Novel heterocyclic compounds

Abstract

To provide compounds which have activity against mGluR, preferably mGluR7.SOLUTION: The present invention provides a compound of the following formula (I).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to novel heterocyclic compounds. The present invention also relates to compounds that are modulators of metabotropic glutamate receptors (mGluR), preferably modulators of metabotropic glutamate receptor subtype 7 ("mGluR7"). The present invention also relates to pharmaceutical compositions comprising such compounds, methods for preparing such compounds and compositions, and the use of such compounds and compositions for the prevention or treatment of disorders associated with glutamate deficiency or disorders involving metabotropic glutamate receptors, preferably disorders involving the mGluR7 subtype of metabotropic glutamate receptors. [Background technology]

[0002] Glutamate is a major amino acid neurotransmitter in the mammalian central nervous system (CNS), playing a key role in some physiological functions, including learning and memory, sensory perception, synaptic plasticity development, and motor control. Furthermore, glutamate is central to some neurological and psychiatric disorders in which imbalances in glutamatergic neurotransmission are observed.

[0003] Glutamate regulates synaptic neurotransmission through the activation of mGluR. Class C G protein-coupled receptors (GPCRs), to which mGluR belongs, play a regulatory role in fine-tuning synaptic effects (Schoepp et al. Neuropharmacology (1999), 38:1431). In particular, mGlu receptor subtype 7 (mGluR7) is widely distributed in the brain and exhibits the highest degree of evolutionary conservation among all mGlu receptor species (Flor et al. Neuropharmacol. (1997), 36:153). More importantly, mGluR7 has the lowest affinity for glutamate and is inactive under normal neurotransmission conditions, but becomes active only under severe pathophysiological conditions or in response to excessive glutamate release (Ferraguti and Shigemoto, Cell Tissue Res. (2006), 326:483). MGluR7 is thought to act as a tonic break, inhibiting further glutamate release by acting on the release of other neurotransmitters (e.g., GABA), thereby preventing glutamate excitotoxicity, which is involved in many pathologies of the CNS and sensory disorders.

[0004] Specifically, mGluR7 modulators, preferably antagonists, inverse agonists, and negative allosteric modulators (NAMs), have been reported to be potential therapeutic tools for neurological, psychiatric, and mood disorders, as well as pain and hearing impairments, which are thought to be associated with clinical syndromes, based on experimental studies using laboratory animals.

[0005] Isoxazolopyridinone derivatives, such as MMPIP (6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridine-4(5H)-one hydrochloride), have been reported to be mGluR7 NAMs (Nakamura et al., Bioorg. Med. Chem. Lett. (2010), 20:726; Suzuki et al., J. Pharmacol. Exp. Ther. (2007), 323:147), exhibiting partial to complete antagonism of mGluR7 in vivo and in vitro, demonstrating context-dependent pharmacology (Niswender et al., Mol. Pharmacol. (2010), 77:459; Hikichi et al., Eur. J. Pharmacol. (2010), 10, 106). Furthermore, MMPIP exhibits reverse agonist activity due to the constitutive activity of mGluR7 (Cieslik et al., Front. Mol. Neurosci., 20 September 2018, doi:10.3389 / fnmol.2018.00316).

[0006] Tetrahydrobenzoxazole derivatives, such as (+)-6-(2,4-dimethylphenyl)-2-ethyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one (ADX71743) and its racemic form, have been reported to be mGluR7 NAMs or reverse agonists exhibiting anxiolytic and antipsychotic activity (Kalinichev et al., J. Pharmacol. Exp. Ther. (2013), 344:624; Cieslik et al., Front. Mol. Neurosci., 20 September 2018, doi:10.3389 / fnmol.2018.00316).

[0007] Chromenone derivatives, such as 7-hydroxy-3-(4-indophenoxy)-4H-chromenone (XAP044), are reported to be weak mGluR7 allosteric antagonists that bind to the extracellular domain of the receptor. XAP044 has been shown to have anxiolytic, antidepressant, antistress, and antipsychotic activity (Gee et al., J. Biol. Chem. (2014), 289:10975).

[0008] Combinatorial expression of mGluR7 in brain regions using genetically modified mice and wild-type animals, as well as pharmacological manipulation of mGluR7, are revealing that mGluR7 plays a crucial role in many CNS disorders. These CNS disorders include depression, schizophrenia, anxiety, obsessive-compulsive disorder and related symptoms (see review article Pallazo et al., Curr. Neuropharmacol. (2016), 14(5): 504), and especially acute and chronic stress-related disorders (see review article Peterlik et al., Curr Neuropharmacol. (2016), 14(5): 514). Furthermore, mGluR7 is also proving to be a new therapeutic tool for treating psychostimulant (i.e., nicotine and cocaine) addiction (Li and Markou, CNS Neurol. Disord. Drug Targets (2015), 14(6):738; Li et al., Neuropharmacology (2013), 66:12). Furthermore, mGluR7 NAM MMPIP and the allosteric antagonist XAP44 have been shown to be involved in suppressing pain responses, alleviating anxiety-like and depressive-like behaviors, and improving cognitive performance in a mouse model of neuropathic pain (Pallazzo et al., Pain (2015), 156(6):1060).

[0009] Furthermore, mGluR7 has been reported to be expressed in peripheral tissues such as the colonic mucosa and stomach (Julio-Pepper et al., Pharmacol. Rev. (2011), 63:35), suggesting its potential effectiveness in treating conditions such as visceral pain, stress-related gastrointestinal dysfunction, and diarrhea or constipation in irritable bowel syndrome (IBS) and other related disorders.

[0010] Furthermore, mGluR7 has been reported to be expressed in hair cells and spiral ganglion neurons of the inner ear (Friedman et al. (2008) WO2008 / 131439), as well as in the vestibular system (Zhou et al., Int J Mol. Sci. (2013) 14(11):22857; Horii et al., Exp. Brain Res. (2001) 139(2):188), suggesting its potential effectiveness in treating conditions related to the inner ear and auditory nervous system, such as age-related hearing loss, noise-induced hearing loss, acute and chronic hearing loss, tinnitus, Meniere's disease, and vestibular disorders.

[0011] mGluR7 has been shown to be expressed at the synaptic terminals of specific cone bipolar cells in the retina (Brandstatter et al., (1996) J. Neurosci., 16(15):4749-4756), suggesting that mGluR7 modulators may be effective in the acute and chronic treatment of glaucoma and other visual impairments.

[0012] Finally, numerous genome-wide human studies have demonstrated a link between GRM7, the gene encoding mGluR7, and serious diseases. For example, age-related hearing loss (ARHL) / presbycusis has been reported by Friedman et al. (Hum. Mol. Genet. (2009), 18:785), Van Laer et al. (Eur. J. Hum. Genet. (2010), 18:685), Newman et al. (Hear. Res. (2012), 294:125), Luo et al. (Plos One (2013), 8(10):e77153), and more recently by Haider et al. (Front. Aging Neurosci. (2017), 9:346) and Matyas et al. (Pathol. Oncol. Res. (2018), doi: 10.1007 / s12253-018-0388-6). Noise-induced hearing loss has been reported by Lu et al. (BMC Med. Genet. (2018), 19(1):4). Tinnitus has been reported by Haider et al. (Front. Aging Neurosci. (2017), 9:346). Schizophrenia has been reported by Niu et al. (Neurosci. Lett. (2015), 604:109). Attention-deficit hyperactivity disorder (ADHD) has been reported by Elia et al. (Nat. Genet. (2011), 44:78). Major depressive disorder has been reported by Li et al. (Eur. Neuropsychopharmacol. (2015), doi: 10.1016 / j.euroneuro.2015.05.004).Bipolar disorder has been reported by Kandaswamy et al. (Am. J. Med. Genet. B. Neuropsychiatr. Genet. (2015), 165B(4):365). Alcohol-related dependence has been reported by Vadasz et al. (Genomics (2007), 90(6):690). Autism spectrum disorder, such as autism, has been reported by Liu et al. (Am. J. Med. Genet. B. Neuropsychiatr. Genet. (2015), 168B(4):258).

[0013] In summary, these pharmacological and genetic data strongly support the potential effectiveness of mGluR7 modulators in treating a wide range of diseases and related symptoms, including psychiatric disorders, neurological disorders, neurodevelopmental disorders, earaches, pain, visual impairments, and gastrointestinal disorders. [Overview of the project] [Problems that the invention aims to solve]

[0014] One of the objectives of the present invention is to provide a compound having activity toward mGluR, preferably mGluR7.

[0015] Another object of the present invention is to provide a pharmaceutical composition containing such a compound.

[0016] Another object of the present invention is to provide such compounds and / or pharmaceutical compositions for treating mGluR-related diseases, preferably mGluR7-related diseases. [Means for solving the problem]

[0017] The present invention relates to the compound of the following formula (I). [ka] (Here, G is N or CR 7selected from E is N or CR 8 selected from where at least one of G or E is N Y is CR 9 and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 may be the same or different and each independently is hydrogen, halogen, -CN, -CF3, -C(=O)R 10 , -C(=O)OR 10 , -C(=O)NR 10 R 11 , -OR 10 , -OC(=O)R 10 , -OC(=O)NR 10 R 11 , -SR 10 , -S(O)R 10 , -S(O)2R 10 , -S(O)2NR 10 R 11 , -NR 10 R 11 0, -NR1 10 2C(=O)R3 11 4, -NR5 10 6C(=O)OR7 11 8, -NR9 10 0S(O)2R1 11 2, and a optionally substituted radical selected from the group consisting of -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, or -(C1-C6)cyanoalkyl, 3 4Any two radicals R5 1 6and R7 2 8, R9 3 0and R1 4 2, and R3 5 4and R5 6 6may together form oxo(=O), 7 8where R9 10 0and R11 These may be the same or different, and each may be independently selected from hydrogen and a radical which may be optionally substituted with a radical selected from -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C1-C6)cyanoalkyl, -(C3-C7)cycloalkyl, or -(C1-C6)alkylene-(C3-C7)cycloalkyl. Here, R is chosen at will. 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10 and R 11 Any two radicals selected from may together form a 3-10 member non-aromatic carbocyclic or heterocyclic ring or a 5-10 member aromatic heterocyclic ring, which may be optionally substituted by n is an integer selected from 0 or 1. Ar 1 is an aryl or complex aryl which may be substituted by any other, Ar 2 (This is an aryl or complex aryl that may be substituted by any other element.) The present invention relates to the N-oxide forms thereof, pharmaceutically acceptable salts and solvates thereof, or their optical isomers, racemates, diastereoisomers, enantiomers, or tautomers.

[0018] Surprisingly, compounds of general formula (I) exhibit metabotropic glutamate receptor activity.

[0019] Preferably, in the compound of formula (I), Ar 1 teeth, [ka] (Here, m is the number of substituents A on the ring, and is an integer equal to 0, 1, 2, 3, 4, or 5.) Represents an aryl or complex aryl selected from the available options.

[0020] Preferably, in the compound of formula (I), Ar 2 teeth, [ka] (Here, p is the number of substituents B on the ring, and is an integer equal to 0, 1, 2, 3, 4, or 5.) This represents an aryl or complex aryl selected from the given set. Naturally, if Ar2 is a biring, B may reside in either ring.

