process for the preparation of a compound of formula (I'), or a solvate or pharma- ceutically acceptable salt thereof.

[0027] In a further aspect, the present invention provides a compound of formula (I'), or a solvate or pharma- ceutically acceptable salt, when prepared according to the processes described herein.

[0028] In a further aspect, the present invention provides a compound of formula (I'), or a solvate or pharma- ceutically acceptable salt thereof, or a pharmaceutical composition comprising same, for use as a therapeutically active substance.

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

[0032] 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 pharma- ceutically acceptable salt thereof, or a pharmaceutical composition comprising same.

[0033] 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 pharma- ceutically acceptable salt thereof, or a pharmaceutical composition or pharmaceutical composition for use comprising same, b) providing a kit containing the product, the product being tested, and instructions for use.

[0034] In a further aspect, the present invention provides the invention as described above.

[0035] The compounds of formula (I') described herein, or solvates or pharma- ceutically acceptable salts thereof, provide a combination of favorable pharmacological properties, such as potency, selectivity, and metabolic stability. Adequate metabolic stability is important to ensure adequate pharmacological half-life, best achieved with compounds that have human hepatic microsomal clearance of less than 20 uL / min / mg. Selectivity within the Kv7 family is desirable to avoid action on tissues that have no therapeutic potential for the indications described in the present invention. For example, action on Kv7.4 and Kv7.5 in skeletal and smooth muscle affects the function of human arteries, and KCNQ2 expression is minimal or undetectable in these tissues (Ng et al., 2011).

[0036] The same embodiments as above are included for compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof. [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , n and R 6 is as defined herein) DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] definition It should be understood that features, integers, characteristics, compounds, chemical moieties or groups described in connection with a particular aspect, embodiment or example of the invention are applicable to any other aspect, embodiment or example described herein, except where inconsistent therewith. All of the features disclosed herein (including any accompanying claims, abstract and drawings), and / or all of the 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, any embodiment, or any steps of any method or process so disclosed disclosed herein (including any accompanying claims, and abstract).

[0038] 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, etc.

[0039] As used herein, the terms "including," "containing," and "comprising" are used in their open-ended sense.

[0040] As used in this disclosure, the articles "a" and "an" can 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" can mean one element or more than one element.

[0041] As described herein, the compounds of the present disclosure may be "unsubstituted" or "substituted" with one or more substituents (e.g., 1, 2, 3, 4, or 5), such as those generally shown herein or exemplified by the particular classes, subclasses, and species of the present disclosure. In general, the term "substituted" refers to the replacement of a hydrogen atom in a given structure with a particular substituent. In some embodiments, two or more hydrogen atoms are replaced with a particular substituent (e.g., two hydrogen atoms are replaced with an oxo substituent). The combination of substituents contemplated by the present disclosure is typically obtained by forming a stable or chemically suitable compound. 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.

[0042] As used herein, the term "unsubstituted" can mean that the specified group has no substitutions beyond the recited moieties (e.g., where the valence is satisfied by hydrogen).

[0043] The term "effective amount" or "therapeutically effective amount" refers to an amount of a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, or a pharmaceutical composition as described above, sufficient to produce a desired therapeutic result, such as reducing the severity of the duration, stabilizing the severity, or eliminating one or more signs, symptoms, or causes of a disease, disorder, or disability. For therapeutic use, the beneficial or desired result may include, for example, reducing one or more symptoms attributable to the disease, disorder, or disability (biochemical, histological, and / or behavioral), including its complications and intermediate pathological phenotypes presented during the development of the disease, disorder, or disability, enhancing the quality of life of a person suffering from the disease, disorder, or disability, reducing the dose of another drug required to treat the disease, disorder, or disability, enhancing the effect of another drug, delaying the progression of the disease, disorder, or disability, and / or prolonging the survival of the patient.

[0044] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the free base or free acid, without being 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. Furthermore, 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. 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.

[0045] As used herein, the term "excipient" or "pharmaceutical excipient" refers to any pharma- ceutical acceptable additive that may be used in the manufacture of a drug or pharmaceutical composition, such as a tablet containing a compound described herein or a tautomer or pharma- ceutical acceptable salt) as an active ingredient. Various substances may be encompassed by the term excipient, including, but not limited to, any substance used as a diluent, filler, extender, binder, disintegrant, glidant, wetting agent, coating, emulsifier or dispersant, compression / encapsulation aid, cream or lotion, lubricant, solution for parenteral administration, material for chewable tablets, sweetener or flavoring agent, suspending / gelling agent, or wet granulation agent. Disintegrants refer to additives that swell and dissolve when wet, causing the tablet to break down in the body and release the active ingredient for absorption. Examples include crospovidone, crosslinked polymers such as croscarmellose sodium, and modified starches such as sodium starch glycolate. Fillers refer to additives that fill the size of the tablet by increasing the bulk volume. Fillers allow the final product to have an appropriate volume for patient handling. Examples of fillers are vegetable cellulose, lactose, starch, mannitol, etc. Specific examples include lactose monohydrate such as Pharmatose 200M, microcrystalline cellulose (MCC) such as Avicel PH101 or Avicel PH102, and spray-dried lactose such as Fast Flo 316™. Binders refer to additives that hold the ingredients together in a tablet. Binders ensure that tablets and granules can be formed with the required mechanical strength. Examples of binders are polyvinylpyrrolidone (PV), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), cellulose, sugar alcohols such as sorbitol, proteins such as gelatin, and polymers such as PVP, e.g., copovidone (PVP / VA64), PEG, etc. Lubricants refer to additives that prevent ingredients from clumping together and from sticking to the tablet punch or capsule filling machine. The lubricant also ensures that tablet formation and release can occur at a low rate between the active ingredient and the wall.Examples of lubricants are minerals such as talc or silica, and fats such as stearin, magnesium stearate, etc. Coatings can include, for example, cellulose acetate phthalate, ethylcellulose, gellan gum, maltodextrin, enteric coatings, etc., and compression / encapsulation aids include, for example, calcium carbonate, dextrose, fructose dc (dc--"directly compressible"), honey dc, lactose (anhydrous or monohydrate; optionally in combination with aspartame, cellulose or microcrystalline cellulose), starch dc, sucrose, etc. Creams or lotions include, for example, maltodextrin, carrageenan, etc. Chewable tablet materials include, for example, dextrose, fructose dc, lactose (monohydrate, optionally in combination with aspartame or cellulose), etc. Suspending / gelling agents include, for example, carrageenan, sodium starch glycolate, xanthan gum, etc. Sweeteners include, for example, aspartame, dextrose, fructose dc, sorbitol, sucrose dc, etc. Wet granulation agents include, for example, calcium carbonate, maltodextrin, microcrystalline cellulose, etc. In some cases, the term "additive" includes a pharma- ceutically acceptable carrier. Those skilled in the art know the appropriate pharmaceutical compositions used to treat patients and methods for their preparation.

[0046] The term "patient" or "subject" can include both mammals and non-mammals. Examples of mammals include, but are not limited to, any member of the class Mammalia: humans; non-human primates, such as 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.

[0047] As used herein, the term "treat" or "treatment" refers to delaying 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 develop or is expected to develop. Thus, these terms can include improving one or more existing symptoms of a disease, disorder, or disability; preventing one or more additional symptoms; improving or preventing the underlying cause of one or more symptoms; inhibiting a disease, disorder, or disability, for example, preventing the onset of a disease, disorder, or disability; relieving a disease, disorder, or disability; causing the regression of a disease, disorder, or disability; relieving symptoms caused by a disease, disorder, or disability; or arresting or alleviating a symptom of a disease, disorder, or disability.

[0048] The compounds of the present invention and 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 generally called hydrates. Hydrates may include compositions that contain stoichiometric amounts of water and compositions that contain variable amounts of water.

[0049] As used herein, the term "prophylaxis" includes preventing or delaying the appearance of clinical symptoms of a disease, disorder, or disability that develops in a patient or subject, particularly a human, who may be afflicted with or susceptible to a disease, disorder, or disability described herein, but who has not yet experienced or shown clinical or subclinical symptoms of the disease, disorder, or disability.

[0050] 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 being appropriate for practicing the disclosed methods or using the disclosed compositions.

[0051] 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 within 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.

[0052] As used herein, a numerical range can include consecutive integers. For example, a range expressed as "0 to 5" includes 0, 1, 2, 3, 4, and 5.

[0053] A "metabolite" is a product produced by metabolism in the body of a particular 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, for example, from the oxidation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, and the like, of the administered compound. Thus, the present invention includes metabolites of the compounds of the present invention, including compounds produced by a process comprising contacting a compound of the present invention with a mammal for a period of time sufficient to yield a metabolic product thereof.

[0054] The term "package insert" is used to refer to instructions typically included in commercial packaging for a therapeutic agent that contain information about the indications, usage, dosage, administration, contraindications, and / or warnings regarding the use of such therapeutic agent.

[0055] The terms "compounds of the invention" and "compounds of the invention" and "compound or formalin (I')" or "compound of formula (I)" include compounds of formula (I') or formula (I), compounds selected from any of formulas (I*), (I**), (II), (III), etc., compounds selected from Tables 1-9, solvates, pharma- ceutically acceptable salts, stereoisomers, geometric isomers, tautomers, metabolites, prodrugs, polymorphs, and mixtures thereof.

[0056] The symbol "*" at the end of a bond or the symbol "---" drawn through a bond each indicates 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] It is meant that the substituent is attached to the remainder of the molecule as indicated.

[0057] 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.

[0058] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance may occur, but does not necessarily have to occur, and that the description includes cases where the event or circumstance occurs and cases 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. "Optionally substituted" means that a given substituent may be unsubstituted or may be further substituted with a particular substituent as defined herein and listed in different embodiments. For example, as a non-limiting example, R 6 The expression is one or two C 1~6 cyclobutyl optionally substituted with alkyl; R 6 is unsubstituted cyclobutyl or 1 or 2 C 1~6 It is meant to include cyclobutyl substituted with alkyl.

[0059] 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, R" appears twice, and in a compound defined as "independently carbon or nitrogen," both R"s may be carbon, both R"s may be nitrogen, or one R" may be carbon and the other may be nitrogen. Further, for example, R 2 and R 3 Hydrogen and hydroxyC 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 the groups may be hydrogen and the other may be hydroxy C 1~6 It may be alkyl.

[0060] In this application, the units ul, uMol, C etc. mean μl, μMol, °C etc.

[0061] In this application, R 2 / R 3 and / or R 4 / R 5 In the expression "forming a saturated monocyclic 3- to 5-membered cycloalkyl" the "saturated monocyclic 3- to 5-membered cycloalkyl" is a halogen or haloC 1~6 It means optionally substituted cycloalkyl selected from cyclopropyl, cyclobutyl, and cyclopentyl, which may be optionally substituted with alkyl. In particular, cycloalkyl, such as cyclopropyl, is unsubstituted.

[0062] In this application, R 2 / R 3 and / or R 4 / R 5 In the expression "forming a saturated monocyclic 3- to 6-membered cycloalkyl" the "saturated monocyclic 3- to 6-membered cycloalkyl" is a halogen or haloC 1~6 It means optionally substituted cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, which may be optionally substituted with alkyl. In particular, cycloalkyl, such as cyclopropyl, is unsubstituted.

[0063] In this application, 50 The term "EC" is defined as follows: The agonist effect of a compound can be determined by testing the compound in the in vitro assay described herein, whereby the effect of the compound is measured over a range of compound concentrations. The resulting data is plotted as a concentration-response curve, which typically follows a sigmoidal 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

[0064] The compounds of the present invention may exist in one or more stereoisomeric forms (e.g., they contain one or more asymmetric carbon atoms). Individual stereoisomers (enantiomers and diastereomers) and mixtures thereof are included within the scope of the subject matter disclosed herein. Similarly, it is understood that a compound or salt can exist in tautomeric forms other than those shown in its formula, and 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.

[0065] The compounds of the present invention may contain several asymmetric centers and may exist as optically pure enantiomers, mixtures of enantiomers, e.g. racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereomeric racemates or mixtures of diastereomeric racemates.

[0066] According to the Cahn-Ingold-Prelog rules, the asymmetric carbon atom may be of the "R" or "S" configuration.

[0067] 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 racemates and their enantiomeric components can be performed to separate copolymers and distomers.

[0068] 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.

[0069] "Diastereomer" refers to a stereoisomer that has 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 be separated under high-resolution analytical procedures such as chromatography.

[0070] "Enantiomers" refers to two stereoisomers of a compound which are non-superimposable mirror images of one another.

[0071] The stereochemical definitions and conventions used herein generally follow 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 exist in different stereoisomeric forms. All stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers, and atropisomers, and mixtures thereof, such as racemic mixtures, are intended to form part of the present invention. All organic compounds exist in optically active forms, i.e., they have 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 indicate the sign of rotation of plane polarized light by a compound, with (-) or 1 meaning that 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 one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is called a racemic mixture or racemate, which may occur where there has been no stereoselection or stereospecificity in a chemical reaction or process.