[0021] A and B may be the same or different as described above, and each may independently be hydrogen, halogen, -CN, -NO2, -OH, -NH2, -CF3, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkyl-(C3-C7)cycloalkyl, -(C3-C8)cycloalkenyl, -(C1-C6)cyanoalkyl, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-aryl, -(C1-C6)alkylene-heterocyclic, aryl, heteroaryl, heterocyclic, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 ,-(C2-C6)alkenylene-OR 13 ,-(C2-C6)alkynylene-OR 13 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 -O-(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 -(C2-C6)Alkenylene-NR 13 R 14 -(C2-C6)alkynylene-NR 13 R 14 , -SR13 、-(C1-C6) alkylene-SR 13 、-O-(C2-C6) alkylene-SR 13 、-NR 13 -(C2-C6) alkylene-SR 14 、-S(=O)-R 13 、-(C1-C6) alkylene-S(=O)-R 13 、-O-(C1-C6) alkylene-S(=O)-R 13 、-NR 13 -(C1-C6) alkylene-S(=O)-R 14 、-S(=O)2-R 13 、-(C1-C6) alkylene-S(=O)2-R 13 、-O-(C1-C6) alkylene-S(=O)2-R 13 、-NR 13 -(C1-C6) alkylene-S(=O)2-R 14 、-S(=O)2NR 13 R 14 、-(C1-C6) alkylene-S(=O)2NR 13 R 14 、-O-(C1-C6) alkylene-S(=O)2NR 13 R 14 、-NR 13 -(C1-C6) alkylene-S(=O)2NR 14 R 15 、-NR 13 -S(=O)2R 14 、-(C1-C6) alkylene-NR 13 -S(=O)2R 14 、-O-(C2-C6) alkylene-NR 13 -S(=O)2R 14 、-NR 13 -(C2-C6) alkylene-NR 14 -S(=O)2R 15 、-C(=O)-NR 13 R 14 、-(C1-C6) alkylene-C(=O)-NR 13 R 14 、-O-(C1-C6) alkylene-C(=O)-NR 13 R 14 I 、-NR 13-(C1-C6)alkylene-C(=O)-NR 14 R 15 , -NR 13 C(=O)-R 14 -(C1-C6)alkylene-NR 13 C(=O)-R 14 -O-(C2-C6)alkylene-NR 13 C(=O)-R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 C(=O)-R 15 -C(=O)-R 13 -(C1-C6)alkylene-C(=O)-R 13 -O-(C1-C6)alkylene-C(=O)-R 13 , -NR 13 -(C1-C6)alkylene-C(=O)-R 14 , -C(=O)-OR 13 -(C1-C6)alkylene-C(=O)-OR 13 -O-(C1-C6)alkylene-C(=O)-OR 13 , -NR 13 -(C1-C6)alkylene-C(=O)-OR 14 -OC(=O)-R 13 -(C1-C6)alkylene-OC(=O)-R 13 -O-(C2-C6)alkylene-OC(=O)-R 13 , -NR 13 -(C2-C6)alkylene-OC(=O)-R 14 , -NR 13 -C(=O)-NR 14 R 15 -(C1-C6)alkylene-NR 13 -C(=O)-NR 14 R 15 -O-(C2-C6)alkylene-NR 13 -C(=O)-NR 14 R 15 , -NR 13 -(C2-C6)Alkylene-NR 14 -C(=O)-NR 15 R 16 , -NR 13 -C(=O)-OR14 -(C1-C6)alkylene-NR 13 -C(=O)-OR 14 -O-(C2-C6)alkylene-NR 13 -C(=O)-OR 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -C(=O)-OR 15 -OC(=O)-NR 13 R 14 -(C1-C6)alkylene-OC(=O)-NR 13 R 14 -O-(C2-C6)alkylene-OC(=O)-NR 13 R 14 , -NR 13 -(C2-C6)alkylene-OC(=O)-NR 14 R 15 -C(=O)-(C1-C6)alkylene-NR 13 R 14 -(C1-C6)alkylene-C(=O)-(C1-C6)alkylene-NR 13 R 14 -C(=O)-(C1-C6)alkylene-OR 13 -(C1-C6)alkylene-C(=O)-(C1-C6)alkylene-OR 13 , -NR 13 -C(=S)-NR 14 R 15 -(C1-C6)alkylene-NR 13 -C(=S)-NR 14 R 15 , -NR 13 -C(=NR 14 )-NR 15 R 16又は -(C1-C6)alkylene-NR 13 -C(=NR 14 )-NR 15 R 16 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0022] Here, R 13 , R 14 , R 15 and R16 Each of these is independently selected from hydrogen, optionally substituted -(C1-C6)haloalkyl, -(C1-C6)alkyl, -(C1-C6)cyanoalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl.

[0023] Here, optionally, R 13 , R 14 , R 15 or R 16 Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, cyano, nitro, hydroxyl, amino, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0024] Here, any two radicals A and any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring may optionally be a halogen, -CN, hydroxyl, amino, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0025] Preferably, in the compound of formula (I), substituent A may be the same or different, and each may independently be hydrogen, halogen, -CN, -CF3, -OH, -NH2, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocyclic, heterocyclic, aryl, heteroaryl, -OR 13,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 -O-(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -O-(C2-C6)Alkilen-SR 13 , -NR 13 -(C2-C6) Alkilen-SR 14 -S(=O)-R 13 -S(=O)2-R 13 -S(=O)2NR 13 R 14 -(C1-C6)alkylene-S(=O)2NR 13 R 14 , -NR 13 -S(=O)2R 14 -(C1-C6)alkylene-NR 13 -S(=O)2R 14 -O-(C2-C6)alkylene-NR 13 -S(=O)2R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -S(=O)2R 15 -C(=O)-NR 13 R 14 -(C1-C6)alkylene-C(=O)-NR 13 R 14 -O-(C1-C6)alkylene-C(=O)-NR 13 R 14 , -NR 13 -(C1-C6)alkylene-C(=O)-NR 14 R 15 , -NR 13 C(=O)-R14 -(C1-C6)alkylene-NR 13 C(=O)-R 14 -O-(C2-C6)alkylene-NR 13 C(=O)-R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 C(=O)-R 15 -C(=O)-R 13 , -C(=O)-OR 13 -(C1-C6)alkylene-C(=O)-OR 13 -O-(C1-C6)alkylene-C(=O)-OR 13 , -NR 13 -(C1-C6)alkylene-C(=O)-OR 14 -OC(=O)-R 13 -(C1-C6)alkylene-OC(=O)-R 13 -O-(C2-C6)alkylene-OC(=O)-R 13 , -NR 13 -(C2-C6)alkylene-OC(=O)-R 14 or -NR 13 -C(=O)-OR 14 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0026] Here, R 13 , R 14 and R 15 Each of these is independently selected from hydrogen, optionally substituted -(C1-C6)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl.

[0027] Here, optionally, R on substituent A 13 , R 14 or R 15Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, -CN, -NO2, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0028] Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0029] Preferably, in the compound of formula (I), substituent A may be the same or different, and each may independently be hydrogen, halogen, -CN, -CF3, -OH, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocyclic, heterocyclic, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 -O(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R14 , S(=O)2NR 13 R 14 or -NR 13 -S(=O)2R 14 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0030] Here, R 13 and R 14 Each of these is independently selected from hydrogen, optionally substituted, -(C1-C3)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heterocycle, and -(C1-C6)alkylene-heterocycle.

[0031] Here, optionally, radical R on substituent A 13 and R 14 These may together form a 3-6 membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0032] Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0033] Preferably, in the compound of formula (I), substituent A may be the same or different, and each may independently be hydrogen, halogen, -CN, -CF3, -OH, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocycle, heterocycle, -O-(C1-C6)alkyl, O-(C1-C3)alkyl-(C3-C7)cycloalkyl, -(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 or -NR 13 C(=O)-R 14 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0034] Here, R 13 and R 14 Each of these is independently selected from hydrogen, optionally substituted, -(C1-C3)alkyl, -(C3-C7)cycloalkyl, and -(C1-C6)alkylene-(C3-C7)cycloalkyl.

[0035] Here, optionally, radical R on substituent A 13 and R 14 These may together form a 3-6 membered carbon ring or heterocycle, where each ring can optionally be a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0036] Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C1-C6)alkyl. 、It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0037] Preferably, in the compound of formula (I), substituent A may be the same or different, and each substituent A is independently selected from the group consisting of hydrogen, methyl, ethyl, cyclopropyl, methoxy, ethoxy, hydroxy(-OH), cyclopropoxy, methoxymethyl, hydroxymethyl, 2-methoxyethoxy, 2-hydroxyethoxy, trifluoromethyl, chloro, fluoro, cyano, dimethylamino, azetidinyl, pyrrolidinyl, morpholino, morpholinomethyl, and acetamide.

[0038] Preferably, in the compound of formula (I), substituent B may be the same or different, and each may independently be hydrogen, halogen, -CN, -CF3, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocyclic, -(C1-C6)alkylene-aryl, heterocyclic, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 -O-(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -O-(C2-C6)Alkilen-SR 13 , -NR 13 -(C2-C6) Alkilen-SR 14 -S(=O)-R13 -(C1-C6)alkylene-S(=O)-R 13 -O-(C1-C6)alkylene-S(=O)-R 13 , -NR 13 -(C1-C6)alkylene-S(=O)-R 14 -S(=O)2-R 13 -(C1-C6)alkylene-S(=O)2-R 13 -O-(C1-C6)alkylene-S(=O)2-R 13 , -NR 13 -(C1-C6)alkylene-S(=O)2-R 14 -S(=O)2NR 13 R 14 -(C1-C6)alkylene-S(=O)2NR 13 R 14 -O-(C1-C6)alkylene-S(=O)2NR 13 R 14 , -NR 13 -(C1-C6)alkylene-S(=O)2NR 14 R 15 , -NR 13 -S(=O)2R 14 -(C1-C6)alkylene-NR 13 -S(=O)2R 14 -O-(C2-C6)alkylene-NR 13 -S(=O)2R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -S(=O)2R 15 -C(=O)-NR 13 R 14 -(C1-C6)alkylene-C(=O)-NR 13 R 14 -O-(C1-C6)alkylene-C(=O)-NR 13 R 14 , -NR 13 -(C1-C6)alkylene-C(=O)-NR 14 R 15 , -NR 13 C(=O)-R 14 -(C1-C6)alkylene-NR 13 C(=O)-R 14-O-(C2-C6)alkylene-NR 13 C(=O)-R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 C(=O)-R 15 -C(=O)-R 13 -(C1-C6)alkylene-C(=O)-R 13 -O-(C1-C6)alkylene-C(=O)-R 13 , -NR 13 -(C1-C6)alkylene-C(=O)-R 14 , -C(=O)-OR 13 -(C1-C6)alkylene-C(=O)-OR 13 -O-(C1-C6)alkylene-C(=O)-OR 13 , -NR 13 -(C1-C6)alkylene-C(=O)-OR 14 -OC(=O)-R 13 -(C1-C6)alkylene-OC(=O)-R 13 -O-(C2-C6)alkylene-OC(=O)-R 13 , -NR 13 -(C2-C6)alkylene-OC(=O)-R 14 -(C1-C6)alkylene-NR 13 -C(=O)-NR 14 R 15 , -NR 13 -C(=O)-OR 14 -(C1-C6)alkylene-NR 13 -C(=O)-OR 14 -O-(C2-C6)alkylene-NR 13 -C(=O)-OR 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -C(=O)-OR 15 -OC(=O)-NR 13 R 14 -(C1-C6)alkylene-OC(=O)-NR 13 R 14 -O-(C2-C6)alkylene-OC(=O)-NR 13 R 14 , -NR 13-(C2-C6)alkylene-OC(=O)-NR 14 R 15 -C(=O)-(C1-C6)alkylene-NR 13 R 14 -C(=O)-(C1-C6)alkylene-OR 13 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0039] Here, R 13 , R 14 and R 15 Each of these is independently selected from hydrogen, optionally substituted -(C1-C6)haloalkyl, -(C1-C6)alkyl, -(C1-C6)cyanoalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl.

[0040] Here, optionally, R on substituent B 13 , R 14 or R 15 Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -NO2, -OH, -NH2, or -(C1-C6)alkyl group. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0041] Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0042] Preferably, in the compound of formula (I), substituent B may be the same or different, and each may independently be hydrogen, halogen, -CF3, -CN, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-aryl, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -S(=O)-R 13 -S(=O)2-R 13 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R 14 , -C(=O)-OR 13 -OC(=O)-R 13 -C(=O)-(C1-C6)alkylene-OR 13 or -C(=O)-R 13 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0043] Here, R 13 and R 14 Each of these is independently selected from hydrogen, optionally substituted -(C1-C6)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl.

[0044] Here, optionally, R on substituent B 13 and R 14Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0045] Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0046] Preferably, in the compound of formula (I), substituent B may be the same or different, and each may independently be hydrogen, halogen, -CF3, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heterocycle, -O-(C1-C6)alkyl, -O-(C3-C7)cycloalkyl, -O-(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-OR 13 -O-(C1-C6)alkylene-aryl, -O-(C2-C6)alkylene-O-(C1-C6)alkyl, -NR 13 R 14 or -C(=O)-R 13 A radical is selected from the group that may be substituted by any of the radicals selected from the group.

[0047] Here, R 13 and R 14 Each of these is independently selected from hydrogen, optionally substituted, -(C1-C6)alkyl, -(C3-C7)cycloalkyl, and -(C1-C6)alkylene-(C3-C7)cycloalkyl.

[0048] Here, optionally, radical R on substituent B 13 and R 14 These may together form a 3-6 membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0049] Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1C6)alkyl)2.

[0050] Preferably, in the compound of formula (I), substituent B may be the same or different, and each substituent B is independently selected from the group consisting of methyl, ethyl, cyclopropyl, methoxy, ethoxy, isopropoxy, cyclopropoxy, cyclopentyloxy, benzyloxy, cyclopropylmethoxy, methoxymethyl, 1-hydroxyethyl, 2-methoxyethoxy, 3-methoxypropoxy, trifluoromethyl, chloro, fluoro, dimethylamino, pyrrolidinyl, and acetyl.

[0051] Preferably, in the compound of formula (I), m is an integer equal to 0, 1, or 2, and / or p is an integer equal to 1, 2, or 3.

[0052] Preferably, in the compound of formula (I), Ar 1 teeth, [ka] (Here, A is as defined above, m represents the number of substituents A on the ring, and is an integer equal to 0, 1, 2, 3, or 4. Represents an aryl or complex aryl selected from the available options.

[0053] Preferably, in the compound of formula (I), Ar 1 These include pyridine-2-yl, 3-chloropyridine-2-yl, 4-chloropyridine-2-yl, 5-chloropyridine-2-yl, 3-fluoropyridine-2-yl, 4-fluoropyridine-2-yl, 5-fluoropyridine-2-yl, 6-fluoropyridine-2-yl, 3-methoxypyridine-2-yl, 4-methoxypyridine-2-yl, 5-methoxypyridine-2-yl, 6-methoxypyridine-2-yl, and 3-methylpyridine-2-yl. 5-methylpyridine-2-yl, 4-methylpyridine-2-yl, 6-methylpyridine-2-yl, 5-cyclopropylpyridine-2-yl, 5-hydroxypyridine-2-yl, 5-(methoxymethyl)pyridine-2-yl, 5-(hydroxymethyl)pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrazine-2-yl, pyrimidine-2-yl, pyrimidine-5-yl, 5-chloropyrimidine-2-yl, 5-fluorine Lopyrimidine-2-yl, 5-methylpyrimidine-2-yl, 4-cyclopropylpyrimidine-2-yl, 5-cyclopropylpyrimidine-2-yl, 4,6-dimethylpyrimidine-2-yl, 5-(trifluoromethyl)pyrimidine-2-yl, 5-(morpholinomethyl)pyrimidine-2-yl, 4-methoxypyrimidine-2-yl, 5-methoxypyrimidine-2-yl, 4-methoxy-5-methylpyrimidine-2-yl, 5-(2-methyl It represents an aryl or heteroaryl selected from thyethoxy)pyrimidine-2-yl, 5-hydroxypyrimidine-2-yl, 5-(azetidine-1-yl)pyrimidine-2-yl, 5-(pyrrolidine-1-yl)pyrimidine-2-yl, 4-morpholinopyrimidine-2-yl, 5-morpholinopyrimidine-2-yl, thiazol-2-yl, thiazol-4-yl, 1-methyl-1H-imidazol-4-yl, and 5-methoxypyrazine-2-yl.

[0054] Preferably, in the compound of formula (I), Ar 2 teeth, [ka] (Here, B and p are as defined above.) Represents an aryl or complex aryl selected from the available options.

[0055] Preferably, in the compound of formula (I), Ar 2 teeth, [ka] (Here, B and p are as defined above.) Represents an aryl or complex aryl selected from the available options.

[0056] Preferably, in the compound of formula (I), Ar 2 teeth, [ka] (Here, B and p are as defined above.) Represents an aryl or complex aryl selected from the available options.

[0057] Preferably, in the compound of formula (I), Ar 2These include 2-methylphenyl, 2,4-dimethylphenyl, 2,4,6-trimethylphenyl, 3-methoxy-2-methylphenyl, 4-methoxy-2-methylphenyl, 5-methoxy-2-methylphenyl, 2-methoxy-3-methylphenyl, 3-methoxy-4-methylphenyl, 2-methoxy-4-methylphenyl, 2-methoxy-5-methylphenyl, 3-ethoxy-2-methylphenyl, 3-isopropoxy-2-methylphenyl, 3-cyclopropoxy-2-methylphenyl, 5-cyclopropoxy-2-methylphenyl, 3-(benzyloxy)-2-methylphenyl, 3-(3-methoxypropoxy)-2-methylphenyl, 3-(2-methoxyethoxy)-2-methylphenyl, 3-acetyl-2-methylphenyl, 4-acetyl-2-methylphenyl, 4-chloro-2-methylphenyl, 2-methyl-5-(pyrrolidine-1-yl)phenyl, and 3-(dimethylamino)-2 - Represents an aryl or heteroaryl selected from methylphenyl, 5-methoxy-2,4-dimethylphenyl, 3-cyclopropylphenyl, 3-(methoxymethyl)phenyl, 3-(dimethylamino)phenyl, (1-hydroxyethyl)phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-cyclopropoxyphenyl, 5-methoxy-2-(trifluoromethyl)phenyl, 3-(cyclopentyloxy)phenyl, 2,6-difluoro-3-methoxyphenyl, 2-chloro-3-methoxyphenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-chloro-5-methoxyphenyl, 1-methylindoline-4-yl, 1,5-dimethyl-1H-indazol-4-yl, 2-chloro-3-cyclopropoxyphenyl, 1-cyclopropylindoline-4-yl, and 1-cyclopropyl-1H-indol-4-yl.

[0058] Preferably, in the compound of formula (I), R 1 , R 2 , R 3 , R 4 , R 5 and R 6 These can be the same or different, and each can be independently hydrogen, halogen, and -OR. 10 , -NR10 R 11 , selected from the group consisting of -(C1-C3) alkyl groups which may be optionally substituted. Here, R 10 and R 11 This is as defined above. Here, any two radicals R 1 and R 2 , R 3 and R 4 , and R 5 and R 6 They may form an oxo together. Here, optionally, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 Any two radicals selected from may together form a 3- to 10-membered non-aromatic carbocyclic or heterocyclic ring, which may be optionally substituted.

[0059] Preferably, in the compound of formula (I), R 1 , R 2 , R 3 , R 4 , R 5 and R 6 It is hydrogen.

[0060] Preferably, in the compound of formula (I), R 7 and R 8 However, hydrogen, halogen, -CN, -OR 10 , -NR 10 R 11 Selected from the group consisting of -CF3, which may be optionally substituted with -(C1-C3)alkyl groups. Here, R 10 and R 11 R may be the same or different, and each is independently selected from hydrogen, -(C1-C3) alkyl, or -(C3-C7) cycloalkyl. Here, R 10 and R 11 The above definition applies. Here, optionally, the two radicals R 10 and R 11 Together, they may form a 3- to 10-membered non-aromatic carbon ring or heterocycle, which may be optionally substituted.

[0061] Preferably, in the compound of formula (I), R 7 and R 8 That is hydrogen.

[0062] Preferably, in the compound of formula (I), R 9 These are hydrogen, halogen, -CN, -OR 10 , -NR 10 R 11 Selected from the group consisting of -CF3, which may be optionally substituted with -(C1-C3)alkyl groups. Here, R 10 and R 11 These may be the same or different, and each is independently selected from hydrogen or -(C1-C3)alkyl. Here, optionally, the two radicals R 10 and R 11 Together, they may form a 3- to 10-membered non-aromatic carbon ring or heterocycle, which may be optionally substituted.

[0063] Preferably, in the compound of formula (I), R 9 It is hydrogen.

[0064] Preferably, in the compound of formula (I) according to the present invention, only one of G or E is N.

[0065] In a first preferred aspect of formula (I), the present invention relates to the compound of formula (II): [ka] (Here, G, E, Ar 1 Ar 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 And Y are as defined above for the compound of formula (I). The present invention also provides the N-oxide form thereof, pharmaceutically acceptable salts and solvates thereof, or optical isomers, racemates, diastereoisomers, enantiomers, or tautomers thereof.

[0066] Preferably, in the compound of formula (II): - Ar 1 teeth, [ka] Represents an aryl or complex aryl selected from (Here: - m is the number of substituents A on the ring, and is an integer equal to 0, 1, 2, 3, or 4. - A may be the same or different, and each may independently be hydrogen, halogen, -CN, -CF3, -OH, -NH2, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocycle, heterocycle, aryl, heteroaryl, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 -O-(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -O-(C2-C6)Alkilen-SR 13 , -NR 13 -(C2-C6) Alkilen-SR 14 -S(=O)-R 13 -S(=O)2-R 13-S(=O)2NR 13 R 14 -(C1-C6)alkylene-S(=O)2NR 13 R 14 , -NR 13 -S(=O)2R 14 -(C1-C6)alkylene-NR 13 -S(=O)2R 14 -O-(C2-C6)alkylene-NR 13 -S(=O)2R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -S(=O)2R 15 -C(=O)-NR 13 R 14 -(C1-C6)alkylene-C(=O)-NR 13 R 14 -O-(C1-C6)alkylene-C(=O)-NR 13 R 14 , -NR 13 -(C1-C6)alkylene-C(=O)-NR 14 R 15 , -NR 13 C(=O)-R 14 -(C1-C6)alkylene-NR 13 C(=O)-R 14 -O-(C2-C6)alkylene-NR 13 C(=O)-R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 C(=O)-R 15 -C(=O)-R 13 , -C(=O)-OR 13 -(C1-C6)alkylene-C(=O)-OR 13 -O-(C1-C6)alkylene-C(=O)-OR 13 , -NR 13 -(C1-C6)alkylene-C(=O)-OR 14 -OC(=O)-R 13 -(C1-C6)alkylene-OC(=O)-R 13 -O-(C2-C6)alkylene-OC(=O)-R 13 , -NR 13-(C2-C6)alkylene-OC(=O)-R 14 or -NR 13 -C(=O)-OR 14 A radical selected from the group which may be substituted by any of the following; - Here, R 13 , R 14 and R 15 Each is independently selected from hydrogen, optionally substituted -(C1-C6)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl. - Here, optionally, R on substituent A 13 , R 14 or R 15 Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, -CN, -NO2, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. and / or, - Ar 2 teeth, [ka] Represents an aryl or complex aryl selected from (here - p is the number of substituents B on the ring, and is an integer equal to 0, 1, 2, 3, 4, or 5. - B may be the same or different, and each independently includes hydrogen, halogen, -CN, -CF3, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocycle, -(C1-C6)alkylene-aryl, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 -O-(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -O-(C2-C6)Alkilen-SR 13 , -NR 13 -(C2-C6) Alkilen-SR 14 -S(=O)-R 13 -(C1-C6)alkylene-S(=O)-R 13 -O-(C1-C6)alkylene-S(=O)-R 13 , -NR 13 -(C1-C6)alkylene-S(=O)-R 14 -S(=O)2-R 13 -(C1-C6)alkylene-S(=O)2-R 13 -O-(C1-C6)alkylene-S(=O)2-R 13 , -NR 13 -(C1-C6)alkylene-S(=O)2-R 14 -S(=O)2NR 13 R 14-(C1-C6)alkylene-S(=O)2NR 13 R 14 -O-(C1-C6)alkylene-S(=O)2NR 13 R 14 , -NR 13 -(C1-C6)alkylene-S(=O)2NR 14 R 15 , -NR 13 -S(=O)2R 14 -(C1-C6)alkylene-NR 13 -S(=O)2R 14 -O-(C2-C6)alkylene-NR 13 -S(=O)2R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -S(=O)2R 15 -C(=O)-NR 13 R 14 -(C1-C6)alkylene-C(=O)-NR 13 R 14 -O-(C1-C6)alkylene-C(=O)-NR 13 R 14 , -NR 13 -(C1-C6)alkylene-C(=O)-NR 14 R 15 , -NR 13 C(=O)-R 14 -(C1-C6)alkylene-NR 13 C(=O)-R 14 -O-(C2-C6)alkylene-NR 13 C(=O)-R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 C(=O)-R 15 -C(=O)-R 13 -(C1-C6)alkylene-C(=O)-R 13 -O-(C1-C6)alkylene-C(=O)-R 13 , -NR 13 -(C1-C6)alkylene-C(=O)-R 14 , -C(=O)-OR 13 -(C1-C6)alkylene-C(=O)-OR 13-O-(C1-C6)alkylene-C(=O)-OR 13 , -NR 13 -(C1-C6)alkylene-C(=O)-OR 14 -OC(=O)-R 13 -(C1-C6)alkylene-OC(=O)-R 13 -O-(C2-C6)alkylene-OC(=O)-R 13 , -NR 13 -(C2-C6)alkylene-OC(=O)-R 14 -(C1-C6)alkylene-NR 13 -C(=O)-NR 14 R 15 , -NR 13 -C(=O)-OR 14 -(C1-C6)alkylene-NR 13 -C(=O)-OR 14 -O-(C2-C6)alkylene-NR 13 -C(=O)-OR 14 , -NR 13 -(C2-C6)Alkylene-NR 14 -C(=O)-OR 15 -OC(=O)-NR 13 R 14 -(C1-C6)alkylene-OC(=O)-NR 13 R 14 -O-(C2-C6)alkylene-OC(=O)-NR 13 R 14 , -NR 13 -(C2-C6)alkylene-OC(=O)-NR 14 R 15 -C(=O)-(C1-C6)alkylene-NR 13 R 14 -C(=O)-(C1-C6)alkylene-OR 13 A radical selected from the group which may be substituted by any of the following; - Here, R 13 , R 14 and R 15Each of these is independently selected from hydrogen, optionally substituted, -(C1-C6)haloalkyl, -(C1-C6)alkyl, -(C1-C6)cyanoalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl. - Here, optionally, R on substituent B 13 , R 14 or R 15 Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, -CN, -NO2, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2.