[0072] The terms "racemic mixture" and "racemate" refer to an equimolar mixture of two enantiomeric species, devoid of optical activity.

[0073] 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 rearrangement of some of the bond electrons.

[0074] It is to be understood that the individual enantiomers and diastereomers are included in the table below by compound name, from which their corresponding structures are readily determinable. 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.).

[0075] In some embodiments of the invention, only one of the possible enantiomers is used, while in other embodiments, a mixture of the possible enantiomers with different proportions of each component is used.

[0076] In some embodiments, the compounds of the present invention are isotopically labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically labeled (e.g., radiolabeled) compounds of formula (I') or (I), or solvates or pharma- ceutically acceptable salts thereof, are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into compounds of formula (I') or (I), or solvates or pharma-ceutically acceptable salts thereof, include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, e.g., 2 H, 3 H, 11 C. 13 C. 14C. 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 formula (I') or (I), or solvates or pharma- ceutically acceptable salts thereof, such as 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 may be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0077] 3 H, 11 C. 18 F, 15 O and 13 Substitution with positron emitting isotopes, such as N, can be useful in positron emission tomography (PET) studies to examine 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 processes similar to those described in the Examples set forth below, substituting the appropriate isotopically labeled reagent for the non-isotopically labeled reagent previously used.

[0078] In one embodiment, the present invention provides a pharma- ceutically acceptable salt of a compound of the invention described herein, particularly a pharma- ceutically acceptable salt selected from hydrochloride, fumarate, lactate (particularly derived from L-(+)-lactic acid), tartrate (particularly derived from L-(+)-tartaric acid), and trifluoroacetate. In further particular embodiments, the present invention provides a compound of the invention described herein (i.e., as the "free base" or "free acid", respectively).

[0079] When a bond in a compound formula herein is drawn in a non-stereochemical manner (e.g., flat), 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), the atom to which the stereochemical bond is attached should be understood to be enriched in the absolute stereoisomer shown, unless otherwise stated. In one embodiment, the compound can be at least 51% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 80% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 90% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 95% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 97% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 98% of the absolute stereoisomer depicted. In another embodiment, the compound can be at least 99% of the absolute stereoisomer depicted.

[0080] The term "alkyl" refers to a monovalent or polyvalent, e.g., monovalent or divalent, linear or branched, saturated hydrocarbon group of 1 to 6 carbon atoms, e.g., 1, 2, 3, 4, 5, or 6 carbon atoms ("C 1 - 6 In some embodiments, an alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2, or 3 carbon atoms. Methyl (CH 3 -), ethyl (CH3 CH 2 -), n-propyl (CH 3 CH 2 CH 2 -), 2-propyl (isopropyl, (CH 3 ) 2 CH 2 -), n-butyl (CH 3 CH 2 CH 2 CH 2 -), iso-butyl ((CH 3 ) 2 CH 2 CH 2 -), sec-butyl (CH 3 CH(CH 3 )CH 2 -), and tert-butyl ((CH 3 ) 3 Some non-limiting examples of alkyl are tert-butyl (CH 3 ) 3 C-) or methyl (CH 3 A preferred, but non-limiting example of alkyl is methyl (CH 3 Another preferred, but non-limiting example of alkyl is tert-butyl ((CH 3 ) 3 C-).

[0081] The term "alkoxy" refers to an alkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. An alkoxy group is an alkyl group having 1 to 6 carbon atoms ("C 1 ~ 6 Alkoxy groups include, for example, 1, 2, 3, 4, 5, or 6 carbon atoms. In other embodiments, alkoxy groups contain 1-4 carbon atoms. In yet other embodiments, alkoxy groups contain 1-3 carbon atoms. Some non-limiting examples of alkoxy groups include, CH 3 O-(Methoxy), CH 3 CH 2 O-(ethoxy), CH 3 CH 2 CH 2 O-(n-propoxy), and (CH 3 )3 A particularly preferred, but non-limiting example of alkoxy is methoxy (CH 3 O-).

[0082] As used herein, "C 3~5 Cycloalkyl C 1~6 The term "alkoxy" refers to a group in which at least one of the hydrogen atoms is C 3~5 It refers to an alkoxy group substituted with a cycloalkyl group. 3~5 Cycloalkyl C 1~6 "Alkoxy" means that one, two or three hydrogen atoms of the alkoxy group are C 3~5 It refers to an alkoxy group replaced by a cycloalkyl group. 3~5 Cycloalkyl C 1~6 "Alkoxy" means that one hydrogen atom of the alkoxy group is C 3~5 It refers to an alkoxy group substituted by a cycloalkyl group. Preferably, the alkoxy group contains one C atom. Preferred, but non-limiting examples are 2-cyclopropylmethoxy and 2-cyclobutylmethoxy.

[0083] As used herein, "cyano C 1~6 The term "alkoxy" refers to an alkoxy group in which at least one of the hydrogen atoms is replaced by a cyano group. 1~6 "Alkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkoxy group are replaced by a cyano group. 1~6 "Alkoxy" refers to an alkoxy group in which one hydrogen atom of the alkoxy group is replaced by a cyano group. Preferably, the alkoxy group contains one C atom. In one embodiment, "cyano C 1~6 "Alkoxy" is NC-CH 2 O-, NC-CH 2 CH 2 O-, and NCCH 2 CH 2 CH 2 In a preferred embodiment, cyano C1~6 Alkoxy is NC-CH 2 A preferred, but non-limiting example is NC-CH 2 A preferred example is the structure NC-CH 2 It is 2-cyanomethoxy with O-.

[0084] 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).

[0085] As used herein, the term "cycloalkyl" refers to a monocyclic or polycyclic, saturated or partially unsaturated, non-aromatic 3- to 10-membered monocyclic or polycyclic hydrocarbon group of 3 to 10 ring carbon atoms ("C 3~10In some embodiments, the cycloalkyl group refers to a 4-10 membered cycloalkyl group. In some embodiments, the 4-10 membered cycloalkyl group is monocyclic or bicyclic. In some embodiments, the cycloalkyl group is a saturated monocyclic 3-5 or 4-6 membered hydrocarbon group having 3-5 or 4-6 ring carbon atoms, e.g., 3, 4, or 5 carbon atoms. Or 4, 5, or 6 carbon atoms. In preferred embodiments, the saturated monocyclic 3-6 or 4-6 membered cycloalkyl group is selected from cyclobutyl, cyclopentyl, and cyclohexyl. In some embodiments, the cycloalkyl group contains one or two non-aromatic double bonds. In some embodiments, the cycloalkyl group contains one non-aromatic double bond. In some embodiments, the cycloalkyl group is a monocyclic 4-6 membered cycloalkenyl group having one non-aromatic double bond. In some embodiments, the cycloalkenyl group is selected from cyclobutenyl, cyclopentenyl, and cyclohexenyl. Polycyclic and bicyclic cycloalkyl groups can include fused or bridged polycyclic or bicyclic moieties, each ring being a saturated or partially unsaturated non-aromatic hydrocarbon. Cycloalkyl includes bicyclic cycloalkyl, which refers to a 4-10 membered bridged cycloalkyl moiety consisting of two saturated carbocyclic rings having two carbon atoms in common, i.e., the bridge separating the two rings is either a single bond or a chain of one or two ring atoms. In some embodiments, the cycloalkyl is a 7-10 membered bicyclic edge-to-edge fused cycloalkyl containing two aliphatic rings. In a preferred embodiment, the cycloalkyl is selected from a 4-10 membered bridged cycloalkyl, a saturated monocyclic 3-6 or 4-6 membered cycloalkyl group, a 6 membered cycloalkenyl group, or a 7-10 membered bicyclic fused cycloalkyl. In a particularly preferred embodiment, the cycloalkyl is selected from a 4-10 membered bridged cycloalkyl, a saturated monocyclic 4-6 membered cycloalkyl group, or a 7-10 membered bicyclic fused cycloalkyl. In some examples, the 4- to 10-membered bridged cycloalkyl is selected from bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, and adamantane.In some examples, the 4-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings is selected from bicyclo[3.1.0]hexanyl, octahydropentalenyl, bicyclo[3.2.0]heptanyl, bicyclo[3.2.1]octanyl, bicyclo[3.2.2]octanyl, and hexahydropentalenyl. In some instances, the cycloalkyl does not include bicyclic or polycyclic spirocycloalkyl ring systems. Some non-limiting examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexanyl, bicyclo[3.2.1]octanyl, adamantane, bicyclo[3.2.0]heptanyl, bicyclo[3.2.1]octanyl, and hexahydropentalenyl and octahydropentalene. Other examples can be found in the tables of this application.

[0086] As used herein, "heterocycloalkyl" or "heterocyclyl" refers to a non-aromatic, monocyclic or polycyclic ring system containing carbon and at least one ring heteroatom forming a 5- to 12-membered heterocycloalkyl. Heterocycles are described, for example, in Paquette, Leo A.; "Principles of Modern Heterocyclic Chemistry" (WA Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), especially Volumes 13, 14, 16, 19, and 28, and J. Am. Chem. Soc. (1960) 82:5566. In some embodiments, the heterocycloalkyl is bicyclic. In some embodiments, the heteroatom is independently selected from the group consisting of N, O, and S atoms. In some embodiments, the heteroatom is an O atom. Heterocycloalkyl groups may be saturated or partially unsaturated and, unless otherwise specified, may contain 5, 6, 7, 8, 9, 10, 11, 12 or more ring atoms, where ring atoms refer to the total of carbon atoms and heteroatoms in one or more rings (e.g., 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered heterocycloalkyl). Heterocycloalkyls may contain 1-5 ring heteroatoms, 1-4 heteroatoms, 1-3 ring heteroatoms, 1 or 2 ring heteroatoms, or groups containing 1 ring heteroatom. In some embodiments, one ring atom is an O atom. In some embodiments, heterocycloalkyls are monocyclic 4-6 membered heterocycloalkyls. In some embodiments, a heterocycloalkyl contains 1 ring, 2 rings, 3 rings, 4 rings or more rings, e.g., as a polycyclic fused system, in some embodiments, a heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl containing two aliphatic rings, one of which contains one O atom.In some embodiments, the heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring or two aliphatic rings, where one ring contains one O atom or one N atom, such as dihydrochromenyl. In some embodiments, the bicyclic fused heterocycloalkyl contains one or two non-aromatic double bonds. In some embodiments, the heterocycloalkyl contains one non-aromatic double bond. In some embodiments, the heterocycloalkyl is a 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings, where one ring contains one O atom or one N atom, such as the structure. [ka] or for example a cyclopenta[c]pyrrolyl having the structure [ka] In some embodiments, the heterocycloalkyl includes a 7-10 membered bridged heterosystem, for example, the structure [ka] In some embodiments, the heterocycloalkyl is selected from bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring, where one ring contains one O atom. In some particularly preferred embodiments, the heterocycloalkyl is selected from 5-12 membered heterocycloalkyls, where the heterocycloalkyl is 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyls (wherein the bridge contains an O atom). In some cases, the heterocycloalkyl does not include bicyclic or polycyclic spiroheterocycloalkyl ring systems. Preferred, but non-limiting examples of heterocycloalkyl include oxetanyl, dihydrochromenyl, hexahydrocyclopenta[b]furanyl. Other examples can be found in the tables of this application.

[0087] As used herein, "heterocyclyloxy" refers to a C 4-6 membered heterocycloalkyl group attached to -O- to form an alkoxy group. 1~6 It refers to an alkoxy group. A preferred, yet non-limiting example is oxetanyloxy (specifically oxetan-3-yloxy).

[0088] As used herein, "C 1~6 "Alkyl-6-membered cycloalkenyl" refers to a C6-alkyl group in which a 6-membered heterocycloalkyl group is attached to an alkyl group. 1~6 Preferably, but not limited to, examples are: [ka] It is.

[0089] 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 of carbon atoms and heteroatoms in one 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 N atom and one O atom. Examples of 5-membered heteroaryl groups include, but are not limited to, pyrrolylpyrazolyl, imidazolyl, oxazolyl, triazolyl, or furanyl. In some preferred embodiments, the 5-membered heteroaryl is pyrazolyl, imidazolyl, or oxazolyl. In some more preferred embodiments, the 5-membered heteroaryl is pyrazolyl or imidazolyl. 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.

[0090] The term "cyano" refers to a -CN (nitrile) group.

[0091] The term "oxo" refers to the =0 group.

[0092] The term "hydroxy" or "hydroxyl" refers to an OH group.