[0067] Preferably, in the compound of formula (II): - A may be the same or different, and each independently includes hydrogen, halogen, -CN, -CF3, -OH, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocycle, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13(C2-C6) Alkilen-OR 14 -O(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R 14 , S(=O)2NR 13 R 14 or -NR 13 -S(=O)2R 14 Selected from the group consisting of radicals which may be substituted by any of the group selected from, - Here, R 13 , R 14 and R 15 Each is independently selected from hydrogen, optionally substituted -(C1-C3)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heterocycle, and -(C1-C6)alkylene-heterocycle. - Here, optionally, radical R on substituent A 13 , R 14 and R 15 These may together form a 3-6 membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C1-C6)alkyl. 、It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. and / or, - B may be the same or different, and each independently may be hydrogen, halogen, -CF3, -CN, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-aryl, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -S(=O)-R 13 -S(=O)2-R 13 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R 14 , -C(=O)-OR 13 -OC(=O)-R 13 -C(=O)-(C1-C6)alkylene-OR 13 or -C(=O)-R 13 A radical selected from the group which may be substituted by any of the following, - Here, R 13 and R 14 Each is independently selected from hydrogen, optionally substituted -(C1-C6)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl. - Here, optionally, R on substituent B 13 and R 14Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 They may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2, and / or - Only one of G or E is N.

[0068] In a second preferred aspect of formula (I), the present invention relates to the compound of formula (III): [ka] (Here, G, E, Ar 1 Ar 2 , R 1 , R 2 , R 3 , R 4 and R 9 This is defined above for the compound of formula (I). The present invention also provides the N-oxide form thereof, pharmaceutically acceptable salts and solvates thereof, or optical isomers, racemates, diastereoisomers, enantiomers, or tautomers thereof.

[0069] Preferably, in the compound of formula (III), - A may be the same or different, and each independently includes hydrogen, halogen, -CN, -CF3, -OH, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-heterocycle, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 -O(C2-C6)alkylene-NR 13 R 14 , -NR 13 -(C2-C6)Alkylene-NR 14 R 15 , -NR 13 R 14 -(C1-C6)alkylene-NR 13 R 14 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R 14 , S(=O)2NR 13 R 14 or -NR 13 -S(=O)2R 14 A radical selected from the group which may be substituted by any of the following, - Here, R 13 and R 14 Each is independently selected from hydrogen, optionally substituted -(C1-C3)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heterocycle, and -(C1-C6)alkylene-heterocycle. - Here, optionally, radical R on substituent A 13 and R 14 These may together form a 3-6 membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C1-C6)alkyl. 、 They may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2, and / or - B may be the same or different, and each independently may be hydrogen, halogen, -CF3, -CN, and -(C1-C6)alkyl, -(C1-C6)haloalkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, -(C1-C6)alkylene-aryl, heterocycle, -OR 13 ,-(C1-C6)alkylene-OR 13 -O-(C2-C6)alkylene-OR 13 、 -NR 13 (C2-C6) Alkilen-OR 14 , -NR 13 R 14 , -SR 13 ,-(C1-C6)Alkilen-SR 13 -S(=O)-R 13 -S(=O)2-R 13 , -NR 13 C(=O)-R 14 -C(=O)-NR 13 R 14 , -C(=O)-OR 13 -OC(=O)-R 13 -C(=O)-(C1-C6)alkylene-OR 13 or -C(=O)-R 13 A radical selected from the group which may be substituted by any of the following; - Here, R 13 and R 14Each is independently selected from hydrogen, optionally substituted -(C1-C6)alkyl, -(C3-C7)cycloalkyl, -(C1-C6)alkylene-(C3-C7)cycloalkyl, heteroaryl, aryl, heterocyclic, -(C1-C6)alkylene-heteroaryl, -(C1-C6)alkylene-heterocyclic, and -(C1-C6)alkylene-aryl. - Here, optionally, R on substituent B 13 and R 14 Any two radicals selected from may together form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally halogen, CN, -OH, -NH2, or -(C1-C6)alkyl. 、 It may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2. - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, -OH, -NH2, or -(C1-C6)alkyl. 、 They may be further substituted with 1 to 5 radicals independently selected from -O-(C1-C6)alkyl and -N-((C1-C6)alkyl)2, and / or - Only one of G or E is N.

[0070] Preferably, in the compound of formula (III), G is nitrogen and E is CR 8 (Here, R 8 It is as defined above.

[0071] Preferably, in the compound of formula (III), G is nitrogen and E is CH.

[0072] Furthermore, the present invention relates to the form of a racemic mixture or one or both of the individual optical isomers of the compounds according to the present invention as described herein.

[0073] Examples of particularly preferred compounds in the present invention include the compounds listed below (list of preferred compounds), as well as their N-oxide forms, pharmaceutically acceptable salts and solvates thereof, or their optical isomers, racemates, diastereoisomers, enantiomers, or tautomers. 6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, 6-(3-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, (-)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, 6-(2,4-dimethylphenyl)-2-(5-chloropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(4-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(3-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(6-fluoropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(6-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(6-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)picolinonitrile, 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile, 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)isonicotinonitrile, 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile, 6-(2,4-dimethylphenyl)-2-(5-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(methoxymethyl)pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridine-3-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrimidine-5-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(thiazol-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(thiazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(1-methyl-1H-imidazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4,6-dimethylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(4-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-hydroxypyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-(hydroxymethyl)pyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-methoxypyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-hydroxypyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(4-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridine-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-fluoropyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(trifluoromethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxy-5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(morpholinomethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(dimethylamino)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(pyridine-2-yl)-6-(o-tolyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(1-hydroxyethyl)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-3-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(1-methylindoline-4-yl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-4-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-3-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-Methoxy-2-(trifluoromethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-fluoro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-5-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(1-methylindoline-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-fluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,5-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,3-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(methoxymethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(cyclopentyloxy)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(1,5-dimethyl-1H-indazol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-Mesityl-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,6-difluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(1-cyclopropylindoline-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(dimethylamino)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-chloro-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(3-methoxypropoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-ethoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(cyclopropylmethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-isopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(2-methoxyethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(benzyloxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-(pyrrolidine-1-yl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-(azetidine-1-yl)pyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, 6-(3-methoxy-2-methylphenyl)-2-(5-(2-methoxyethoxy)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (2-(5-(2-hydroxyethoxy)-pyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridin-2-yl)-2,5,6,7-tetrahydro-1H-cyclopenta[d]-pyridazine-1-one, 7-(2,4-dimethylphenyl)-3-(pyridine-2-yl)-5,6,7,8-tetrahydroquinazoline-4(3H)-one, 6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one 2-(5-bromopyrimidine-2-yl)-6-(3-cyclopropoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, N-(2-(6-(3-cyclopropoxy-2-methylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (+)-N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (+)-6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, and 2-(5-bromo-4-methoxypyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one.

[0074] Furthermore, the present invention relates to the following compounds of formulas (IV), (V), (VI), (VII), (VIII), and (IX) as intermediates for the compounds of formulas (I), (II), and (III). [ka] Here, G, E, Ar 1 Ar 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 And Y are defined above for compounds of formulas (I), (II), and (III).

[0075] The disclosed compounds also include all pharmaceutically acceptable isotopic variations in which at least one atom is replaced by an atom having the same atomic number but a different atomic mass than that commonly found in nature. Examples of isotopes suitable for inclusion in the disclosed compounds, but are not limited to, hydrogen isotopes, for example. 2 H and 3 H; an isotope of carbon, for example 11 C, 13 C and 14 C; an isotope of nitrogen, for example 15 N; an isotope of oxygen, for example 17 O and 18 O; phosphorus isotopes, for example 32 P and 33 P; sulfur isotopes, for example 35S; an isotope of fluorine, for example 18 F; and isotopes of chlorine, for example 36 Examples include Cl, etc. Isotope changes (e.g., deuterium, 2 The use of H, etc., can improve metabolic stability and may yield certain therapeutic benefits. Furthermore, certain isotopic changes of the compounds disclosed herein may be useful for studying the drug and / or substrate tissue distribution of radioactive isotopes (e.g., tritium, 3 H, or 14 It may include C, etc. 11 C, 18 F, 15 O and 13 Substitution with positron-emitting isotopes such as 16N is useful in positron emission topography (PET) studies to analyze substrate receptor occupancy. The isotope-labeled compounds of formulas (I) to (III) can generally be used as radiolabeled tracers for image analysis. Such isotope-labeled compounds can be prepared by conventional techniques known to those skilled in the art, or by using a suitable isotope-labeled reagent instead of the conventionally used unlabeled reagent, in a manner similar to that described in the examples below.

[0076] Regarding the tautomers, the names of the tautomers with the illustrated structures are indicated. However, naturally, other tautomers not shown are also included within the scope of this invention. [Modes for carrying out the invention]

[0077] Definition of Terms The following are definitions of various terms used to describe the present invention in this specification and the appended claims.

[0078] It should be noted, as is obvious, that the definitions given to each substituent of the compound of formula (I) in this invention also apply to the corresponding substituents of the compounds of formulas (II) to (III).

[0079] Furthermore, and this is also obvious, it is possible to directly and unambiguously link the definitions of each substituent to the definitions of other substituents.

[0080] To avoid misunderstanding, it should be noted that, naturally, in this specification, "(C1-C6)" means a carbon radical having 1, 2, 3, 4, 5, or 6 carbon atoms, and "(C0-C6)" means a carbon radical having 0, 1, 2, 3, 4, 5, or 6 carbon atoms.

[0081] In this specification, "C" means carbon atom, "N" means nitrogen atom, "O" means oxygen atom, and "S" means sulfur atom.

[0082] If the subscript is an integer 0 (zero), it indicates that the radical referred to by the subscript does not exist, meaning there is a direct bond between the radicals on either side.

[0083] If the subscript is an integer 0 (zero) and the radical it refers to is an alkyl group, it indicates that the radical is a hydrogen atom.

[0084] In this specification, unless otherwise specified, the term "bond" refers to a saturated covalent bond. When two or more bonds are adjacent to each other, they are considered equivalent to a single bond. For example, in the radical -VW-, if both V and W are bonds, the radical exhibits a single bond.

[0085] In this specification, unless otherwise specified, the term “alkyl” includes both linear and branched alkyl radicals, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, t-pentyl, neopentyl, n-hexyl, i-hexyl, or t-hexyl. The term “(C0-C3)alkyl” refers to alkyl radicals having 0, 1, 2, or 3 carbon atoms, such as methyl, ethyl, n-propyl, and i-propyl.

[0086] In this specification, unless otherwise specified, the term "alkylene" includes both straight-chain and branched-chain bifunctional saturated hydrocarbon radicals. Examples include methylene, ethylene, n-propylene, i-propylene, n-butylene, i-butylene, s-butylene, t-butylene, n-pentylene, i-pentylene, t-pentylene, neopentylene, n-hexylene, i-hexylene, or t-hexylene.

[0087] In this specification, unless otherwise specified, the term "cycloalkyl" refers to a carbon ring that does not contain heteroatoms and contains monocyclic, dicyclic, or acidic cyclic unsaturated carbon rings, which may be optionally substituted. Cycloalkyls include condensed ring systems and spirocondensed ring systems. Examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthalene, adamantane, indanyl, fluorenyl, and 1,2,3,4-tetrahydronaphthalene. The term "(C3-C7) cycloalkyl" may also refer to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

[0088] In this specification, unless otherwise specified, the term "cycloalkenyl" refers to a carbon ring that does not contain heteroatoms and contains monocyclic, dicyclic, or acidic cyclic unsaturated carbon rings, which may be optionally substituted. The term "(C2-C6)cycloalkenyl" refers to a cycloalkyl radical having 2 to 6 carbon atoms and 1 or 2 double bonds. Examples, but not limited to, include cyclopentenyl and cyclohexenyl.

[0089] In this specification, unless otherwise specified, the term "alkenyl" includes both linear and branched alkenyl radicals. The term "(C2-C6) alkenyl" refers to an alkenyl radical having 2 to 6 carbon atoms and 1 or 2 double bonds. Examples, but not limited to, include vinyl, allyl, propenyl, i-propenyl, butenyl, i-butenyl, clotyl, pentenyl, i-pentenyl, and hexenyl.

[0090] In this specification, unless otherwise specified, the term "alkenylene" includes both straight-chain and branched-chain disubstituted alkenyl radicals. The term "(C2-C6)alkenylene" refers to an alkenylene radical having 2 to 6 carbon atoms and 1 or 2 double bonds. Examples, but not limited to, include vinylene, allylene, propenylene, i-propenylene, butenylene, i-butenylene, chloroethylene, pentenylene, i-pentenylene, and hexenylene.

[0091] In this specification, unless otherwise specified, the term "alkynyl" includes both linear and branched alkynyl radicals. The term (C2-C6)alkynyl refers to a radical having 2 to 6 carbon atoms and 1 or 2 triple bonds. Examples, but not limited to, include ethynyl, propargyl, butynyl, pentynyl, and hexynyl.

[0092] In this specification, unless otherwise specified, the term "alkynylene" includes both straight-chain and branched-chain disubstituted alkynylene radicals. The term (C2-C6)alkynylene has 2 to 6 carbon atoms and 1 or 2 triple bonds. Examples, but not limited to, include ethynylene, propargylene, butynylene, pentynylene, i-pentynylene, and hexynylene.

[0093] The term "aryl" refers to a monocyclic or bicyclic hydrocarbon ring system containing at least one unsaturated 6- to 10-membered aromatic ring, which may be optionally substituted. Examples of the term "aryl" and appropriate values ​​include, but are not limited to, phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indyl, and indenyl.

[0094] In this specification, unless otherwise specified, the term “heteroaryl” refers to a 5- to 10-membered monocyclic or bicyclic unsaturated aromatic ring system containing at least one heteroatom independently selected from N, O, or S, which may be optionally substituted. A heteroaryl preferably contains 1-3 heteroatoms, preferably selected from N, O, or S. Examples of “heteroaryl” include, but are not limited to, thynyl, pyridinyl, thiazolyl, isothiazolyl, furyl, pyrrolyl, triazolyl, imidazolyl, triazinyl, oxadiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolonyl, oxazolonyl, thiazolonyl, tetrazolyl, thiadiazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, tetrahydrotriazolopyridinyl, and tetrahydrotriazolopyridinyl. Examples include benzofuryl, benzothiophenyl, thionaphthyl, indolyl, isoindolyl, pyrizonil, pyridadinil, pyrazinil, pyrimidinil, quinolyl, phthalazinil, naphthilidinil, quinoxalinil, quinazolyl, imidazopyridinil, oxazolopyridinil, thiazolopyridinil, imidazopyridadinil, oxazolopyridadinil, thiazolopyridadinil, cinolyl, pteridinil, flazanil, benzotriazolyl, pyrazolopyridinil, and prinyl.

[0095] In this specification, unless otherwise specified, the terms "alkylene-aryl," "alkylene-heteroaryl," and "alkylene-cycloalkyl" refer to aryl, heteroaryl, or cycloalkyl radicals, respectively, to which substituents are attached via alkyl radicals. The term "(C1-C6)alkylene-aryl" refers to aryl-(C1-C6)-alkyl radicals, including, for example, benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-naphthylmethyl, and 2-naphthylmethyl. The term "(C1-C6)alkylene-heteroaryl" includes heteroaryl-(C1-C6)-alkyl radicals. Here, examples of complex aryls are the same as those exemplified in the definition above, and include, for example, 2-furylmethyl, 3-furylmethyl, 2-thienylmethyl, 3-thienylmethyl, 1-imidazolylmethyl, 2-imidazolylmethyl, 3-imidazolylmethyl, 2-oxazolylmethyl, 3-oxazolylmethyl, 2-thiazolylmethyl, 3-thiazolylmethyl, 2-pyridinylmethyl, 3-pyridinylmethyl, 4-pyridinylmethyl, 1-quinolylmethyl, etc. The term "-(C1-C6)alkylene-(C3-C7)cycloalkyl" includes -(C3-C7)-cycloalkyl-(C1-C6)-alkyl radicals. Here, examples of cycloalkyls are the same as those exemplified in the definition above, and include, for example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclopropylethyl, etc.

[0096] In this specification, unless otherwise specified, the term "carbocyclic ring" may be optionally substituted and refers to saturated or partially saturated monocyclic, bicyclic, or tricyclic saturated or fused ring systems of 5 to 10 members that do not contain heteroatoms. Such fused ring systems may include one partially or completely unsaturated ring (e.g., benzene) (e.g., a benzo-fused carbocyclic ring).

[0097] In this specification, unless otherwise specified, the term “heterocycle” refers to a 5- to 10-membered monocyclic or bicyclic saturated or partially saturated ring system containing at least one heteroatom independently selected from N, O, and S, which may be optionally substituted. Such a heterocycle preferably contains 1 to 3 heteroatoms selected from N, O, or S.

[0098] In this specification, unless otherwise specified, five-membered or six-membered rings containing one or more atoms independently selected from C, N, O, and S include saturated or unsaturated carbocyclic and heterocyclic rings, in addition to aromatic rings and heteroaromatic rings. Examples of such rings, though not limited to these, include furyl, isoxazolyl, isothiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridadinyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, thienyl, imidazolyl, imidazolidinyl, imidazolinyl, triazolyl, morpholinyl, piperazinyl, piperidyl, piperizonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, tetrahydrothiopyranyl, oxazolidinonyl, thiomorpholinyl, oxadiazolyl, thiadiazolyl, tetrazolyl, phenyl, cyclohexyl, cyclopentyl, cyclohexenyl, and cyclopentenyl.

[0099] In this specification, unless otherwise specified, 3- to 10-membered rings containing one or more atoms independently selected from C, N, O, and S include saturated or unsaturated carbocyclic and heterocyclic rings, in addition to aromatic rings and heteroaromatic rings. Examples of such rings, but not limited to, include imidazolidinyl, imidazolinyl, morpholinyl, piperazinyl, piperidyl, piperizonyl, pyrazolidinyl, pyrazolidinyl, pyrrolinyl, tetrahydropyranyl, thiomorpholinyl, tetrahydrothiopyranyl, furyl, pyrrolyl, dihydropyrrolyl, isoxazolyl, isothiazolyl, isoindolinonyl, dihydropyrrolo[1,2-b]pyrazolyl, oxazolyl, oxazolidinonyl, pyrazinyl, pyrazoli Examples include pyridadinyl, pyridinyl, tetrahydropyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, thienyl, imidazolyl, triazolyl, phenyl, cyclopropyl, aziridinyl, cyclobutyl, azetidinyl, oxadiazolyl, thiadiazolyl, tetrazolyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, and cyclooctenyl.

[0100] In this specification, unless otherwise specified, the terms "halo" or "halogen" refer to, for example, fluorine, chlorine, bromine, or iodine.

[0101] In this specification, unless otherwise specified, the term "haloalkyl" means a group in which an alkyl radical as defined above is substituted with one or more halo radicals. The term "(C1-C6)haloalkyl" includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, and others.

[0102] In this specification, unless otherwise specified, the term "cyanoalkyl" means a group in which an alkyl radical as defined above is substituted with one or more cyano(CN) radicals.

[0103] In this specification, unless otherwise specified, the phrase "may be optionally substituted" means that the radical has one or more further substituents. Substituents include, for example, (C1-C6)alkyl, hydroxy(-OH), (C1-C6)alkylene-OR (where R is H or (C1-C6)alkyl), mercapto(-SH), aryl, heteroaryl, heterocyclic, (C1-C6)alkylene-aryl, (C1-C6)alkylene-heterocyclic, (C1-C6)alkylene-(C3-C7)cycloalkyl, (C1-C6)alkylene-heteroaryl, halogen, trifluoroalkyl (preferably trifluoromethyl), and trifluoroalkoxy. Examples include cyano(CN), cyanoalkyl(NO2), cyanomethyl, nitro(NO2), amino(NH2), carboxyl(CO2H), carboxamide(CONH2), carbamate(NH-C(=O)OR (where R is (C1-C6)alkyl)), sulfonamide(S(=O)2-NH2), ester(C(O)OR) of formula C(O)OR (where R is (C1-C6)alkyl), and sulfonyl(S(=O)-R) (where R is (C1-C6)alkyl).

[0104] As used herein, the term "pharmaceutically acceptable" means a compound, material, excipient, composition, or dosage form suitable for contact with human and animal tissues, within the bounds of sound medical judgment, without causing excessive toxicity, irritation, allergic reactions, or other problematic complications in light of a reasonable benefit-risk ratio.

[0105] As used herein, “pharmaceutically acceptable salt” refers to a derivative of the disclosed compound obtained by modifying the parent compound to its acid salt or base salt. pharmaceutically acceptable salts include, for example, conventional non-toxic salts or quaternary ammonium salts of the parent compound formed from non-toxic inorganic or organic acids. Such conventional non-toxic salts include, for example, salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, and nitric acid, such as their mono, di, or tri salts, and salts prepared from organic acids such as, for example, acetic acid, propionic acid, succinic acid, tartaric acid, citric acid, methanesulfonic acid, benzenesulfonic acid, glucoronic acid, glutamic acid, benzoic acid, salicylic acid, toluenesulfonic acid, oxalic acid, fumaric acid, maleic acid, and lactic acid. Further addition salts include ammonium salts such as tromethamine, meglumine, and epolamine, and metal salts such as sodium, potassium, calcium, zinc, and magnesium.

[0106] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing basic or acidic moieties by conventional chemical methods. These salts can generally be prepared by reacting the free acidic or basic forms of these compounds with stoichiometric amounts of suitable bases or acids in water, organic solvents, or mixed solutions thereof. Generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, and acetonitrile are preferred. A list of suitable salts can be found in Remington's Pharmaceutical Sciences, 20 th This is described in ed., Mack Publishing Company, Easton, PA, 2000. The disclosures in this document are incorporated herein by reference.

[0107] As used herein, “pharmaceutically acceptable solvate” refers to a derivative of the disclosed compound obtained by modifying the parent compound to its solvate. Unless otherwise specified herein, “solvate” refers to a variable stoichiometric complex formed from a solute (e.g., the compound of formula (I)) and a solvent. The present invention encompasses any solvated form of the compound of formula (I) in solid form. This includes, for example, solvates with water (e.g., hydrates), or solvates with organic solvents such as methanol, ethanol, or acetonitrile (commonly known as methanelate, ethanolate, or acetonitrile, respectively), or any polymorphs thereof. Such solvents may not interfere with the biological activity of the solute.

[0108] Compounds usable in the present invention, particularly pharmaceutically acceptable prodrugs of the compound of formula (I), are derivatives having chemically or metabolically cleavable groups that are converted to the in vivo pharmaceutically active compound used in the present invention under solvolysis or physiological conditions. Prodrugs of compounds usable in the present invention can be formed by conventional methods using functional groups of the compound, such as amino, hydroxy, or carboxyl groups. Prodrug derivative forms often offer advantages in terms of solubility, tissue compatibility, or delayed release in mammals, including humans (see Bundgaard, H., Design of Prodrugs, pp. 7-9, 21-24, Elsevier, Amsterdam 1985). Prodrugs include acid derivatives well known to those skilled in the art, such as esters prepared by the reaction of a hydrophilic compound with a suitable alcohol, and amides prepared by the reaction of a hydrophilic compound with a suitable amine. When the compound used in the present invention, particularly the compound of formula (I), has a carboxyl group, examples of prodrugs include ester derivatives prepared by reacting such carboxyl group with a suitable alcohol, and amide derivatives prepared by reacting such carboxyl group with a suitable amine. Particularly preferred ester derivatives as prodrugs include methyl esters, ethyl esters, n-propyl esters, i-propyl esters, n-butyl esters, or i-butyl esters. When the compound used in the present invention has a hydroxyl group, examples of prodrugs include acyloxy derivatives obtained by reacting such hydroxyl group with a suitable acyl halide or suitable acid anhydride. When the compound used in the present invention has an amino group, examples of prodrugs include amide derivatives obtained by reacting such amino group with a suitable acid halide or suitable mixed anhydride.

[0109] The compound of formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, may be administered as a compound itself or formulated as a pharmaceutical. Within the scope of the present invention are pharmaceutical compositions comprising the compound of formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, as an active ingredient. Such pharmaceutical compositions may optionally contain one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricants, binders, colorants, pigments, stabilizers, preservatives, or antioxidants.

[0110] Such a pharmaceutical composition may contain one or more dissolution accelerators. Examples include poly(ethylene glycol), for example, poly(ethylene glycol) having a molecular weight in the range of about 200 to about 5,000 Da, ethylene glycol, propylene glycol, nonionic surfactants, tyroxapole, polysorbate 80, macrogol-15-hydroxystearate, phospholipids, lecithin, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, cyclodextrin, hydroxyethyl-3-cyclodextrin, hydroxypropyl-3-cyclodextrin, hydroxyethyl-γ-cyclodextrin, hydroxypropyl-Y-cyclodextrin, dihydroxypropyl-3-cyclodextrin, Examples include glucosyl-α-cyclodextrin, glucosyl-3-cyclodextrin, diglucosyl-3-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-3-cyclodextrin, maltosyl-Y-cyclodextrin, maltotriosyl-3-cyclodextrin, maltotriosyl-γ-cyclodextrin, dimaltosyl-3-cyclodextrin, methyl-3-cyclodextrin, carboxyalkyl thioether, hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, vinyl acetate copolymer, vinylpyrrolidone, sodium lauryl sulfate, sodium dioctyl sulfosuccinate, or any combination thereof.

[0111] In this specification, unless otherwise specified, certain compounds may exist in one or more specific geometric, optical, enantiomerous, diastereoisomerous, epimeric, stereoisomerous, tautomeristic, conformational, or anomeric forms. Examples, but not limited to, include cis and trans forms; E and Z forms; endo and exo forms, R- forms, S- forms, and meso forms; D and L forms; d and l forms; (+) and (-) forms; keto forms, enol forms, enolate forms; α and β forms; axial and equatorial forms; and combinations thereof. These are collectively referred to as "isomers" or "isomers."

[0112] It should be noted that the term "isomer" specifically includes compounds having one or more isotopic substitutions. For example, hydrogen may be any isotope. Examples, however, are not limited to these. 1 H, 2 H(D), 3 Examples include H(T), etc. C can also be any isotope. Examples are not limited to these, but... 11 C, 12 C, 13 C, 14 Examples include C, etc. O can also be any isotope. Examples are not limited to these, but... 16 O, 18 Examples include O, etc. F can be any isotope of O. Examples are not limited to these, but... 19 F, 18 Examples include F, etc.