[0093] The term "haloalkyl" refers to a C alkyl group having 1 to 6 C atoms. 1~6"Haloalkyl" refers to an alkyl group, in which at least one of the hydrogen atoms of the alkyl group is replaced by one or more halogen atoms. Preferably, "haloalkyl" refers to an alkyl group in which one, two or three hydrogen atoms of the alkyl group are replaced by halogen atoms, i.e., haloalkyl 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" are fluoro (F) and chloro (Cl). More preferably, the haloalkyl is substituted with fluoro (F). As above, the alkyl moiety may be straight or branched chain. Preferred, but non-limiting examples of haloalkyl are (CH 3 ) 2 FC-(1-fluoro-isopropyl), CF 3 CH 2 -(2,2,2-trifluoroethyl), CH 3 CF 2 -(1,1-difluoroethyl), CF 3 -(trifluoromethyl), CH 2 F-(fluoromethyl) or CHF 2 -(difluoromethyl). (CH 3 ) 2 CF-(1-fluoro-isopropyl) is particularly preferred.

[0094] As used herein, "haloalkoxy" refers to a C alkyl group in which at least one of the hydrogen atoms is replaced by a halogen atom. 1~6"haloalkoxy" refers to an alkoxy group. Preferably, "haloalkoxy" refers to an alkoxy group in which one, two, or three hydrogen atoms of the alkyl group are replaced by halogen atoms, i.e., haloalkoxy includes monohaloalkoxy, dihaloalkoxy, trihaloalkoxy, perhaloalkoxy, etc. The halogen atom may 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 haloalkyl is substituted with fluoro (F). The alkyl portion of the haloalkoxy may be linear or branched as described above, and the haloalkoxy has, for example, the following structure: [ka] A preferred, but non-limiting example of haloalkoxy is CHF 2 O-, CH 2 FO-CF 3 CH 2 O-, CF 2 HCH 2 O-, CH 3 CF 2 CH 2 O-, and CH 3 CFHCH 2 O-, CH 3 CF 2 CH 2 O-, CF 3 CH(CH 3 )O-, or FCHCH 2 CHFCH 2 It is O-.

[0095] As used herein, "haloalkylthio" refers to a haloC 1~6"Haloalkylthio" refers to a thio group containing an alkyl group. Preferably, "haloalkylthio" refers to an alkylthio group in which one, two, or three hydrogen atoms of the alkyl group are replaced by halogen atoms, i.e., haloalkylthio includes monohaloalkylthio, dihaloalkylthio, trihaloalkylthio, perhaloalkylthio, etc. The halogen atom may 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 haloalkyl is substituted with fluoro (F). The alkyl portion of the haloalkylthio may be linear or branched as described above. A preferred, but non-limiting example of a haloalkoxy is CHF. 2 S-, CH 2 FS-CF 3 CH 2 S-, CF 2 HCH S -, CH 3 CF 2 CH 2 S-, and CH 3 CFHCH 2 A particularly preferred example has the structure: [ka]

[0096] The term "hydroxyalkyl" refers to a C alkyl group having 1 to 6 C atoms. 1~6 "Hydroxyalkyl" refers to an alkyl group in which at least one of the hydrogen atoms of the alkyl group is replaced by one or more hydroxy. Preferably, "hydroxyalkyl" refers to an alkyl group in which one, two or three hydrogen atoms of the alkyl group are replaced by hydroxy, i.e., hydroxyalkyl includes monohydroxyalkyl, dihydroxyalkyl, trihydroxyalkyl, perhydroxyalkyl, etc. More preferably, "hydroxyalkyl" refers to a C 1 -C 2 -C ... 1~6The alkyl portion of the hydroxyalkyl may be linear or branched as described above. A particularly preferred, but non-limiting example of a hydroxyalkyl is HOCH. 2 -(hydroxymethyl), HOCH(CH 3 )-HOCH 2 CH 2 -(hydroxyethyl), HOCH 2 CH 2 CH 2 -(n-hydroxypropyl) and HOCH 2 CH 2 CH 2 CH 2 -(n-hydroxybutyl).

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

[0098] As used herein, the term "depression" refers 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" refers to a disorder that involves a pattern of disruptive behavior in children that lasts for at least six months and causes problems in school, home and social situations. Behavioral disorders involve a pattern of disruptive behavior in children that lasts for at least six months and causes problems in school, home and 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 excessive activity and impulsivity. ADHD occurs more frequently in epilepsy patients than in the general population. Children with ADHD are at high 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 may begin during the developmental period, affect daily functioning, and may continue 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 developmental disorder of variable severity characterized by difficulties in social interaction and communication, and restricted or repetitive patterns of thought and behavior. ASD encompasses primarily idiopathic but also syndromic 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 "syndromic developmental disorder" refers to a developmental disorder with a clinically defined pattern of somatic abnormalities and a neurobehavioral phenotype that 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 strong 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 the condition include developmental delay, intellectual disability, severe speech disorder, and movement and balance problems (ataxia). Most affected children also have recurrent seizures (epilepsy).

[0107] As used herein, the term "intellectual disability" (ID) relates to a generalized neurodevelopmental disorder characterized by severely impaired intellectual and adaptive functioning. It is defined by an IQ below 70 in addition to multiple adaptive behavioral deficits that affect daily life. ID is also known as general learning disability and was previously known as mental retardation (MR).

[0108] As used herein, the term "epilepsy" 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 widespread childhood epilepsy, West syndrome, Ohtahara syndrome, and epileptic encephalopathy.

[0109] As used herein, the term "neurodegenerative disease" 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] The term "motor neuron disease" as used herein 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] As used herein, the term "pain" refers to the 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] As used herein, the term "migraine" refers to a moderate to severe headache disorder that causes throbbing or throbbing pain for hours or days.

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

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

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

[0116] In all embodiments of the present invention which provide a compound of formula (I) or formula (I′) where n is 0, or a solvate or pharma- ceutically acceptable salt thereof, each carbon atom and each substituent R 4 and R 5 does not exist.

[0117] In some embodiments of the invention that provide a compound of Formula (I) or Formula (I′), or a solvate or pharma- ceutically acceptable salt thereof, R 2 and R 3 together with the carbon atom to which they are attached do not form a saturated monocyclic cycloalkyl as described herein.

[0118] In some embodiments of the present invention that provide a compound of formula (I) or formula (I′) or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 1, the substituent R 4 or R 5 cannot be hydroxy.

[0119] In all embodiments of the present invention that provide a compound of formula (I) or formula (I′) or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 2 or 3, two or three pairs of R 4 / R 5 may be the same or different as described herein.

[0120] The present invention relates to a compound of formula (I'): [ka] Y 1 CR a or N, Y 2 CR b or N, Y 3 CR c or N, (However, Y 1 , Y 2 and Y 3 Only 0 or 1 of is N, and the rest is CR a , C.R. b , or CR c and R a is hydrogen or a halogen, R b is hydrogen or a halogen, R c is hydrogen or a halogen, In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , n and R 6is as described herein, e.g. as described in claim 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0121] In one particularly preferred embodiment, the present invention provides 1 , Y 2 and Y 3 In this embodiment, the compound of formula (I') or a solvate or pharma- ceutically acceptable salt thereof is provided, wherein Y is N. 1 , Y 2 , and Y 3 CR a , C.R. b or CR c In this embodiment, the compound of formula (I') has the structure: [ka] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , n and R 6 are of formula (I) having the formula (I):

[0122] In one embodiment, the present invention provides a method for the preparation of a medicament comprising administering to a subject the 1 , Y 2 , or Y 3 In this embodiment, the present invention provides a compound of formula (I'), or a solvate or pharma- ceutically acceptable salt thereof, wherein one of Y is N. 1 , Y 2 , and Y 3 The others are CR a , C.R. b or CR c It is.

[0123] In one embodiment, the present invention provides a method for the preparation of a medicament comprising administering to a subject the 1 In one embodiment, the compound of formula (I') or a solvate or pharma- ceutically acceptable salt thereof is provided, wherein only Y 2 and Y 3 CRb or CR c It is.

[0124] In one embodiment, the present invention provides a method for the preparation of a medicament comprising administering to a subject the 2 In one embodiment, the compound of formula (I') or a solvate or pharma- ceutically acceptable salt thereof is provided, wherein only Y 1 and Y 3 CR a or CR c It is.

[0125] In one embodiment, the present invention provides a method for the preparation of a medicament comprising administering to a subject the 3 In one embodiment, the compound of formula (I') or a solvate or pharma- ceutically acceptable salt thereof is provided, wherein only Y 1 and Y 2 CR a or CR b It is.

[0126] The present invention includes the following compounds: [Table 1]

[0127] Y 1 , Y 2 and Y 3 All of the features and embodiments disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the 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.

[0128] In one embodiment, the present invention relates to a compound of formula (I*): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 independently selected from alkyl and hydroxy; R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; R 7 is a halogen, m is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0129] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, HaloC 1~6 Alkylthio, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl is one C 1~6 Alkyl or haloC 1~6 The 4- to 6-membered cycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, and haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl, Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 Alkyl, C 2~6 optionally substituted with 1, 2 or 3 substituents independently selected from alkynyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0130] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 The 4- to 6-membered cycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, haloC 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl, Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 Alkyl, C 2~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkynylalkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0131] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl-6-membered cycloalkenyl, C 1~6 Alkyl, Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl, cycloalkenyl, or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, hydroxy, oxo and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0132] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 independently selected from alkyl, hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, hydroxy, hydroxyC 1~6 Alkyl and halo 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0133] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, haloC 1~6 Alkoxy, HaloC 1~6 Alkylthio, 4-6 membered heterocyclyloxy, halogen, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0134] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0135] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkyl, haloC 1~6 Alkoxy and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 independently selected from alkyl and hydroxy; R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0136] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 independently selected from alkoxy, and hydroxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0137] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0138] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, haloC 1~6 Alkoxy, HaloC 1~6 Alkylthio, 4-6 membered heterocyclyloxy, halogen, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0139] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, 4-6 membered heterocyclyloxy, halogen, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and halo 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0140] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 O-, HaloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkoxy, cyano, and hydroxy; n is 0, 1, 2 or 3; however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0141] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] TIFF2024542881000034.tif145165 or a solvate or pharma- ceutically acceptable salt thereof.

[0142] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; however, [ka] TIFF2024542881000037.tif53165 or a solvate or pharma- ceutically acceptable salt thereof.

[0143] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, CHF 2 O-, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0144] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, CHF 2 O-, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 Alkyl, haloC 1~6 Alkyl, haloC 1~6 alkoxy, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , HaroC 1~6 Alkoxy and HaloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2 or 3; (however, [ka] TIFF2024542881000041.tif214165 or a solvate or pharma- ceutically acceptable salt thereof.

[0145] In some embodiments of the present invention, R 2 and R 3 do not, together with the carbon atom to which they are attached, form a saturated monocyclic 3- to 5-membered cycloalkyl.

[0146] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy, and C 1~6 independently selected from alkoxy, or R 4 and R5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , and Halo C 1~6 alkoxy, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0147] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, a Si(C 1~6 Alkyl) 3 , and Halo C 1~6 alkoxy, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0148] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, haloC 1~6 Alkylthio, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, heterocyclyloxy, or heteroaryl are each independently selected from the group consisting of one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 3- to 10-membered cycloalkyl selected from a saturated monocyclic 4- to 6-membered cycloalkyl, a 6-membered cycloalkenyl, a 4- to 10-membered bridged cycloalkyl, and a 7- to 10-membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, HaloC 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0149] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, heterocyclyloxy, or heteroaryl are each independently selected from the group consisting of one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0150] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, heterocyclyloxy, or heteroaryl are each independently selected from the group consisting of one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0151] In some preferred embodiments, n is 0 or 1.

[0152] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, heterocyclyloxy, or heteroaryl are each independently selected from the group consisting of one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, or 2; (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0153] In some embodiments, n is 0 or 1.

[0154] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0155] In some preferred embodiments, n is 0 or 1.

[0156] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0157] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; Bicyclic edge-fused heterocycloalkyl, 7- to 10-membered bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, or bicyclic edge-fused cycloalkyl is preferably selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, and hydroxyC 1~6 Alkyl, haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0158] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; Bicyclic edge-fused heterocycloalkyl, 7- to 10-membered bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, or bicyclic edge-fused cycloalkyl is preferably selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, and hydroxyC 1~6 Alkyl, haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0159] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; Bicyclic edge-fused heterocycloalkyl, bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, or bicyclic edge-fused cycloalkyl is not limited to Cl-, F-, CH 3 - and CF 3 -, and n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0160] In some preferred embodiments, n is 0 or 1.

[0161] In some particularly preferred embodiments, R 6 is substituted with two F-.

[0162] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 7-10 membered bridged heterocycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, 4-10 membered bridged cycloalkyls, 7-10 membered fused cycloalkyls, tert-butyl, (CH 3 ) 2 CF-, 6-membered heteroaryl, wherein bicyclic fused heterocycloalkyl, bridged heterocycloalkyl, saturated monocyclic cycloalkyl, bridged cycloalkyl, phenyl, fused cycloalkyl or 6-membered heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000057.tif55165 or a solvate or pharma- ceutically acceptable salt thereof.

[0163] In some preferred embodiments, n is 0 or 1.

[0164] In some preferred embodiments, R 6 is a halogen, C 1~6 Alkyl and halo 1~6 Substituted with 1 or 2 substituents independently selected from alkyl.