[0113] The present invention also relates to a composition comprising at least one compound according to the present invention, preferably a pharmaceutical composition. Such a composition preferably contains the compound according to the present invention in a therapeutically effective amount. "Therapeutally effective amount" means an amount of the compound / agent according to the present invention that is effective in preventing or treating a pathological condition.

[0114] The effective therapeutic dose can be easily determined by the attending physician, as a person skilled in the art, by using the prior art or by referring to results obtained under similar circumstances. When determining the effective therapeutic dose, the attending physician considers various factors. Examples of such factors, but not limited to, include the species, size, age, and overall health status of the subject; the specific disease associated with the subject; the degree or severity of the involvement of such disease; the response of individual subjects; the specific compound administered; the method of administration; the bioavailability specific to the formulation administered; the chosen dosing regimen; the presence or absence of concomitant medications; and other relevant circumstances.

[0115] The composition may further contain pharmaceutically acceptable excipients. Such carriers or diluents must be “acceptable” in the sense that they are compatible with the other components of the composition and are not harmful to the recipient.

[0116] "Medically" or "medically acceptable" means molecular entities and compositions that, when appropriately administered to animals or humans, do not cause adverse reactions, allergic reactions, or other unexpected reactions.

[0117] As used herein, “pharmaceutically acceptable excipients” include any carrier, diluent, adjuvant, or vehicle, such as preservatives or antioxidants, fillers, disintegrants, wetting agents, emulsifiers, suspending agents, solvents, dispersion media, coatings, antimicrobial and antifungal agents, isotonic agents, absorption retarders, etc. Such media and agents used with pharmaceutically active substances are well known in the art. Conventional media or agents are considered usable in therapeutic compositions unless they are incompatible with the active ingredient. Auxiliary active ingredients may also be incorporated into the composition as appropriate therapeutic combinations.

[0118] This composition can be in various pharmaceutical forms for the purpose of administration. Suitable compositions include any composition commonly used for systemic or topical administration of drugs.

[0119] The pharmaceutical compositions of the present invention can be prepared by any method well known in the pharmaceutical industry. For example, see Gennaro et al., Remington's Pharmaceutical Sciences (18th ed., Mack Publishing Company, 1990; see especially Part 8: Pharmaceutical Preparations and their Manufacture). To prepare the pharmaceutical compositions of the present invention, a therapeutically effective amount of a specific compound is mixed tightly with a pharmaceutically acceptable carrier or diluent, optionally in the form of a salt, as the active ingredient. Such carriers or diluents can be in various forms depending on the diverse formulation suitable for the desired dosage. These pharmaceutical compositions are preferably in a unit dosage form, particularly suitable for oral, topical, rectal, or transdermal administration, parenteral injection, middle or inner ear administration, or inhalation.

[0120] Considering the ease of administration and uniformity of dosage, it is particularly advantageous to formulate the aforementioned pharmaceutical compositions as unit dosage forms. As used herein, unit dosage forms mean physically distinct units suitable for single administration, each containing a predetermined amount of the active ingredient, calculated to produce the desired therapeutic effect, in association with the necessary pharmaceutical carrier. Examples of such unit dosage forms include tablets (including scored or coated tablets), capsules, pills, powder packets, wafers, suppositories, injections, or suspensions, as well as teaspoonfuls, tablespoonfuls, and their segregated multiples.

[0121] Since the compound according to the present invention is an orally administrative compound, an orally administered pharmaceutical composition containing such a compound is particularly advantageous.

[0122] To enhance the solubility and / or stability of the compound according to the present invention in a pharmaceutical composition, it is advantageous to use α-, β-, or γ-cyclodextrins, or their derivatives, particularly hydroxyalkyl-substituted cyclodextrins, such as 2-hydroxypropyl cyclodextrin or sulfobutyl cyclodextrin. Furthermore, cosolvents such as alcohols can also improve the solubility and / or stability of the compound according to the present invention in a pharmaceutical composition.

[0123] Furthermore, the present invention relates to a method for preparing a pharmaceutical composition according to the present invention, characterized by tightly mixing a therapeutically effective amount of the compound according to the present invention with a pharmaceutically acceptable carrier.

[0124] Furthermore, the present invention relates to the use of such compounds as pharmaceutical agents.

[0125] Furthermore, the present invention relates to the use of the compound or composition according to the present invention in the preparation of pharmaceuticals or drugs.

[0126] To our surprise, the inventors discovered that the above-mentioned compound is a modulator of the mGlu receptor, preferably a modulator of mGluR7, and preferably an antagonist of mGluR7.

[0127] Accordingly, the present invention relates to compounds or compositions according to the present invention for use in modulating, preferably reducing, inhibiting, or negatively modulating, the activity of mGlu receptors, particularly the activity of mGluR7.

[0128] Furthermore, the present invention relates to the use of compounds or compositions according to the present invention in the preparation of pharmaceuticals for the purpose of regulating, preferably reducing, inhibiting, or negatively regulating, the activity of mGlu receptors, particularly mGluR7 activity.

[0129] Furthermore, the present invention relates to a method for regulating, preferably reducing, inhibiting, or negatively regulating, the activity of the mGlu receptor, particularly the activity of mGluR7, comprising administering a therapeutically effective amount of a compound or composition according to the present invention to a patient in need thereof.

[0130] According to the present invention, the terms "patient" or "patient in need" refer to an animal or human suffering from a pathological condition caused by an etiology involving active cysteine ​​protease, or an animal or human likely to suffer from such a condition. Humans are preferred as patients.

[0131] Identifying subjects requiring treatment for the diseases and conditions described herein is well within the capabilities and knowledge of those skilled in the art. Veterinarians or physicians skilled in the art can easily identify subjects requiring such treatment by using clinical examinations, physical examinations, medical / family history, or biological and diagnostic tests.

[0132] Furthermore, the present invention relates to compounds or compositions according to the present invention for use in the treatment of diseases related to glutamate deficiency.

[0133] Furthermore, the present invention relates to the use of compounds or compositions according to the present invention in the preparation of pharmaceuticals for treating diseases related to glutamate deficiency.

[0134] In particular, the present invention relates to compounds or compositions according to the present invention for use in the prevention or treatment of disorders associated with glutamate deficiency in mammals, including humans.

[0135] Furthermore, the present invention relates to a method for treating a disease associated with glutamate deficiency, comprising administering a therapeutically effective amount of a compound or composition according to the present invention to a patient in need of such treatment.

[0136] As used herein, the term “treatment” is intended to refer to all processes that may result in delaying, interrupting, preventing, or stopping the progression of a disease; however, it does not necessarily mean that all symptoms will be completely eliminated.

[0137] Furthermore, the present invention relates to anxiety disorders, such as agoraphobia, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder, and post-traumatic stress disorder. Disorders (PTSD), social phobias, other phobias; mood disorders, e.g., bipolar disorder (I & II), cyclothymic disorder, depression, dysthymic disorder, major depressive disorder, drug-induced mood disorders, mood disorders due to systemic conditions, mania, manic-depressive illness, seasonal affective disorder; muscle spasms and muscle spasm-related disorders, e.g., tremors, epilepsy, convulsions, migraines; disorders selected from the group consisting of mild cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis; disorders selected from the group consisting of psychiatric disorders, e.g., schizophrenia, delusional disorder, schizoaffective disorder, schizotypal disorder, drug-induced mental disorders; personality disorders, e.g., obsessive-compulsive personality disorder, schizoid personality disorder, schizotypal personality disorder. Id-type disorders, borderline personality disorder, anxiety-avoidant personality disorder; childhood disorders, e.g., attention deficit hyperactivity disorder, intellectual disability, Down syndrome, tic disorder, autism spectrum disorder (e.g., Rett syndrome or fragile X syndrome) and autism; hearing impairments, e.g., inner ear disorders, impairments, functional impairments or conditions, e.g., sensorineural hearing loss, age-related hearing loss (presbycusis), Meniere's disease, sudden hearing loss, noise-induced hearing loss, drug-induced hearing loss, latent hearing loss, cisplatin-induced hearing loss, aminoglycoside-induced hearing loss, otitis media, toxic hearing loss, autoimmune inner ear disorders, acute tinnitus, chronic tinnitus, central auditory processing disorder, and vestibular disorders; gastrointestinal disorders, e.g., diarrhea, constipation, gastroesophageal reflux disease. (Gastroesophageal reflux disease: GERD), lower esophageal sphincter disease or disorder, gastrointestinal motility disorders, colitis, Crohn's disease, or irritable bowel syndrome (IBS); pain disorders, such as acute pain, chronic pain, severe pain, intractable pain, inflammatory pain, postoperative pain, headache, cancer pain, neuropathic pain, post-traumatic pain, and visceral pain; cognitive impairments and mood disorders associated with the aforementioned disorders;The present invention relates to compounds or compositions of the present invention for use in the prevention or treatment of eye diseases, such as ocular hypertension, glaucoma, normal-tension glaucoma, neurodegenerative conditions of the retina and optic nerve, retinal dystrophy, age-related macular degeneration, and eye conditions, such as conjunctivitis, keratoconjunctivitis sicca, and vernal keratoconjunctivitis, inflammation and / or neurodegeneration; and injuries resulting from traumatic brain injury, seizures, stroke, ischemia, spinal cord injury, cerebral hypoxia, cerebral hemorrhage, or intracranial hematoma.

[0138] In particular, the present invention applies to certain neurological and psychiatric disorders, such as anxiety disorders, but not limited to phobias, generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder (OCD), and acute and chronic stress-related disorders (e.g., post-traumatic stress disorder). The present invention relates to compounds or compositions of the present invention for use in the prevention or treatment of disorders such as: PTSD; mood disorders, for example, but not limited to major depressive disorder, depression and treatment-resistant depression, mania, bipolar disorder; amnesia and other cognitive impairments; disorders usually first diagnosed in infancy, childhood, or adolescence, for example, but not limited to: attention deficit disorders, for example, attention deficit hyperactivity disorder, intellectual disability, learning disability, autism spectrum disorder (e.g., Rett syndrome or fragile X syndrome); drug-related disorders, for example, but not limited to: alcohol dependence, alcohol abuse, drug dependence, and drug abuse; schizophrenia and other mental disorders; somatoform disorders; sleep disorders; muscle spasms and muscle spasm-related disorders, for example, tremors, epilepsy, convulsions, migraines; and traumatic brain injury.

[0139] In particular, the present invention relates to compounds or compositions of the present invention for use in the prevention or treatment of specific neurodegenerative conditions or diseases, such as mild cognitive impairment, dementia, Alzheimer's disease, and Parkinson's disease.

[0140] In particular, the present invention relates to compounds or compositions of the present invention for use in the prevention or treatment of specific pain conditions or diseases, such as acute pain, chronic pain, neuropathic pain, post-traumatic pain, and visceral pain.

[0141] In particular, the present invention relates to compounds or compositions of the present invention for use in the prevention or treatment of hearing impairments, such as age-related hearing loss (or presbycusis), noise-induced hearing loss, cisplatin-induced hearing loss, aminoglycoside-induced hearing loss, acute and chronic tinnitus, central auditory processing disorders, and vestibular disorders.

[0142] Furthermore, the present invention relates to compounds or compositions according to the present invention for use in the prevention or treatment of anxiety disorders, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, depression, bipolar disorder, schizophrenia, autism spectrum disorder, hearing impairment, and pain.

[0143] All of the diseases mentioned above are considered to be diseases related to glutamate deficiency as defined in this invention.

[0144] As already mentioned above, the term "treatment" does not necessarily mean the complete elimination or prevention of all symptoms, but may also refer to symptomatic treatment or preventive intervention for any of the above disorders. In particular, symptoms that can be treated or prevented include, but are not limited to, cognitive impairment, phobic behavior, hypersensitivity, aggressive behavior, hearing impairment, pain, especially anxiety disorders, acute stress disorder, chronic stress disorder, post-traumatic stress disorder, schizophrenia, hearing impairment, and pain in pain disorders.

[0145] As will be apparent to those skilled in the art, alternative nomenclature, disease classifications, and classification systems exist for the disorders described herein, and these have evolved with advances in medicine and science.

[0146] Furthermore, the present invention relates to the use of the compounds according to the present invention as radiolabeled tracers for imaging metabotropic glutamate receptors, preferably mGluR7, in mammals, such as humans.

[0147] Furthermore, the present invention relates to the use of compounds according to general formulas (I), (II), (III), or their stereoisomers, or their N-oxides, or pharmaceutically acceptable salts or solvates, particularly compounds of formulas (I), (II), (III), or their stereoisomers, or pharmaceutically acceptable salts or solvates, or pharmaceutical compositions according to the present invention, for the treatment or prevention of pathological conditions in mammals, including humans, which are modified or improved by the neuromodulatory effects of the compounds according to the present invention on mGluR, particularly mGluR7, and are used particularly for therapeutic purposes.