[0165] In some preferred embodiments, R 6 are Cl-, F-, and CH 3 - and CF 3 - is substituted with 1 or 2 substituents independently selected from:

[0166] In some preferred embodiments, R 6 is substituted with two F-. In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 7-10 membered bridged heterocycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, 4-10 membered bridged cycloalkyls, 7-10 membered fused cycloalkyls, tert-butyl, (CH 3 ) 2 CF-, and 6-membered heteroaryl, wherein the bicyclic fused heterocycloalkyl, bridged heterocycloalkyl, saturated monocyclic cycloalkyl, bridged cycloalkyl, phenyl, fused cycloalkyl or 6-membered heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000060.tif230165 or a solvate or pharma- ceutically acceptable salt thereof.

[0167] In some embodiments, n is 0 or 1.

[0168] . In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, CHF 2 O-, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6are 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 7-10 membered bridged heterocycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, 4-10 membered bridged cycloalkyls, 7-10 membered fused cycloalkyls, tert-butyl, (CH 3 ) 2 CF-, 6-membered heteroaryl, wherein bicyclic fused heterocycloalkyl, bridged heterocycloalkyl, saturated monocyclic cycloalkyl, bridged cycloalkyl, phenyl, fused cycloalkyl or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000063.tif173165 or a solvate or pharma- ceutically acceptable salt thereof.

[0169] In some embodiments, n is 0 or 1.

[0170] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, CHF 2O-, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 7-10 membered bridged heterocycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, 4-10 membered bridged cycloalkyls, 7-10 membered fused cycloalkyls, tert-butyl, (CH 3 ) 2 CF-, 6-membered heteroaryl, wherein bicyclic fused heterocycloalkyl, bridged heterocycloalkyl, saturated monocyclic cycloalkyl, bridged cycloalkyl, phenyl, fused cycloalkyl or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000066.tif141165 excluded), or a solvate or pharma- ceutically acceptable salt thereof.

[0171] In some embodiments, n is 0 or 1.

[0172] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyridinyl and pyrimidinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyridinyl or pyrimidinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2, or a solvate or pharma- ceutically acceptable salt thereof.

[0173] In some preferred embodiments, n is 0 or 1.

[0174] In some embodiments, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl.

[0175] In some preferred embodiments, R 6 is a halogen, C 1~6 Alkyl and halo 1~6 Substituted with 1 or 2 substituents independently selected from alkyl.

[0176] In some preferred embodiments, R 6 are Cl-, F-, and CH 3 - and CF 3 - is substituted with 1 or 2 substituents independently selected from:

[0177] In some preferred embodiments, R 6 is substituted with two F-.

[0178] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyridinyl and pyrimidinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyridinyl or pyrimidinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0179] In some embodiments, n is 0 or 1.

[0180] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, hydroxy, and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0181] In some embodiments, n is 0 or 1.

[0182] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl; heterocycloalkyl, heterocyclyloxy, C 3~5 Cycloalkyl C 1~6 Alkoxy or heteroaryl may be one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000074.tif145165 or a solvate or pharma- ceutically acceptable salt thereof.

[0183] In some embodiments, n is 0 or 1.

[0184] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000077.tif81165 or a solvate or pharma- ceutically acceptable salt thereof.

[0185] In some embodiments, n is 0 or 1.

[0186] In one embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, CHF 2 O-, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6Alkoxy and Cyano C 1~6 alkoxy, heterocycloalkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy or heterocyclyloxy is a heterocyclic group having one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, C 1~6 Alkyl, and hydroxy C 1~6 independently selected from alkyl and hydroxy; R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, and C 1~6 independently selected from alkoxy, or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1 or 2; (however, [ka] TIFF2024542881000080.tif230165 or a solvate or pharma- ceutically acceptable salt thereof.

[0187] In some embodiments, n is 0 or 1.

[0188] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, or a pharmaceutical composition comprising such a compound, or a solvate or pharma- ceutically acceptable salt thereof: [ka] (In the formula, R 1 is HaroC 1~6 is an alkoxy; R2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, haloC 1~6 independently selected from alkyl, R 6 is a 3-10 membered cycloalkyl and haloC 1~6 alkyl, (n is 1).

[0189] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, or a pharmaceutical composition comprising such a compound, or a solvate or pharma- ceutically acceptable salt thereof: [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl, heterocycloalkyl, heterocyclyloxy and heteroaryl are selected from one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy, Hydroxy C 1~6 independently selected from alkyl and hydroxy; R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; where n is 0, 1, 2 or 3.

[0190] or a pharmaceutical composition comprising a compound selected from the list below, or a solvate or pharma- ceutically acceptable salt thereof: [Table 2] TIFF2024542881000084.tif245170 TIFF2024542881000085.tif167165

[0191] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, or a pharmaceutical composition comprising such a compound, or a solvate or pharma- ceutically acceptable salt thereof: [ka] (In the formula, Y 1 , Y 2 and Y 3 are each independently selected from CH or N; However, Y 1 , Y 2 and Y 3 Only 0 or 1 in is N, R 1 is HaroC 1~6 Alkoxy, HaloC 1~6 alkylthio, 4- to 6-membered cycloalkyloxy (wherein the 4- to 6-membered cycloalkyloxy may be optionally substituted with 1, 2, or 3 substituents independently selected from halogen); 1~6 Alkoxy is C 1~6 optionally substituted with alkoxy; R 2 and R 3 are independently selected from hydrogen; R 4 and R 5 is hydrogen, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, and haloC 1~6 independently selected from alkyl, R 6 is 3 to 10 membered cycloalkyl, phenyl, haloC 1~6 Alkyl, haloC 1~6 Alkoxy, and TriC 1~6 alkylsilyl, cycloalkyl or phenyl is selected from halogen, haloC 1~6 Alkoxy and HaloC 1~6 Alkyl, C 2~6 optionally substituted with 1, 2 or 3 substituents independently selected from alkynyl; where n is 0, 1 or 2.

[0192] Some of the preferred embodiments of the present invention are represented by formula (I): [ka] (In the formula, R 1 is 4-6 membered heterocycloalkyl, cyano, haloC 1~6 Alkoxy, C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy, Cyano C 1~6 alkoxy and 5-membered heteroaryl, heterocycloalkyl, heterocyclyloxy and heteroaryl are selected from one C 1~6 Alkyl or haloC 1~6 optionally substituted with alkyl; R 2 and R 3 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and Hydroxy C 1~6 independently selected from alkyl, R 2 and R 3 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 4 and R 5 is hydrogen, deuterium, C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, C 1~6 Alkoxy and hydroxy C 1~6 alkyl, and hydroxy; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, a phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; n is 0, 1, 2, or 3, or a solvate or pharma- ceutically acceptable salt thereof.

[0193] Some of the preferred embodiments of the present invention are 1 But Cyano, Halo C 1~6 Alkoxy, 4-6 membered heterocyclyloxy, halogen, haloC 1~6 Alkyl, C 3~5 Cycloalkyl C 1~6 Alkoxy and cyano C 1~6 alkoxy, heterocyclyloxy or cycloalkylalkoxy selected from one C 1~6 Alkyl or haloC 1~6 This includes compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, which may be optionally substituted with alkyl.

[0194] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano, Halo C 1~6 Alkoxy and haloC 1~6 is selected from alkyl.

[0195] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 , cyano, CHF 2 O-, CH 3 CF 2 O-, CH 3 CFHCH 2 O-, CF 3 CH 2 O-, CH 3 CF 2-, CHF 2 - and CF 3 It is.

[0196] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O-, CH 3 CF 2 O-, CH 3 CFHCH 2 O-, and CF 3 CH 2 It is O-.

[0197] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O- or CH 3 CF 2 It is O-.

[0198] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 It is O-.

[0199] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is halogen and haloC 1~6 and 5-membered heteroaryl selected from pyrazolyl and imidazolyl optionally substituted with 1, 2 or 3 substituents independently selected from alkyl.

[0200] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is unsubstituted pyrazolyl or unsubstituted imidazolyl.

[0201] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein: (i) R 2 and R 3 are both hydrogen, or (ii) R 2 and R 3 One of them is hydrogen and the other is hydroxy C 1~6 It is an alkyl.

[0202] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 2 and R 3 One is hydrogen and the other is HOCH 2 -HOCH 2 CH 2 -HOCH 2 CH 2 CH 2 - and HOCH 2 CH 2 CH 2 CH 2 -Hydroxy C selected from 1~6 It is an alkyl.

[0203] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, comprising hydroxy C 1~6 Alkyl is HOCH 2 - or HOCH 2 CH 2 -It is.

[0204] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 2 and R 3 are both hydrogen.

[0205] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 0 or 1.

[0206] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 0.

[0207] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 1.

[0208] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 1, and (i) 4 and R 5 are hydrogen, and (ii) R 4 and R 5 One of them is hydrogen and the other is C 1~6 Alkyl, saturated monocyclic 3-5 membered cycloalkyl, or C 1~6 It is an alkoxy.

[0209] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 4 and R 5 One of them is hydrogen and the other is methyl (CH 3 -) or methoxy (CH 3 O-).

[0210] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein saturated monocyclic 3-5 membered cycloalkyl is unsubstituted cyclopropyl.

[0211] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein n is 1 and R 4 and R 5 are both hydrogen.

[0212] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 4 and R 5 together with the carbon atom to which they are attached form a cyclopropyl.

[0213] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, C 1~6 Alkyl, haloC 1~6 alkyl, and phenyl, wherein heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0214] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is selected from 5- to 12-membered heterocycloalkyl, 6-membered heteroaryl, and 4- to 10-membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0215] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 6 are Cl-, F-, and CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0216] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 6 are Cl-, F-, and CH 3 -, CF 3 -, cyclopropyl, and CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-.

[0217] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 6 are Cl-, F-, and CH 3 - and CF 3 -, optionally substituted with 1, 2 or 3 substituents independently selected from:

[0218] Some of the preferred embodiments of the present invention are 6 but, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C 1~6 Alkyl; and e) Halo C 1~6 alkyl, which includes the compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, optionally substituted as described herein.

[0219] Some of the preferred embodiments of the present invention are 6 but, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; which includes the compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, optionally substituted as described herein.

[0220] Some of the preferred embodiments of the present invention are 6 but, Dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, which include the compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, optionally substituted as described herein.

[0221] Some of the preferred embodiments of the present invention are 6 but, and selected from dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, which may be optionally substituted as described herein, including the compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof.

[0222] Some of the preferred embodiments of the present invention are 6 but, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0223] Some particularly preferred embodiments include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is substituted with 1 or 2 F- as described herein, R 6 teeth, [ka] is selected from.

[0224] Some particularly preferred embodiments include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is substituted with 1 or 2 F- as described herein, R 6 teeth, [ka] is selected from.

[0225] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O-, unsubstituted pyrazolyl, unsubstituted imidazolyl, CH 3 O-, (CH 3 )CF 2 -, CN-, CHF 2 -, CF 3 -, CF 3 CH 2 O-, CH 3 CFHCH 2 O-, R 2 and R 3 is hydrogen, n is 0 or 1, (i) R 4 and R 5 is hydrogen, or (ii) R 4 and R 5is hydrogen and the other is cyclopropyl, or (iii) R 4 and R 5 together with the carbon atom to which they are attached form a cyclopropyl group, and R 6 is selected from 5-12 membered heterocycloalkyl (wherein the heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom), a 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (one ring containing one O atom or one N atom), a 7-10 membered bridged heterosystem (the bridge contains an O atom)), a 6 membered heteroaryl, and a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings, any of which may be optionally substituted as described herein.

[0226] Some preferred embodiments of the present invention include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, as described herein, wherein R 1 is CHF 2 O- or unsubstituted imidazolyl; R 2 and R 3 is hydrogen, n is 0 or 1, (i) R 4 and R 5 is hydrogen, or (ii) R 4 and R 5 is hydrogen and the other is cyclopropyl, or (iii) R 4 and R 5 together with the carbon atom to which they are attached form a cyclopropyl group, R 6is selected from 5-12 membered heterocycloalkyl (heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom)), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two rings (one ring containing one O atom or one N atom), 7-10 membered bridged heterosystem (the bridge contains an O atom), 6 membered heteroaryl, and 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, 4-10 membered bridged cycloalkyl, and 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings, any of which may be optionally substituted as described herein.

[0227] Some preferred embodiments of the present invention, according to claim 37, comprise a compound of formula (I) or a solvate or a pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O- or unsubstituted imidazolyl; R 2 and R 3 is hydrogen, n is 0, and R 6 is selected from 5-12 membered heterocycloalkyl (heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom)), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two rings (one ring containing one O atom or one N atom), 7-10 membered bridged heterosystem (the bridge contains an O atom), 6 membered heteroaryl, and 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, 4-10 membered bridged cycloalkyl, and 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings, any of which may be optionally substituted as described herein.

[0228] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O- and R 6is one or two Cl-, F-, CH 3 - and CF 3 - which may be optionally substituted.

[0229] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O- and R 6 1 or 2 F- or CF 3 - which may be optionally substituted.

[0230] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is CHF 2 O-, n is 0 or 1, and R 6 is selected from 5- to 12-membered heterocycloalkyl, 6-membered heteroaryl, and 4- to 10-membered cycloalkyl, wherein the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from one or two F- or CF 3 - which may be optionally substituted.

[0231] Some preferred embodiments of the present invention include compounds of formula (I) as described herein, or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is CHF 2 O-, n is 0 or 1, and R 6 is selected from 5- to 12-membered heterocycloalkyl, 6-membered heteroaryl, and 4- to 10-membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from 1 or 2 CF 3 - which may be optionally substituted.

[0232] Some preferred embodiments include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 O- or unsubstituted imidazolyl; R2 and R 3 is hydrogen, n is 0, and R 6 are 7-10 membered bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 7-10 membered bridged heterocycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, 4-10 membered bridged cycloalkyls, 7-10 membered fused cycloalkyls, tert-butyl, (CH 3 ) 2 CF-, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclic fused heterocycloalkyl, bridged heterocycloalkyl, saturated monocyclic cycloalkyl, bridged cycloalkyl, phenyl, fused cycloalkyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from one CF 3 - which may be optionally substituted.

[0233] In some preferred embodiments, R 6 is, as described herein, 3 and R 6 is substituted with one other substituent of

[0234] In some preferred embodiments, R 6 The other substituents of R are hydroxy and R 6 has the following structure: [ka]

[0235] Some particularly preferred embodiments include compounds of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 6 is a single CF 3 - is replaced by R 6 is selected from: [ka]

[0236] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkoxy, C 1~6 Alkoxy, halo 1~6 selected from alkyl and 5-membered unsubstituted heteroaryl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 are bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 4-10 membered bridged cycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, (CH 3 ) 2 CF-, and 6-membered heteroaryl, wherein the bicyclic fused heterocycloalkyl, bridged cycloalkyl, cycloalkyl, phenyl, or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl. n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0237] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkoxy, C 1~6 Alkoxy, halo 1~6 selected from alkyl and 5-membered unsubstituted heteroaryl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 is selected from bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (one ring containing one O atom or one N atom), 4-10 membered bridged cycloalkyl, saturated monocyclic 4-6 membered cycloalkyl, phenyl, and 6 membered heteroaryl, wherein the bicyclic fused heterocycloalkyl, bridged cycloalkyl, cycloalkyl, phenyl, or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl. n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0238] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkoxy, C 1~6 Alkoxy, halo 1~6selected from alkyl and 5-membered unsubstituted heteroaryl; R 2 and R 3 is hydrogen, or R 4 and R 5 is hydrogen, R 6 are bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 4-10 membered bridged cycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, (CH 3 ) 2 CF-, and 6-membered heteroaryl, wherein the bicyclic fused heterocycloalkyl, bridged cycloalkyl, cycloalkyl, phenyl, or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl. n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0239] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkoxy, C 1~6 Alkoxy, halo 1~6selected from alkyl and 5-membered unsubstituted heteroaryl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 are bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 4-10 membered bridged cycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, (CH 3 ) 2 CF-, and 6-membered heteroaryl, wherein the bicyclic fused heterocycloalkyl, bridged cycloalkyl, cycloalkyl, phenyl, or heteroaryl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl. n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0240] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 Cyano, Halo C 1~6 Alkoxy, C 1~6 Alkoxy, halo 1~6selected from alkyl and 5-membered unsubstituted heteroaryl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and is selected from dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl, or pyridinyl is not Cl-, F-, or CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0241] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 , cyano, CHF 2 O-, CH 3 CF 2 -, CH 3 O-, CH 3 CFHCH 2 O-, CF 3 CH 2 O-, CH 3 CF 2 -, CHF 2 -, CF 3 -, unsubstituted pyrazolyl and unsubstituted imidazolyl, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 are bicyclic edge-fused heterocycloalkyls containing one aliphatic ring and one aromatic ring (each ring containing one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyls containing two aliphatic rings (each ring containing one O atom or one N atom), 4-10 membered bridged cycloalkyls, saturated monocyclic 4-6 membered cycloalkyls, phenyl, (CH 3 ) 2 CF-, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclic fused heterocycloalkyl, bridged cycloalkyl, cycloalkyl, phenyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy. n is 0 or 1, (however, [ka] TIFF2024542881000103.tif55165 or a solvate or pharma- ceutically acceptable salt thereof.

[0242] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 , cyano, CHF 2 O-, CH 3 CF 2 -, CH 3 O-, CH 3 CFHCH 2 O-, CF 3 CH 2 O-, CH 3 CF 2 -, CHF 2 -, CF 3 -, unsubstituted pyrazolyl and unsubstituted imidazolyl, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1, (however, [ka] TIFF2024542881000106.tif150165 or a solvate or pharma- ceutically acceptable salt thereof.

[0243] In a preferred embodiment, the present invention provides a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, CH 3 CF2 O-, CH 3 CFHCH 2 O-, CF 3 CH 2 O-, pyrazolyl and imidazolyl, wherein pyrazolyl and imidazolyl are unsubstituted or selected from one CF 3 -, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0244] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, CH 3 CF 2 O-, CH 3 CFHCH 2 O-, and CF 3 CH 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0245] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, CH 3 CF 2 O-, CH 3 CFHCH 2 O-, and CF 3 CH 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1, (however, [ka] TIFF2024542881000112.tif236165 TIFF2024542881000113.tif169165 or a solvate or pharma- ceutically acceptable salt thereof.

[0246] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O- or unsubstituted imidazolyl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0247] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O- or unsubstituted imidazolyl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0248] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from CCl-, F-CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy; n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0249] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0250] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is unsubstituted imidazolyl, or CH 3 CF 2 -, CF 3 -, CH 2 F, and CHF 2 -, wherein the imidazolyl is substituted with one substituent selected from R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, or R 4 and R 5 together with the carbon atom to which they are attached form an unsubstituted cyclopropyl; R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0251] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O- or unsubstituted imidazolyl; R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0252] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O- or unsubstituted imidazolyl; R2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, and pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl, or pyridinyl is selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0253] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R6 is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl and pyridinyl, selected from bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl or pyridinyl, selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0254] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is CHF 2 O-, R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl and pyridinyl, selected from bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl or pyridinyl, selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1), or a solvate or pharma- ceutically acceptable salt thereof.

[0255] In a particularly preferred embodiment, the present invention relates to a compound of formula (I): [ka] (In the formula, R 1 is unsubstituted imidazolyl, or CH 3 CF 2 -, CF 3 -, CH 2 F, and CHF 2 -, wherein the imidazolyl is substituted with one substituent selected from R 2 and R 3 is hydrogen, R 4 and R 5 is hydrogen, R 6is selected from bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexenyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, pyrazinyl, pyrimidinyl and pyridinyl, and bicyclo[1.1.1]pentanyl, cyclopentyl, cyclohexyl, cyclobutyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, bicyclo[1.1.1]pentanyl and bicyclo[2.2.2]octanyl are selected from Cl-, F-, CH 3 - and CF 3 -, n is 0 or 1, (however, [ka] or a solvate or pharma- ceutically acceptable salt thereof.

[0256] It should be understood that features, integers, characteristics, compounds, chemical moieties or groups described in connection with a particular aspect, embodiment or example of the invention are applicable to any other aspect, embodiment or example described herein, except where incompatible therewith. All of the features disclosed herein (including any accompanying claims, abstracts and drawings), and / or all of the 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 formula (I), or a solvate or pharma-ceutically acceptable salt thereof, may be combined with any embodiment of a pharmaceutical composition, a kit, a medical use or a method of treatment. The invention extends to any novel or any novel combination of features disclosed herein (including any accompanying claims, abstracts and drawings), or any novel or any novel combination of steps of any method or process so disclosed.

[0257] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl.

[0258] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl, which is a 5-membered monocyclic aromatic group having two N atoms.

[0259] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl, which is a 5-membered monocyclic aromatic group containing one N atom and one O atom.

[0260] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 is 5-12 membered heterocycloalkyl, 6 membered heteroaryl, 4-10 membered cycloalkyl, phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0261] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 is selected from 5-12 membered heterocycloalkyl, 6 membered heteroaryl, and 4-10 membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0262] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C 1~6 Alkyl; and f) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, a cycloalkenyl, a bridged cycloalkyl, a bicyclic edge-fused cycloalkyl, or a phenyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0263] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0264] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3 -, cyclopropyl, CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0265] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl; R 6 is selected from dihydrochromenyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl; Chromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl, or pyridinyl is not an alkyl radical, Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3 -, cyclopropyl, CH3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0266] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein the 5-membered heteroaryl is selected from pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, triazolyl, and furanyl.

[0267] In one preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein 5-membered heteroaryl is selected from pyrazolyl, imidazolyl, and oxazolyl.

[0268] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein the 5-membered heteroaryl is selected from pyrazolyl or imidazolyl, wherein pyrazolyl or imidazolyl is C 1~6 Alkyl or haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0269] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein the 5-membered heteroaryl is selected from pyrazolyl and imidazolyl, and the pyrazolyl or imidazolyl is selected from one C 1~6 Alkyl or haloC 1~6 It may be optionally substituted with alkyl.

[0270] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is unsubstituted pyrazolyl.

[0271] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 1, 2, or 3 halo C 1~6 It is selected from alkyl substituted pyrazolyl and imidazolyl.

[0272] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is (CH 3 ) 2 CF-, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 -One halo selected from 1~6 It is an alkyl substituted pyrazolyl.

[0273] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CF 3 -substituted pyrazolyl.

[0274] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one C 1~6 It is an alkyl substituted pyrazolyl.

[0275] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CH 3 -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, sec-butyl, and tert-butyl; 1~6 It is an alkyl substituted pyrazolyl.

[0276] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CH 3 -substituted pyrazolyl.

[0277] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 can have 1, 2, or 3 C's 1~6 Alkyl or haloC 1~6 It is an imidazolyl substituted with alkyl.

[0278] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is unsubstituted imidazolyl.

[0279] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one halo C 1~6 It is an imidazolyl substituted with alkyl.

[0280] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is (CH 3 ) 2 CF-, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 -One halo selected from 1~6 It is an imidazolyl substituted with alkyl.

[0281] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CF 3 -substituted imidazolyl.

[0282] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one C 1~6 It is an imidazolyl substituted with alkyl.

[0283] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CH 3 one C selected from -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, and tert-butyl; 1~6 It is an imidazolyl substituted with alkyl.

[0284] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CH 3 -substituted imidazolyl.

[0285] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 can have 1, 2, or 3 C's 1~6 Alkyl or haloC 1~6 and oxazolyl optionally substituted with alkyl.

[0286] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is unsubstituted oxazolyl.

[0287] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one halo C 1~6 It is an oxazolyl substituted with alkyl.

[0288] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is (CH 3 ) 2 CF-, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 -One halo selected from 1~6 It is an oxazolyl substituted with alkyl.

[0289] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CF 3 -substituted oxazolyl.

[0290] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one C 1~6 -alkyl substituted oxazolyl.

[0291] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CH 3 one C selected from -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, and tert-butyl; 1~6 It is an oxazolyl substituted with alkyl.

[0292] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one CH 3 -substituted oxazolyl.

[0293] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, imidazolyl, or oxazolyl, which is unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen.

[0294] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, and oxazolyl, where pyrazolyl, imidazolyl, or oxazolyl is unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen and n is 0, 1, or 2.

[0295] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, and oxazolyl, where pyrazolyl, imidazolyl, or oxazolyl is unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1 or 2, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom), a saturated monocyclic 4-6 membered cycloalkyl, a phenyl or a 4-10 membered bridged cycloalkyl, wherein the fused heterocycloalkyl, saturated monocyclic cycloalkyl, phenyl or bridged cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0296] In embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0297] In some preferred embodiments, n is 0 or 1.

[0298] In some embodiments, the compound of formula (I) is [ka] isn't it.

[0299] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0300] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl or imidazolyl, which is unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a bicyclic edge-fused heterocycloalkyl, saturated monocyclic 4-6 membered cycloalkyl, or 4-10 membered bridged cycloalkyl containing one aliphatic ring and one aromatic ring (one ring containing one O atom), and the fused heterocycloalkyl, saturated monocyclic cycloalkyl, phenyl, or bridged cycloalkyl may be selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0301] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0302] In some embodiments of the compound of Formula (I), wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 and optionally substituted with 1, 2, or 3 substituents independently selected from alkyl, and the compound is not: [ka]

[0303] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0304] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, which is substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0305] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted 4-10 membered bridged cycloalkyl.

[0306] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0307] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R3 , R 4 , R 5 、 and R 6 is as described herein, and non-limiting examples are selected from: [Table 3]

[0308] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a monocyclic 4- to 6-membered cycloalkenyl group having one non-aromatic double bond, which is 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0309] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is an unsubstituted monocyclic 4- to 6-membered cycloalkenyl group having one non-aromatic double bond.