[0148] Furthermore, the present invention relates to compounds according to formula (I) for use in the treatment, prevention, improvement, suppression, or reduction of risk of various neurological and psychogenic glutamate dysfunction-related disorders in mammals, including humans, which are modified or improved by the neuromodulatory effect of compounds according to formula (I) on mGlu receptors, particularly mGluR7, according to the present invention.

[0149] Furthermore, the present invention relates to the treatment or prevention of pathological conditions in mammals, including humans, whose treatment or prevention is modified or improved by the neuromodulatory effect of compounds of formula (I) according to the present invention on the mGlu receptor, particularly mGluR7, and more particularly to a method for treatment comprising administering a therapeutically effective amount of a compound of general formulas (I), (II), (III), or its stereoisomer, or its N-oxide, or a pharmaceutically acceptable salt or solvate thereof, particularly a compound of formulas (I), (II), (III), or its stereoisomer, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition according to the present invention, to an individual in need.

[0150] Furthermore, the present invention relates to methods for treating, preventing, improving, suppressing, or reducing the risk of various neurological and psychogenic glutamate dysfunction-related disorders in humans, the treatment or prevention of which is modified or improved by the neuromodulatory effect of compounds of formula (I) according to the present invention on mGlu receptors, particularly mGluR7.

[0151] Furthermore, the present invention relates to compounds according to formulas (I), (II), (III), or their stereoisomers, or their N-oxides, or pharmaceutically acceptable salts or solvates, particularly for the treatment or prevention of any of the above-mentioned diseases, and especially for treatment.

[0152] Furthermore, the present invention relates to compounds of formula (I), (II), (III), or their stereoisomers, or their N-oxides, or pharmaceutically acceptable salts or solvates thereof, particularly in the preparation of pharmaceuticals for the treatment or prevention of any of the above-mentioned diseases, and especially to the preparation of pharmaceuticals for the treatment of any of the above-mentioned diseases. This relates to the use of compounds, their stereoisomers, or pharmaceutically acceptable salts or solvates thereof.

[0153] The compounds of the present invention can be administered to mammals, preferably humans, for the treatment or prevention of any of the diseases described above.

[0154] Accordingly, the present invention also relates to a method for the prevention and / or treatment of any of the diseases described above, comprising administering a therapeutically effective amount of the compound according to the present invention to a patient in need thereof.

[0155] As those skilled in the art will understand, the therapeutically effective dose of the compound of the present invention refers to an amount sufficient to modulate, inhibit, or reduce the activity of mGluR, particularly mGluR7. Such a dose will vary depending on the type of disease, the concentration of the compound in the therapeutic formulation, and the patient's condition. Generally, the amount of the compound administered as a therapeutic agent to treat diseases in which the modulation, inhibition, or reduction of mGluR activity, preferably mGluR7 activity, is beneficial, such as the disorders described herein, will be determined on a case-by-case basis by the attending physician.

[0156] Generally, an appropriate dose is one in which the concentration of the compound is in the range of 0.5 nM to 200 μM, more generally 5 nM to 50 μM. To achieve these therapeutic concentrations, it is preferable to administer to patients requiring treatment an effective daily therapeutic dose of approximately 0.01 mg / kg to approximately 50 mg / kg of body weight, preferably approximately 0.01 mg / kg to approximately 25 mg / kg of body weight, more preferably approximately 0.01 mg / kg to approximately 10 mg / kg of body weight, more preferably approximately 0.01 mg / kg to approximately 2.5 mg / kg of body weight, even more preferably approximately 0.05 mg / kg to approximately 1 mg / kg of body weight, and even more preferably approximately 0.1 to approximately 0.5 mg / kg of body weight. Of course, the amount of the compound according to the present invention (sometimes referred to as the active ingredient in this specification) required to achieve the therapeutic effect will vary on a case-by-case basis and will also depend on the specific compound, route of administration, the age and condition of the recipient, and the specific disorder or disease being treated. Furthermore, the treatment method may include administering the active ingredient once to four times a day. In these treatment methods, it is preferable to prescribe the compound according to the present invention before hospitalization. As described below, a suitable pharmaceutical preparation can be prepared using readily available and well-known ingredients by known procedures.

[0157] Combination therapy In the aforementioned diseases or conditions in which the compounds of the present invention or other drugs may be useful, if the compound of the present invention is used in combination with one or more other drugs than the use of one or more drugs alone, the compound of the present invention may be used in combination with such one or more other drugs to treat, prevent, control, improve, or reduce the risk of such diseases or conditions. In another embodiment, the present invention relates to combination therapy in which an active compound according to the present invention is administered together with another active compound. Such combinations may be fixed-dose combinations (i.e., the active ingredients to be combined are in the same pharmaceutical formulation) or free-dose combinations (i.e., the active ingredients to be combined are in different pharmaceutical formulations). That is, a further embodiment of the present invention refers to a combination of each active compound of the present invention, preferably at least one active compound according to the present invention, and another active compound that modulates a receptor or enzyme to improve the efficacy and / or safety of the active compound according to the present invention and / or reduce undesirable side effects. Multiple different drugs in such combinations or products may be combined in a single formulation with a pharmaceutically acceptable carrier or diluent, or may be formulated in different formulations with a pharmaceutically acceptable carrier or diluent.

[0158] A modulator of mGluR, preferably a modulator of mGluR7, containing the compound of the present invention modulates the response of mGluR, preferably the response of mGluR7, to endogenous glutamate and / or mGluR7 agonists and / or group III agonists. Accordingly, the present invention naturally extends to the treatment of disorders related to glutamate dysfunction, and also to treatment by administering an effective amount of an mGluR7 modulator containing the compound of the present invention in combination with an mGluR7 agonist and / or a group III mGluR agonist.

[0159] Furthermore, the compounds of the present invention may be used in combination with psychotherapy in the treatment, prevention, control, improvement, or risk reduction of diseases or conditions in which the compounds of the present invention may be useful.

[0160] The present invention also relates to a pharmaceutical composition according to the present invention, which modulates the activity of mGluR, preferably inhibits or reduces the activity of mGluR, and further comprises another compound. Here, mGluR is preferably mGluR7.

[0161] Furthermore, the present invention is - A pharmaceutical composition comprising at least one compound according to the present invention or at least one compound according to the present invention, - A pharmaceutical composition comprising at least one other compound that modulates the activity of mGluR (preferably mGluR7), preferably inhibiting or reducing the activity of mGluR, and This also applies to kits that include this item.

[0162] dose As is well known to those skilled in the art, the precise dose (or therapeutically effective dose as defined herein) and frequency of administration depend on the type of compound of the present invention used, the type of condition being treated, the severity of the condition, the age, weight, sex, degree of disease, overall health status of the patient, and any other drug therapies the patient may be taking. Naturally, the effective daily dose may also be reduced or increased depending on the patient's response and / or the assessment of the physician prescribing the compound of the present invention.

[0163] This pharmaceutical composition contains, depending on the mode of administration, 0.05 to 99% by mass, preferably 0.1 to 70% by mass, and more preferably 0.1 to 50% by mass of an active ingredient, and 1 to 99.95% by mass, preferably 30 to 99.9% by mass, and more preferably 50 to 99.9% by mass of a pharmaceutically acceptable carrier. All percentages expressed herein are based on the total mass of the composition.

[0164] The amount of the compound according to the present invention, which can be prepared as a single dose in combination with a carrier material, varies depending on the disease being treated, the mammalian species being treated, the specific mode of administration, etc. However, as a general guideline, an appropriate unit dose of the compound according to the present invention is preferably, for example, 0.1 mg to about 1000 mg of the active compound. A preferred unit dose is 1 mg to about 500 mg. A more preferred unit dose is 1 mg to about 300 mg. An even more preferred unit dose is 1 mg to about 100 mg.

[0165] These unit doses can be administered at least twice a day, for example, 2, 3, 4, 5, or 6 times a day, preferably once or twice a day. For an adult weighing 70 kg, the total dose should be adjusted so that the single dose per kg of body weight is in the range of 0.001 to approximately 15 mg. A preferred dose per kg of body weight is 0.01 to approximately 1.5 mg per dose. Such treatment can be continued for several weeks or months, or in some cases, several years. However, naturally, the specific dose level for each individual patient will vary depending on various factors. Such factors, as are well known to those skilled in the art, include, for example, the activity of the specific compound used, the age, weight, overall health status, sex, diet, etc. of the individual being treated, the time and route of administration, the excretion rate, other drugs previously administered to the subject, and the severity of the specific disease being treated.

[0166] Typical dosages include taking tablets containing 1 mg to approximately 100 mg, or 1 mg to approximately 300 mg, once or multiple times a day, or taking sustained-release capsules or tablets containing a relatively high concentration of the active ingredient once a day. The sustained-release effect can be achieved using multiple capsule materials with different pH values ​​for dissolution, capsules or gel formulations that have an osmotic-induced sustained-release effect, or other known controlled-release methods.

[0167] As will be apparent to those skilled in the art, it may be necessary to use dosages outside these ranges in some cases. Furthermore, it should be noted that clinicians or therapists will be familiar with the methods and timing of initiating, interrupting, adjusting, or discontinuing treatment in accordance with the individual patient's response. [Examples]

[0168] Preparation of compounds

[0169] A. Synthesis Method The compounds according to the present invention, particularly those of formulas (I), (II), and (III), can be prepared by methods known to those skilled in the art of organic synthesis, or by using the following synthesis schemes. In all the schemes described below, it is understood that protecting groups for sensitive or reactive groups are used where necessary, in accordance with general principles of organic chemistry. Protecting groups can be handled according to standard methods (TW Green and PGM Wuts, 1991, Protecting Groups in Organic Synthesis, John Wiley & Sons, Inc.). These groups are then removed at an appropriate stage of synthesis by methods well known to those skilled in the art.

[0170] The compounds according to the present invention may be a mixture of enantiomers, which may be separated into R-enantiomers and S-enantiomers. For example, if a specific enantiomer is required, it may be separated from a racemic mixture using, for example, chiral chromatography. Alternatively, it may be prepared by asymmetric synthesis or induction using chiral auxiliary groups, and the resulting diastereomer mixture may be separated. The auxiliary groups can then be cleaved to obtain the desired pure enantiomer. In the case of molecules containing basic functional groups such as amino functional groups or acidic functional groups such as carboxyl functional groups, the separation can be performed by fractional crystallization as a salt of an optically active acid using various solvents, or by other methods known in the literature.

[0171] The final product, intermediate, or starting material can be resolved by any suitable method known in the art (EL Eliel, SH Wilen and LN Mander, 1984, Stereochemistry of Organic Compounds, Wiley-Interscience).

[0172] Among the compounds of formulas (I) to (III), Ar 1 Or Ar 2 Many heterocyclic compounds in which the group is a heteroaromatic or heterocyclic group can be prepared using synthetic routes well known in the art (AR Katrizky and CW Rees, 1984, Comprehensive Heterocyclic Chemistry, Pergamon Press).

[0173] The mGluR modulators disclosed in this invention were prepared using the following synthesis scheme. Specific conditions for carrying out these reactions are shown in the examples below. The synthesis scheme described below illustrates an approach to the compounds of the present invention and should not be construed as the only possible synthetic route to the compounds of the present invention.

[0174] The compounds of formulas (I) to (III) can be converted to their pure enantiomers (+) and (-) by methods such as chiral separation.

[0175] R 9 Compounds of formulas (I), (II), and (III) in which is hydrogen can be obtained according to the following scheme 1. [ka]

[0176] Cyclic ketone intermediate 1 is commercially available. Alternatively, those skilled in organic chemistry can synthesize it using several methods described in the literature.

[0177] Secondary alcohol intermediate 2 is, for example, an organometallic reagent Ar 2 -M (M=Li or MgX) can be obtained by nucleophilic addition. This organometallic reagent can be prepared by metal halide exchange from an aromatic ring having the corresponding appropriate substituent, for example, using nBuLi or iPrMgCl, under an inert atmosphere such as a nitrogen atmosphere, at a controlled temperature such as -78°C, and in an aprotic solvent such as dry THF (step i).

[0178] Intermediate 3 can be formed by further dehydrating intermediate 2, for example, under acidic conditions such as TFA, or in the presence of DCM, at room temperature, or under reflux (step ii).

[0179] The cycloalkenyl ketone intermediate 3 can be converted to the corresponding cycloalkyl ketone intermediate 4 by hydrocracking under a hydrogen atmosphere, under a pressure such as 50 psi, and at a temperature such as 30°C, using a palladium catalyst such as Pd / C (step iii).

[0180] Further reaction of ketone intermediate 4 with POCl3 in the presence of DMF provides chlorocarbonyl intermediate 5 (step iv). This is then subjected to a carbonylation coupling reaction at an appropriate temperature in a solvent such as MeOH, using a CO-releasing reagent such as carbon monoxide, along with a base such as Et3N or AcONa, and a transition metal catalyst such as Pd(dppf)Cl2, or a combination of a catalyst such as Pd(OAc)2 and a ligand such as dppf, to provide lactone intermediate 6 (step v).