[0310] In some embodiments, n is 1 or 2, and R 4 and R 5 are both hydrogen.

[0311] In some preferred embodiments, n is 0 or 1.

[0312] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 2, and R 4 and R 5 is hydrogen, and R 6 is a monocyclic 4- to 6-membered cycloalkenyl group having one non-aromatic double bond, which is 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0313] R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 2, and R 4 and R 5 is hydrogen and R 6 In some embodiments, where R is a monocyclic 4-6 membered cycloalkenyl group having one non-aromatic double bond, the compound of Formula (I) is not: [ka]

[0314] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0315] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 2, and R 4 and R 5 is hydrogen, and R 6 is an unsubstituted monocyclic 4- to 6-membered cycloalkenyl group selected from cyclobutenyl, cyclopentenyl, and cyclohexenyl.

[0316] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 2, and R 4 and R 5 is hydrogen, and R 6 is unsubstituted cyclohexyl.

[0317] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 4]

[0318] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3is hydrogen, n is 0, 1, or 2, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, the fused heterocycloalkyl being unsubstituted or substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 Substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0319] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, the fused heterocycloalkyl being unsubstituted or containing one, two, or three halogen or haloC 1~6 It is substituted with alkyl.

[0320] In some embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0321] In some preferred embodiments, n is 0 or 1.

[0322] In some embodiments, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, the fused heterocycloalkyl being unsubstituted or containing one, two, or three halogen or haloC 1~6 is substituted with alkyl and the compound is not: [ka]

[0323] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0324] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, the fused heterocycloalkyl being unsubstituted or containing one, two, or three halogen or haloC 1~6 It is substituted with alkyl.

[0325] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, the fused heterocycloalkyl being unsubstituted or containing one halogen or haloC 1~6 It is substituted with alkyl.

[0326] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom, and the fused heterocycloalkyl is 3 - and CF 3 - which may be optionally substituted.

[0327] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring, one ring containing one O atom.

[0328] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted dihydrochromenyl.

[0329] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 teeth, [ka] It is.

[0330] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 5]

[0331] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0332] In some embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0333] In some preferred embodiments, n is 0 or 1.

[0334] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being selected from halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0335] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being one halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with alkyl.

[0336] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6is a 4-10 membered bridged cycloalkyl, which is unsubstituted or contains one Cl-, F-, CH 3 - and CF 3 - has been replaced.

[0337] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl.

[0338] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[1.1.1]pentanyl.

[0339] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 teeth, [ka] It is.

[0340] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 6]

[0341] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0342] In some embodiments, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 and optionally substituted with 1, 2, or 3 substituents independently selected from alkyl, and the compound is not: [ka]

[0343] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0344] In some embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0345] In some preferred embodiments, n is 0 or 1.

[0346] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is selected from the group consisting of halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0347] In some embodiments, the saturated monocyclic 4-6 membered cycloalkyl is unsubstituted.

[0348] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or 3 one C selected from -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, and tert-butyl; 1~6 It is substituted with alkyl.

[0349] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or contains one CH 3 - has been replaced.

[0350] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is selected from cyclobutyl, cyclopentyl, and cyclohexyl, where the cyclobutyl, cyclopentyl, or cyclohexyl is unsubstituted or contains one CH 3 - has been replaced.

[0351] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted cyclobutyl, cyclopentyl, or cyclohexyl.

[0352] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted cyclobutyl or unsubstituted cyclopentyl.

[0353] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted cyclopentyl.

[0354] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 7]

[0355] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 and phenyl optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0356] In some embodiments, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, haloC 1~6 Alkyl and haloC 1~6 and phenyl optionally substituted with 1, 2 or 3 substituents independently selected from alkyl, and the compound is not: [ka]

[0357] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0358] In some embodiments, R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3is hydrogen, n is 0, 1, or 2, and R 6 is a halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, haloC 1~6 Alkyl and haloC 1~6 Phenyl optionally substituted with 1, 2 or 3 substituents independently selected from alkyl, for medical uses, kits, or pharmaceutical compositions only.

[0359] In some embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0360] In some preferred embodiments, n is 0 or 1.

[0361] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted or halogen, C 1~6 Alkyl and haloC 1~6 and phenyl optionally substituted with 1, 2 or 3 substituents independently selected from alkyl.

[0362] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted or halogen, C 1~6 Alkyl and haloC 1~6and phenyl optionally substituted with one substituent selected from alkyl.

[0363] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is phenyl substituted with one halogen.

[0364] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is phenyl substituted with one halogen selected from F-, Cl-, or Br-.

[0365] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is phenyl substituted with one Cl-.

[0366] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is pyrazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6is as described herein, and a non-limiting example has the structure: [Table 8]

[0367] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 4 and R 5 is hydrogen and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl or a 4- to 10-membered bridged cycloalkyl, and the saturated monocyclic cycloalkyl or bridged cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0368] In some embodiments, n is 1 or 2, and R 4 and R 5 is hydrogen.

[0369] In some preferred embodiments, n is 0 or 1.

[0370] In some embodiments, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 4 and R 5 is hydrogen and R6 is a saturated monocyclic 4- to 6-membered cycloalkyl or a 4- to 10-membered bridged cycloalkyl, and the saturated monocyclic cycloalkyl or bridged cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 and the compound is optionally substituted with 1, 2, or 3 substituents independently selected from alkyl, and is not selected from: [ka]

[0371] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0372] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 4 and R 5 is hydrogen and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl or a 4- to 10-membered bridged cycloalkyl, which is unsubstituted or substituted with halogen, C 3~6 Cycloalkyl, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0373] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or has one C 3~6 It is substituted with cycloalkyl.

[0374] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or has one C substituted or unsubstituted ring selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 3~6 It is substituted with cycloalkyl.

[0375] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl, which is unsubstituted or substituted with one cyclopropyl.

[0376] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R6 is cyclohexyl substituted with one cyclopropyl.

[0377] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 teeth, [ka] It is.

[0378] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 9]

[0379] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or contains 1, 2 or 3 C 1~6 It is substituted with alkyl.

[0380] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or has three C 1~6 It is substituted with alkyl.

[0381] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or 3 -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, and tert-butyl; 1~6 It is substituted with alkyl.

[0382] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, which is unsubstituted or has 3 CH 3 - has been replaced.

[0383] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 2 or 3 CH 3 -substituted cyclobutyl, cyclopentyl, and cyclohexyl.

[0384] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 2 or 3 CH 3 -substituted cyclohexyl.

[0385] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 2 or 3 CH 3 -, and cyclohexyl substituted with one or two hydroxy groups.

[0386] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is selected from: [ka]

[0387] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, which is unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 10] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl or a saturated monocyclic 4- to 6-membered cycloalkyl, which is free of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0388] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R6 is an unsubstituted 4-10 membered bridged cycloalkyl.

[0389] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0390] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, which is unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 are Cl-, F-, and CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 It is a 4-10 membered bridged cycloalkyl substituted by three substituents independently selected from O-, cyano and hydroxy.

[0391] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is imidazolyl, which may be substituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 11] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is oxazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, the bridged cycloalkyl being selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0392] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is oxazolyl, unsubstituted or substituted as described herein; R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted 4-10 membered bridged cycloalkyl.

[0393] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is one haloC as described herein. 1~6 is an alkyl-substituted oxazolyl; R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0394] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is oxazolyl, which may be substituted or unsubstituted as described herein; n, R2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 12] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, and oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, and oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka]

[0395] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1is selected from pyrazolyl, imidazolyl, and oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl, or oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka]

[0396] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is selected from pyrazolyl, imidazolyl and oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka]

[0397] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R1 is selected from pyrazolyl, imidazolyl, and oxazolyl, which are unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 and R 5 is as described herein, and R 6 is selected from: [ka]

[0398] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is a 5-membered heteroaryl selected from pyrazolyl, imidazolyl, and oxazolyl, unsubstituted or substituted as described herein; n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, with non-limiting examples selected from: [Table 13] TIFF2024542881000156.tif104165 In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is HaroC 1~6 It is an alkyl.

[0399] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 is 5-12 membered heterocycloalkyl, 6 membered heteroaryl, 4-10 membered cycloalkyl, phenyl, C 1~6 Alkyl and haloC1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0400] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 is selected from 5-12 membered heterocycloalkyl, 6 membered heteroaryl, and 4-10 membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0401] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C 1~6 Alkyl; and e) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, a cycloalkenyl, a bridged cycloalkyl, a bicyclic edge-fused cycloalkyl, or a phenyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0402] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, cycloalkenyl, bridged cycloalkyl, or bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0403] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3-, cyclopropyl, CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0404] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 is alkyl, R 6 is selected from dihydrochromenyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl; Chromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl, or pyridinyl is not an alkyl radical, Cl-, F-, CH 3 -, CH 2 F-, CF 3 -, (CH 3 ) 2 CF-, cyclopropyl, and CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0405] R 1 HaroC 1~6 In some embodiments where alkyl is selected from the following: [ka]

[0406] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is (CH 3 ) 2 CF-, CF 3 CH 2 -, CH 3 CF 2 -, CF 3 -, CH 2 F-, or CHF 2 -Halo C selected from 1~6 It is an alkyl.

[0407] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 -, CF 3 -, CF 3 CH 2 - and C-H 3 CF 2 is selected from.

[0408] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CH 3 CF 2 -It is.

[0409] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 CH 2 -It is.

[0410] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -It is.

[0411] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is CHF 2 -It is.

[0412] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 (CH 3 ) 2 CF-, CF 3 CH 2 -, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 - selected from R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0413] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 (CH 3 ) 2 CF-, CF 3 CH 2 -, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 - selected from R 2 and R 3 is hydrogen, n is 0, 1, or 2, and R6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0414] In some embodiments, when n is 1 or 2, R 4 and R 5 is hydrogen.

[0415] In some embodiments, n is 0 or 1.

[0416] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 (CH 3 ) 2 CF-, CF 3 CH 2 -, CH 3 CF 2 -, CF 3 -, CH 2 F-, or CHF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0417] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted 4-10 membered bridged cycloalkyl.

[0418] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is selected from unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl.

[0419] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0420] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3is hydrogen, n is 0, and R 6 is selected from unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl, which are substituted with one or two halogens, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with alkyl.

[0421] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 are unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl, which contain one or two F- or CF 3 - which may be optionally substituted.

[0422] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0423] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2- and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 are unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl, which contain one or two F- or CF 3 - which may be optionally substituted.

[0424] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 alkyl, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, with non-limiting examples selected from: [Table 14] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, the saturated monocyclic cycloalkyl containing one, two, or three halogens, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with alkyl.

[0425] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, the saturated monocyclic cycloalkyl being one haloC 1~6 It may be optionally substituted with alkyl.

[0426] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl selected from cyclobutyl, cyclopentyl, and cyclohexyl, wherein the cyclobutyl, cyclopentyl, or cyclohexyl is selected from one haloC 1~6 It is substituted with alkyl.

[0427] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl selected from cyclobutyl, cyclopentyl, and cyclohexyl, wherein cyclobutyl, cyclopentyl, or cyclohexyl is (CH3 ) 2 CF-, CF 3 CH 2 -, CH 3 CF 2 -, CF 3 -, CH 2 F-, and CHF 2 -One halo selected from 1~6 It is substituted with alkyl.

[0428] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H 3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl selected from cyclobutyl, cyclopentyl, and cyclohexyl, wherein the cyclobutyl, cyclopentyl, or cyclohexyl is selected from one CF 3 - has been replaced.

[0429] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 - and R 2 and R 3 is hydrogen, n is 0, and R 6 is one CF 3 -substituted cyclobutyl.

[0430] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 -, CHF 2 -, CF 3 CH 2 - and C-H3 CF 2 - selected from R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl selected from unsubstituted cyclobutyl, cyclopentyl, and cyclohexyl.

[0431] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 alkyl, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, with non-limiting examples selected from: [Table 15] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 - and R 2 and R 3 is hydrogen, n is 0, and R 6 The structure is: [ka] is a saturated monocyclic 4-6 membered cycloalkyl having the formula:

[0432] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 CF 3 - and R 2 and R 3 is hydrogen, n is 0, and R 6 The structure is: [ka] is a saturated monocyclic 4-6 membered cycloalkyl having the formula:

[0433] In a particularly preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 alkyl, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and a non-limiting example has the structure: [Table 16]

[0434] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Halo C 1~6 alkyl, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, with non-limiting examples selected from: [Table 17] TIFF2024542881000164.tif48165

[0435] In one embodiment, the present invention provides a method for the preparation of a pharmaceutical composition comprising the steps of: 1 is cyano, or a solvate or pharma- ceutically acceptable salt thereof.

[0436] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R6 is 5-12 membered heterocycloalkyl, 6 membered heteroaryl, 4-10 membered cycloalkyl, phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0437] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 6 is selected from 5-12 membered heterocycloalkyl, 6 membered heteroaryl, and 4-10 membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0438] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from a saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C 1~6 Alkyl; and f) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, a cycloalkenyl, a bridged cycloalkyl, a bicyclic edge-fused cycloalkyl, or a phenyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 or a solvate or pharma- ceutically acceptable salt thereof.

[0439] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0440] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano; dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3 -, cyclopropyl, CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0441] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 6 is selected from dihydrochromenyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl; Chromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl, or pyridinyl is not an alkyl radical, Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3 , cyclopropyl, CH 3It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0442] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen.

[0443] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen and n is 0, 1, or 2.

[0444] In some embodiments, when n is 1 or 2, R 4 and R 5 is hydrogen.

[0445] In some embodiments, it is 0 or 1.

[0446] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen and n is 0.

[0447] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0448] In some embodiments of the compounds of Formula (I), R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 and the compound is optionally substituted with 1, 2, or 3 substituents independently selected from alkyl, and the compound is not: [ka]

[0449] In some embodiments, the compound is not excluded from any medical use, kit, or pharmaceutical composition.

[0450] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is selected from the group consisting of halogen, C 1~6 Alkyl or haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0451] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is one, two, or three C 1~6 It may be optionally substituted with alkyl.

[0452] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4- to 10-membered bridged cycloalkyl, or a saturated monocyclic 4- to 6-membered cycloalkyl, and the bridged cycloalkyl or saturated monocyclic cycloalkyl is a cycloalkyl having three C 1~6 It may be optionally substituted with alkyl.

[0453] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl, and the saturated monocyclic cycloalkyl is CH 3 -, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, and tert-butyl; 1~6 It may be optionally substituted with alkyl.

[0454] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl, the saturated monocyclic cycloalkyl being one having three C 1~6 It may be optionally substituted with alkyl.

[0455] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl selected from cyclobutyl, cyclopentyl, and cyclohexyl, where cyclobutyl, cyclopentyl, and cyclohexyl are substituted with three CH 3 - which may be optionally substituted.

[0456] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a cyclohexyl, which has three CH 3 - has been replaced.

[0457] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and non-limiting examples are as follows: [Table 18]

[0458] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl, which is substituted with halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0459] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is a 4-10 membered bridged cycloalkyl selected from bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl, which are free of halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0460] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted 4-10 membered bridged cycloalkyl.

[0461] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6is selected from unsubstituted bicyclo[1.1.1]pentanyl and bicyclo[2.2.1]heptanyl.

[0462] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is unsubstituted bicyclo[2.2.1]heptanyl.

[0463] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, and non-limiting examples are as follows: [Table 19]

[0464] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 has 3 CH 3- and R 1 is a 4- to 10-membered bridged cycloalkyl or a saturated monocyclic 4- to 6-membered cycloalkyl optionally substituted with

[0465] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6is a 4- to 10-membered bridged cycloalkyl or a saturated monocyclic 4- to 6-membered cycloalkyl, which may be optionally substituted as described herein; R 6 A non-limiting example of the structure is as follows: [ka]

[0466] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano and R 2 and R 3 is hydrogen, n is 0, and R 6 is an unsubstituted 4- to 10-membered bridged cycloalkyl, or 3 CH 3 -substituted saturated monocyclic 4-6 membered cycloalkyl; R 6 A non-limiting example of the structure is as follows: [ka]

[0467] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is cyano, n, R 2 , R 3 , R 4 , R 5 、 and R 6 is as described herein, with non-limiting examples selected from: [Table 20]

[0468] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 It is an alkoxy.

[0469] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 is 5-12 membered heterocycloalkyl, 6 membered heteroaryl, 4-10 membered cycloalkyl, phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0470] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 is selected from 5-12 membered heterocycloalkyl, 6 membered heteroaryl, and 4-10 membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0471] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C 1~6 Alkyl; and f) Halo C 1~6 alkyl, A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, a cycloalkenyl, a bridged cycloalkyl, a bicyclic edge-fused cycloalkyl, or a phenyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0472] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0473] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl or pyridinyl is selected from Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3 -, cyclopropyl, CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-, cyano, and hydroxy.

[0474] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 6 is selected from dihydrochromenyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl; Chromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl, or pyridinyl is not an alkyl radical, Cl-, F-, CH 3 -, CH 3 CH 2 -, CF 3-, cyclopropyl, CH 3 It may be optionally substituted with 1, 2, or 3 substituents independently selected from O-cyano, and hydroxy.

[0475] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen.

[0476] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen and n is 0, 1, or 2.

[0477] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen and n is 0.

[0478] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl, which is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0479] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl, which is optionally substituted with halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with a substituent selected from alkyl.

[0480] In a preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4-6 membered cycloalkyl, which is optionally substituted with halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with one substituent selected from alkyl.

[0481] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 is alkyl, R 2 and R 3 is hydrogen, n is 0, and R 6 is a saturated monocyclic 4- to 6-membered cycloalkyl selected from cyclobutyl, cyclopentyl, and cyclohexyl, wherein the cyclobutyl, cyclopentyl, or cyclohexyl is selected from halogen, C 1~6 Alkyl and haloC 1~6It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0482] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 NC-CH 2 O-, NC-CH 2 CH 2 O-, and NCCH 2 CH 2 CH 2 Cyano C selected from O 1~6 It is an alkoxy.

[0483] In a preferred embodiment, cyano C 1~6 Alkoxy is NC-CH 2 It is O-.

[0484] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 NC-CH 2 O- and R 2 and R 3 is hydrogen, n is 0, and R 6 is one halo 1~6 It is an alkyl substituted cyclobutyl.

[0485] In a more preferred embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 NC-CH 2 O- and R 2 and R 3 is hydrogen, n is 0, and R 6 is one CF 3 -substituted cyclobutyl.

[0486] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 NC-CH 2O- and R 2 and R 3 is hydrogen, n is 0, and R 6 has the following structure: [ka]

[0487] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 NC-CH 2 O- and R 2 and R 3 is hydrogen, n is 0, and R 6 has the following structure: [ka]

[0488] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 Cyano C 1~6 Alkoxy, n, R 2 , R 3 , R 4 , R 5 , and R 6 is as described herein, and a non-limiting example has the structure: [Table 21]

[0489] In one embodiment, the present invention provides a method for the preparation of a pharmaceutical composition comprising the steps of: 1 C 1~6 or a solvate or pharma- ceutically acceptable salt thereof.

[0490] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R6 is 5-12 membered heterocycloalkyl, 6 membered heteroaryl, 4-10 membered cycloalkyl, phenyl, C 1~6 Alkyl and haloC 1~6 alkyl, heterocycloalkyl, heteroaryl, cycloalkyl or phenyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0491] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 is selected from 5-12 membered heterocycloalkyl, 6 membered heteroaryl, and 4-10 membered cycloalkyl, and the heterocycloalkyl, heteroaryl, or cycloalkyl is selected from halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0492] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; and e) Halo C 1~6 alkyl, Bicyclic edge-fused heterocycloalkyl, bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, cycloalkenyl, bridged cycloalkyl, or bicyclic edge-fused cycloalkyl, or phenyl is selected from the group consisting of halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0493] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl, C 3~6 Cycloalkyl, C 1~6 Alkoxy, cyano, oxo, hydroxy, hydroxyC 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1, 2, or 3 substituents independently selected from alkyl.

[0494] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; A bicyclic edge-fused heterocycloalkyl, a bridged heterocycloalkyl, a heteroaryl, a saturated monocyclic cycloalkyl, or a bicyclic edge-fused cycloalkyl is optionally substituted with halogen, C 1~6 Alkyl and haloC 1~6 It may be optionally substituted with 1 or 2 substituents independently selected from alkyl.

[0495] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 teeth, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl containing one aliphatic ring and one aromatic ring (wherein one ring contains one O atom), 7-10 membered bicyclic edge-fused heterocycloalkyl containing two aliphatic rings (wherein one ring contains one O atom or one N atom), and 7-10 membered bridged heterocycloalkyl (wherein the bridge contains an O atom); b) 6-membered heteroaryl; c) a 4-10 membered cycloalkyl selected from saturated monocyclic 4-6 membered cycloalkyl, a 6 membered cycloalkenyl, a 4-10 membered bridged cycloalkyl, and a 7-10 membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; Bicyclic edge-fused heterocycloalkyl, bridged heterocycloalkyl, heteroaryl, saturated monocyclic cycloalkyl, or bicyclic edge-fused cycloalkyl is not limited to Cl-, F-, CH 3 - and CF 3 -, optionally substituted with 1 or 2 substituents independently selected from:

[0496] In one embodiment, the present invention provides a compound of formula (I), or a solvate or pharma- ceutically acceptable salt thereof, wherein R 1 is C 1~6 Alkoxy, R 6 are dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, tert-butyl, bicyclo[2.2.2]octanyl, (CH 3 ) 2 CF-, bicyclo[3.1.0]hexanyl, oxolanyl, octahydropentalenyl, hexahydrocyclopenta[b]furanyl, pyrazinyl, pyrimidinyl and pyridinyl, and dihydrochromenyl, cyclopentyl, phenyl, cyclohexyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]heptanyl, cyclohexenyl, cyclobutyl, bicyclo[2.2.2]octanyl, bicyc...

Claims

1. Formula (I'): 【Chemistry 1】 (In the formula, Y １ is CR ａ or N, Y ２ is CR ｂ or N, Y ３ is CR ｃ or N, However, Y １ , Y ２ and Y ３ Only 0 or 1 in the above is N, and the rest is CR ａ , C.R. ｂ , or CR ｃ and R ａ , R ｂ and R ｃ are each independently selected from hydrogen or halogen; R １ is a 4- to 6-membered heterocycloalkyl, cyano, haloC １～６ Alkoxy, HaloC １－６ Alkylthio, C １～６ Alkoxy, 4- to 6-membered heterocyclyloxy, 4- to 6-membered cycloalkyloxy, halogen, haloC １～６ Alkyl, C ３～５ Cycloalkyl C １～６ Alkoxy, Cyano C １～６ alkoxy and 5-membered heteroaryl, wherein said heterocycloalkyl, said heterocyclyloxy and said heteroaryl are selected from one C １～６ Alkyl or halo C １～６ The 4- to 6-membered cycloalkyloxy may be optionally substituted with 1, 2, or 3 substituents independently selected from halogen, and the haloC １～６ Alkoxy is C １～６ optionally substituted with alkoxy; R ２ and R ３ is hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy and Hydroxy C １～６ independently selected from alkyl, or R ２ and R ３ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ４ and R ５ are independently hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy, hydroxy C １～６ Alkyl, haloC １～６ selected from alkyl and hydroxy; R ４ and R ５ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ６ is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, C １～６ Alkyl, haloC １～６ Alkyl, haloC １～６ Alkoxy and Si(C １～６ alkyl) ３ wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl or said phenyl is selected from halogen, C １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, cyano, oxo, hydroxy, hydroxy C １～６ Alkyl, haloC １～６ Alkyl and C ２～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkynyl; n is 0, 1, 2, or 3, or a solvate or pharmaceutically acceptable salt thereof.

2. The compound has the formula (I): 【Chemistry 2】 (In the formula, R １ is a 4- to 6-membered heterocycloalkyl, cyano, haloC １～６ Alkoxy, HaloC １－６ Alkylthio, C １～６ Alkoxy, 4- to 6-membered heterocyclyloxy, 4- to 6-membered cycloalkyloxy, halogen, haloC １～６ Alkyl, C ３～５ Cycloalkyl C １～６ Alkoxy, Cyano C １～６ alkoxy and 5-membered heteroaryl, wherein said heterocycloalkyl, said heterocyclyloxy and said heteroaryl are selected from one C １～６ Alkyl or halo C １～６ The 4- to 6-membered cycloalkyloxy may be optionally substituted with 1, 2, or 3 substituents independently selected from halogen, and the haloC １～６ Alkoxy is C １～６ optionally substituted with alkoxy; R ２ and R ３ is hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy and Hydroxy C １～６ independently selected from alkyl, or R ２ and R ３ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ４ and R ５ is hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy, hydroxy C １～６ Alkyl, haloC １～６ independently selected from alkyl and hydroxy; R ４ and R ５ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ６ is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, a phenyl, C １～６ Alkyl, haloC １～６ Alkyl, haloC １～６ Alkoxy and Si(C １～６ alkyl) ３ wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl or said phenyl is selected from halogen, C １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, cyano, oxo, hydroxy, hydroxy C １～６ Alkyl, haloC １～６ Alkyl and C ２～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkynyl; and n is 0, 1, 2, or 3, or a solvate or pharmaceutically acceptable salt thereof.

3. Formula (I): 【Transformation 3】 (In the formula, R １ is a 4- to 6-membered heterocycloalkyl, cyano, haloC １～６ Alkoxy, C １～６ Alkoxy, 4- to 6-membered heterocyclyloxy, halogen, haloC １～６ Alkyl, C ３～５ Cycloalkyl C １～６ Alkoxy, Cyano C １～６ alkoxy and 5-membered heteroaryl, wherein said heterocycloalkyl, said heterocyclyloxy and said heteroaryl are selected from one C １～６ Alkyl or halo C １～６ optionally substituted with alkyl; R ２ and R ３ is hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy and Hydroxy C １～６ independently selected from alkyl, or R ２ and R ３ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ４ and R ５ is hydrogen, deuterium, C １～６ Alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, C １～６ Alkoxy, hydroxy C １～６ independently selected from alkyl and hydroxy; R ４ and R ５ together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R ６ is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 4- to 10-membered cycloalkyl, a phenyl, C １～６ Alkyl, and haloC １～６ alkyl, wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl or said phenyl is selected from halogen, C １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Alkoxy, cyano, oxo, hydroxy, hydroxy C １～６ Alkyl and HaloC １～６ optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; and n is 0, 1, 2, or 3, or a solvate or pharmaceutically acceptable salt thereof.

4. Y １ , Y ２ is CH, Y ３ is selected from CH or N; 2. A compound of formula (I') according to claim 1, or a solvate or pharmaceutically acceptable salt thereof.

5. (i) R １ But, cyano, halo C １～６ Alkoxy, HaloC １～６ Alkylthio, 4- to 6-membered heterocyclyloxy, halogen, haloC １～６ Alkyl, C ３－５ Cycloalkyl C １～６ Alkoxy and cyano C １～６ alkoxy, wherein said heterocyclyloxy and said cycloalkylalkoxy are selected from one C １～６ Alkyl or halo C １～６ optionally substituted with alkyl; or (ii) R １ is halogen or haloC １～６ a 5-membered heteroaryl selected from pyrazolyl and imidazolyl optionally substituted with 1, 2, or 3 substituents independently selected from alkyl; 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof.

6. (i) R ２ and R ３ are both hydrogen, or (ii) R ２ and R ３ One of the groups is hydrogen and the other is hydroxy C １～６ is alkyl, 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof.

7. 3. A compound of formula (I') or (I) according to claim 1 or 2, wherein n is 0 or 1, or a solvate or pharmaceutically acceptable salt thereof.

8. n is 1, and (i) R ４ and R ５ are hydrogen, or (ii) R ４ and R ５ One of them is hydrogen and the other is C １～６ Alkyl, haloC １～６ alkyl, saturated monocyclic 3- to 5-membered cycloalkyl, or C １～６ 3. The compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, which is alkoxy.

9. R ４ and R ５ and R 1 and R 2 together with the carbon atom to which they are attached form cyclopropyl, or a solvate or pharmaceutically acceptable salt thereof.

10. R ６ is a 5- to 12-membered heterocycloalkyl, a 6-membered heteroaryl, a 3- to 10-membered cycloalkyl, C １～６ Alkyl, haloC １～６ Alkyl, Si(C １～６ alkyl) ３ and phenyl, wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl or said phenyl is selected from halogen, C １～６ Alkyl, C ３～６ Cycloalkyl, C １～６ Alkoxy, HaloC １～６ Alkoxy, cyano, oxo, hydroxy, hydroxy C １～６ Alkyl and HaloC １～６ 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, optionally substituted with 1, 2 or 3 substituents independently selected from alkyl.

11. R ６ but, a) 5-12 membered heterocycloalkyl, wherein the heterocycloalkyl is selected from 7-10 membered bicyclic edge-fused heterocycloalkyl comprising one aliphatic ring and one aromatic ring, wherein one ring contains one O atom, 7-10 membered bicyclic edge-fused heterocycloalkyl comprising two aliphatic rings, wherein said one ring contains one O atom or one N atom, and 7-10 membered bridged heterocycloalkyl, wherein said bridge contains an O atom; b) 6-membered heteroaryl; c) a 3- to 10-membered cycloalkyl selected from saturated monocyclic 3- to 6-membered cycloalkyl, a 6-membered cycloalkenyl, a 4- to 10-membered bridged cycloalkyl, and a 7- to 10-membered bicyclic edge-fused cycloalkyl containing two aliphatic rings; d) phenyl; e) C １～６ Alkyl; f) Halo C １～６ Alkyl; g) Si(C １－６ alkyl) ３ and optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, cyano, oxo, hydroxy, hydroxyC 1-6 alkyl and haloC 1-6 alkyl; 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof.

12. R ６ but the following: 【Chemistry 4】 【change】 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, selected from:

13. R １ But CHF ２ O-, unsubstituted pyrazolyl, unsubstituted imidazolyl, CH ３ O-, (CH ３ )CF ２ -, CN-, CHF ２ -, CF ３ -, CF ３ CH ２ O-, CH ３ CFHCH ２ O-, CF ２ H-S-; R ２ and R ３ is hydrogen, n is 0 or 1, and (i) R ４ and R ５ is hydrogen, or (ii) R ４ and R ５ is hydrogen and the other is cyclopropyl, or (iii) R ４ and R ５ One of them is hydrogen and the other is CF ３ -, CHF ２ , and C.H. ２ F, or (iv) R ４ and R ５ together with the carbon atom to which they are attached form a cyclopropyl, and R ６ is selected from 5-12 membered heterocycloalkyl (wherein the heterocycloalkyl is a bicyclic edge-fused heterocycloalkyl comprising one aliphatic ring and one aromatic ring, each ring containing one O atom; a 7-10 membered bicyclic edge-fused heterocycloalkyl comprising two aliphatic rings, each ring containing one O atom or one N atom; a 7-10 membered bridged heterosystem, the bridge containing an O atom); a 6 membered heteroaryl; and a 3-10 membered cycloalkyl selected from cyclopropyl, saturated monocyclic 4-6 membered cycloalkyl, 4-10 membered bridged cycloalkyl, and 7-10 membered bicyclic edge-fused cycloalkyl comprising two aliphatic rings; both 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, cyano, oxo, hydroxy, hydroxyC 1-6 alkyl, and haloC 1-6 alkyl; or one, two, or three substituents independently selected from Cl—, F—, CH 3 —, CH 2 F—, CF 3 —, (CH 3 ) 2 CF—, cyclopropyl, and CH 3 O—, CF 3 O—, CHF 2 O—, cyano, and hydroxy; or 1, 2, or 3 substituents independently selected from Cl—, F—, CH 3 —, CF 3 —, cyclopropyl, CH 3 O—, CF 3 O—, and CHF 2 O—; or 1, 2 or 3 substituents independently selected from F—, CF 3 —, CF 3 O— and CHF 2 O—; 3. A compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, optionally substituted with:

14. 3. The compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, wherein the compound is selected from the following: Table 78

15. R １ is CHF ２ O- and R ６ is substituted with one or two F-, and / or with the proviso that the compound is 【Transformation 5】 and 【Transformation 6】 3. The compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, which is not selected from:

16. The compound of formula (I) inhibits Kv7.2 EC ５０ 3. A compound of formula (I) according to claim 2, or a solvate or pharmaceutically acceptable salt thereof, which exhibits <3 μM and a selectivity ratio Kv7.5 — 7.3 / Kv7.2 > 10x.

17. A pharmaceutical composition comprising a compound of formula (I') or (I) according to claim 1 or 2, or a solvate or pharmaceutically acceptable salt thereof, The pharmaceutical composition may further comprise one or more pharmaceutical excipients.

18. The pharmaceutical composition of claim 17, wherein (i) Compounds of formula (I') or a solvate or pharmaceutically acceptable salt thereof, wherein Y 1 and Y 2 are CH; Y 3 is selected from CH or N; R 1 is selected from 4- to 6-membered heterocycloalkyl, cyano, haloC 1-6 alkoxy, haloC 1-6 alkylthio, C 1-6 alkoxy, 4- to 6-membered heterocyclyloxy, halogen, haloC 1-6 alkyl, C 3-5 cycloalkylC 1-6 alkoxy, cyanoC 1-6 alkoxy and 5-membered heteroaryl, wherein said heterocycloalkyl, said heterocyclyloxy and said heteroaryl are optionally substituted with one C 1-6 alkyl or haloC 1-6 alkyl; R 2 and R 3 are independently selected from hydrogen and hydroxyC 1-6 alkyl; R 4 and R 5 are independently selected from hydrogen, saturated monocyclic 3- to 5-membered cycloalkyl, haloC 1-6 alkyl and C 1-6 alkyl; or R 4 and R 5 together with the carbon atom to which they are attached form a saturated monocyclic 3- to 5-membered cycloalkyl; R 6 is selected from 5- to 12-membered heterocycloalkyl, 6-membered heteroaryl, 3- to 10-membered cycloalkyl, Si(C 1-6 alkyl) 3 and phenyl, wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl or said phenyl is optionally substituted with 1, 2 or 3 substituents independently selected from halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, cyano, oxo, hydroxy, hydroxyC 1-6 alkyl, haloC 1-6 alkoxy and haloC 1-6 alkyl; n is 0, 1 or 2; or (ii) Compounds of formula (I') or a solvate or pharmaceutically acceptable salt thereof, wherein Y 1 and Y 2 are CH; Y 3 is selected from CH or N; R 1 is selected from 4- to 6-membered heterocycloalkyl, cyano, haloC 1-6 alkoxy, haloC 1-6 alkylthio, C 1-6 alkoxy, 4- to 6-membered heterocyclyloxy, halogen, haloC 1-6 alkyl, C 3-5 cycloalkylC 1-6 alkoxy, cyanoC 1-6 alkoxy or 5-membered heteroaryl, wherein said heterocycloalkyl, said heterocyclyloxy and said heteroaryl are optionally substituted with one C 1-6 alkyl or haloC 1-6 alkyl; R 2 and R 3 are independently selected from hydrogen and hydroxyC 1-6 alkyl; R 4 and R 5 are independently selected from hydrogen, saturated monocyclic 3- to 5-membered cycloalkyl, haloC 1-6 alkyl, and hydroxyC 1-6 alkyl; R 6 is selected from 5- to 12-membered heterocycloalkyl, 6-membered heteroaryl, 3- to 10-membered cycloalkyl, Si(C 1-6 alkyl) 3 , and phenyl, wherein said heterocycloalkyl, said heteroaryl, said cycloalkyl, or said phenyl is optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, cyano, hydroxy, haloC 1-6 alkoxy, and haloC 1-6 alkyl; n is 0, 1 or 2; or (iii) The compound of formula (I') or (I) is selected from the group consisting of: R 1 is 【Transformation 7】 and R 6 is 【Transformation 8】 and n is 2, and R 4 and R 5 are (i) all hydrogen, or (ii) both hydrogen in a first pair of R 4 and R 5 and one hydrogen and the other hydroxy in a second pair of R 4 and R 5 ; Exclude compounds that meet all of the above criteria. or (iv) The compound of formula (I') or (I) or a solvate or pharmaceutically acceptable salt thereof, wherein R 6 is selected from saturated monocyclic 3- to 6-membered cycloalkyl, 7- to 10-membered bicyclic fused cycloalkyl, 4- to 10-membered bridged cycloalkyl, saturated monocyclic 3- to 6-membered cycloalkyl group, 7- to 10-membered bicyclic fused cycloalkyl, phenyl, Si(C 1-6 alkyl) 3 and haloC 1-6 alkyl; or (v) The compound of formula (I) or a solvate or pharmaceutically acceptable salt thereof, wherein R 6 is selected from saturated monocyclic 3- to 6-membered cycloalkyl, 7- to 10-membered bicyclic fused cycloalkyl, 4- to 10-membered bridged cycloalkyl, saturated monocyclic 3- to 6-membered cycloalkyl group, and 7- to 10-membered bicyclic fused cycloalkyl. Pharmaceutical compositions.

19. 18. The pharmaceutical composition of claim 17, 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 the disorder, disease or disability is selected from behavioral disorders, mood disorders, neurodevelopmental disorders, intellectual disabilities, epilepsy, neurodegenerative diseases, pain, migraine, and tinnitus.

20. 20. The pharmaceutical composition for use according to claim 19, for systemic or local administration such as oral, nasal, parenteral (by intravenous (both bolus and infusion), intramuscular or subcutaneous injection), transdermal, vaginal, buccal, rectal or topical administration modes, intracisternal, intraperitoneal, as an oral or nasal spray, or as a liquid aerosol or dry powder for inhalation.

21. 18. A pharmaceutical composition according to claim 17 for use in therapy.

22. 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 2; and b) instructions for use, the 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; kit. (i) Urea formation is achieved by the following reaction: 【Chemistry 9】 wherein R 1 , R 2 , R 3 , n, R 4 , R 5 and R 6 are as defined herein; or (ii) the reaction step of: 【Chemistry 10】 wherein R 1 , R 2 , R 3 , n, R 4 , R 5 and R 6 are as defined herein; or (iii) Reaction of the following reaction step: 【Chemistry 11】 wherein R 1 , R 2 , R 3 , n, R 4 , R 5 and R 6 are as defined herein; 3. A process for the preparation of a compound of formula (I') or (I) or a solvate or pharmaceutically acceptable salt thereof according to claim 1 or 2.

Images