[0181] According to Method A of Scheme 1, intermediate 6 is converted to an aryl or heteroarylhydrazine Ar 1 -NH2-NH2 can be reacted with Ar 1 -NH2-NH2 can be a commercially available product, but those skilled in organic chemistry can prepare it in the presence of a catalyst such as PTSA and in a solvent such as toluene or ethyl OH at an appropriate temperature (step ix). This ensures that Y is CH and R 4 , R8 and R 9 The final compounds of formulas (I), (II), and (III) are provided, where R is hydrogen.

[0182] Alternatively, according to Method B of Scheme 1, Intermediate 6 is reacted with hydrazine NH 2 NH 2 in the presence of a solvent such as EtOH using AcOH under acidic conditions and appropriate temperature, or using PTSA in the presence of a solvent such as toluene (Step vii), to provide Intermediate 7. This Intermediate 7 is subjected to a cross-coupling reaction with a (hetero)aromatic halide Ar 1 -X (preferably Ar 1 -Br) at an appropriate temperature, for example, in the presence of a catalyst / ligand system such as Pd2(dba)3 / xantphos, a base such as t-BuOK, and a solvent such as toluene, or by a copper-mediated coupling reaction using CuI and a ligand such as DMEDA or a cyclic diamine ligand in the presence of a base such as K3PO4 and a solvent such as DMF or a mixed solvent such as DMF / dioxane (Step viii), to provide the final compounds of formulas (I), (II), and (III) where Y is CH and R 4 , R 8 and R 9 are hydrogen.

[0183] Alternatively, Intermediate 7 is subjected to a Chan-Lam coupling reaction with a boronic acid or ester Ar 1 -B(OR’)2 in the presence of a catalyst such as Cu(OAc)2 and a base such as pyridine in a solvent such as CH2Cl2 at an appropriate temperature (Step ix) to obtain the final compounds of formulas (I), (II), and (III) where Y is CH and R 4 , R 8 and R 9 are hydrogen.

[0184] Alternatively, according to Method C of Scheme 1, the lactone intermediate 6 can be converted to the ester intermediate 8 using an aqueous NaOH solution, and then alkylated at an appropriate temperature using a haloalkyl reagent (such as ethyl iodide, etc.) in the presence of DMF (Step x). Next, this intermediate 8 can be subjected to Step viii or ix following Step xi, or to Step xii, as described in Steps A and B, to obtain the final compounds of Formulas (I), (II), and (III) in a 1- or 2-step sequence where Y is CH and R 4 and R 8 are hydrogen.

[0185] R 9 compounds of Formulas (I), (II), and (III) where R is hydrogen can be obtained according to Scheme 2 below.

Chemical Formula

[0186] The cyclic ketal intermediate 9 is reacted with POCl3 in the presence of DMF to produce the chlorocarbonyl intermediate 10 (Step i). This intermediate 10 is subjected to a carbonylation coupling reaction at an appropriate temperature using a CO-releasing reagent such as a CO-releasing agent, in the presence of a base such as Et3N or AcONa, in the presence of a transition metal catalyst such as Pd(dppf)Cl2, or using a combination of a catalyst such as Pd(OAc)2 and a ligand such as dppf, in a solvent such as MeOH at an appropriate temperature to obtain the ester-aldehyde intermediate 11 (Step ii). The synthesis of intermediate 12 involves reacting this intermediate 11 with hydrazine NH2NH2 in the presence of a solvent such as EtOH using AcOH, or in the presence of a solvent such as toluene using PTSA, at an appropriate temperature and under acidic conditions (Step iii), and then, in a solvent such as toluene at an appropriate temperature, with an aromatic halide Ar 1 -X (preferably Ar 1A cross-coupling reaction can be carried out with -Br in the presence of a catalyst / ligand system such as Pd2(dba)3 / xanthophos and a base such as t-BuOK, or a copper-mediated coupling reaction can be carried out with CuI using a ligand such as DMEDA or a cyclic diamine ligand in the presence of a base such as K3PO4 and a solvent such as DMF or a mixture of solvents such as DMF / dioxane (step iv).

[0187] Alternatively, intermediate 11 can be mixed with arylhydrazine Ar in the presence of a catalyst such as PTSA and a solvent such as toluene or EtOH. 1 Intermediate 13 may be directly provided by reacting -NH2-NH2 (which may be commercially available or can be prepared by those skilled in organic chemistry) at an appropriate temperature (step v).

[0188] Intermediate 14 is provided by treating intermediate 13 under acidic conditions using TFA or HCl solution, in the presence of a solvent such as acetonitrile or DCM, at an appropriate temperature (step vi). The main triflate intermediate 15 is provided by reacting ketone intermediate 14 with Tf2O at an appropriate temperature in the presence of a base such as Et3N and a solvent such as DCM (step vii).

[0189] According to Method A of Scheme 2, intermediate 15 is converted to boronic acid ester Ar in a solvent such as THF or a dioxane / H2O mixture at an appropriate temperature in the presence of a catalyst / ligand system and bases such as Pd(PPh3)4, Na2CO3, and K2CO3. 1 -B(OR')2 or Ar Boronic Acid 1 Intermediate 16 is provided by subjecting it to a Suzuki cross-coupling reaction using -B(OH)2 (step viiii).

[0190] Alternatively, according to method B of scheme 2, intermediate 17 is provided by reacting intermediate 15 with bis-spinacol-diborane ester in a solvent such as dioxane at a suitable temperature in the presence of a base such as Na2CO3 or K2CO3 and a catalyst system such as Pd(dppf)Cl2 (step x). This intermediate 17 is then reacted with an aromatic halide Ar in a solvent such as dioxane-H2O at a suitable temperature in the presence of a base such as Na2CO3 and a catalyst / ligand system such as Pd(dppf)Cl2. 2 -X (preferably Ar 2 Intermediate 16 is produced by subjecting it to a cross-coupling reaction using -Br (step xi).

[0191] Finally, using palladium hydroxide, intermediate 16 is hydrogenated in the presence of ammonium formate in a solvent such as EtOH at an appropriate temperature, and its cyclic double bond is reduced to obtain the compounds of formulas (I), (II), and (III) (wherein Y is CH and R). 2 and R 8 (is hydrogen.) is provided (step ix).

[0192] The compounds of formulas (I), (II), and (III) can be obtained according to the following scheme 3. [ka]

[0193] The cyclic enone intermediate 18 may be commercially available, but those skilled in organic chemistry can synthesize it using one of several methods described in the literature. This intermediate 18 is then synthesized in the presence of a catalyst / ligand system such as Rh(COD)Cl2, a base such as KOX, a solvent such as dioxane / H2O, at a suitable temperature, under an inert atmosphere, and converted to a boronic acid ester Ar 1 -B(OR')2 or Ar Boronic Acid 1Intermediate 19 is provided by subjecting it to a cross-coupling reaction using -B(OH)2 (step i). Intermediate 20 is produced by reacting this ketone intermediate 19 with POCl3 in the presence of DMF (step ii). Intermediate 20 is subjected to a carbonylation coupling reaction at an appropriate temperature in a solvent such as EtOH, in the presence of a base such as ET3N or AcONa and a transition metal catalyst such as Pd(dppf)Cl2, using a CO-releasing agent such as carbon monoxide, to provide ester-aldehyde intermediate 21 (step iii). Intermediate 21 is subjected to a (hetero)arylhydrazine Ar at an appropriate temperature in the presence of a catalyst such as PTSA and a solvent such as toluene or EtOH. 1 By reacting with -NH2-NH2 (commercially available, but also available to those skilled in organic chemistry) (step iv), the compounds of formulas (I), (II), and (III) are finally obtained (wherein Y is CH and R 2 , R 8 and R 9 It is hydrogen.) is provided.

[0194] Compounds of formulas (I), (II), and (III) (where R 9 ) is hydrogen. ) can be obtained according to the following scheme 4. [ka]

[0195] The cycloalkylene ketone intermediate 18 may be commercially available, but those skilled in organic chemistry can synthesize it using one of several methods described in the literature. This intermediate 18 can be synthesized, for example, in the presence of a transition metal catalyst such as Pd(dppf)Cl2, or in a solvent such as Et3N or Na2CO3, or in the presence of a solvent such as DMSO, at an appropriate temperature, by appropriately substituting it with an aromatic halide Ar 2 -X (preferably Ar 2 -Br or Ar 2 Intermediate 31 can be prepared by cross-coupling reaction with -I) (step i).

[0196] The cycloalkenyl ketone intermediate 31 can be converted to the corresponding ketoester intermediate 34 by a two-step reaction sequence: (step ii) α-carboxylation using cyanoethyl carbonate or diethyl carbonate in an aprotic solvent such as THF in the presence of a base such as LDA or NaH at a controlled temperature such as -78°C, and subsequently (step iii) hydrogenation of the double bond in the presence of a catalyst palladium such as Pd / C, under a hydrogen atmosphere, at a pressure such as 50 psi, and at an appropriate temperature.

[0197] Even if this two-step sequence is carried out in the order of first the hydrogenolysis step (iii) followed by the α-carboxylation step (ii) using the aforementioned conditions, it is still possible to obtain the ketoester intermediate 34.

[0198] Intermediate 35 can be provided by reacting ketoester intermediate 34 with formamidine at an appropriate temperature in the presence of a base such as K2CO3 and a solvent such as EtOH (step iv).

[0199] Intermediate 35 is subjected to a cross-coupling reaction as described in Scheme 1, for example, in the presence of a catalyst / ligand system such as Pd2(dba)3 / xanthophos, a base such as t-BuOK, and a solvent such as toluene, and an aromatic halide Ar 1 -X (preferably Ar 1 By reacting with -Br) or by copper-mediated coupling reaction at an appropriate temperature in a solvent such as DMF or a mixed solvent such as DMF / dioxane in the presence of a base such as K3PO4 using a ligand such as CuI, DMEDA, or a cyclic diamine ligand (step v), the final compounds of formulas (I), (II), and (III) (wherein R 2 , R 7 and R 9 (It is hydrogen.) is provided.

[0200] Ar 2 Compounds of formula (I), (II), or (III) in which are substituted with an OR group can be obtained by the following scheme 5. [ka]

[0201] Compounds of formulas (I), (II), and (III) represented by intermediate 49 (wherein Ar 2 The substituent B is a methoxy group.) is reacted with a dealkylating agent such as boron tribromide in a solvent such as DCM at an appropriate temperature (step i) to provide a hydroxy intermediate 50. This hydroxy functional group is then reacted with an alkyl halide (e.g., R) in a solvent such as DMF at an appropriate temperature in the presence of a base such as Cs2CO3. 2- I, R 2- Br or R 2 By reacting with an alkylating agent such as -Cl (step ii), compounds of formulas (I), (II), and (III) (wherein Ar) are obtained. 2 It is substituted with an oxo group.)

[0202] Ar 1 Compounds of formula (I), (II), or (III) in which are substituted with alkyl, aryl, heteroaryl, amino, or alkoxy radicals can be obtained by the following scheme 6. [ka]

[0203] Intermediate 51 (represented by intermediate 7 in scheme 1 or 35 in scheme 4, but not limited to these) is prepared in the presence of a catalyst / ligand system (e.g., Pd2(dba)3 / xanthophos), a base (e.g., t-BuOK), a solvent (e.g., toluene), and at a suitable temperature, using formula A-Ar 1Intermediate 51 is provided by subjecting it to a cross-coupling reaction using a halo(hetero)aryl of -X (step i). According to method A, intermediate 52, in which A is a halide radical Cl, Br, or I, is further reacted with a boronic acid or boronic acid ester in the presence of a catalyst / ligand system such as Pd(dppf)Cl2 or RuPhos, in the presence of a base such as KOAc or Cs2CO3, in a solvent such as dioxane or dioxane-H2O, at a suitable temperature (step ii), thereby obtaining Ar 1 Compounds of formulas (I), (II), and (III) are provided, wherein the radical is an alkyl, aryl, or heteroaryl radical.

[0204] According to Method B, a similar halide intermediate 52 in which A is a halide radical is heated in a solvent such as dioxane at an appropriate temperature in the presence or absence of a catalyst / ligand system such as Pd(dppf)Cl2 or RuPhos, in the presence of a base such as Na2CO3 or Cs2CO3, and in a solvent such as dioxane. 1 R 2 By reacting with NH (step iii), Ar 1 Compounds of formulas (I), (II), and (III) having an amino group are provided.

[0205] Furthermore, according to method C, intermediate 52 (A is an -OH radical) is reacted with an alkyl halide (RI, R-Br, or R-Cl, etc.) in a solvent such as DMS, in the presence of a base such as Cs2CO3, at an appropriate temperature (step iv), thereby producing Ar 1 Compounds of formulas (I), (II), and (III) having an alkoxy radical are provided.

[0206] Alternatively, Ar 2 Compounds of formulas (I), (II), and (III) having a carboxyl group can be obtained by the following scheme 7. [ka]

[0207] Intermediate 53, where X is Br, is subjected to a cross-coupling reaction using tributyltin ethoxyvinyl in a solvent (e.g., dioxane) at a suitable temperature in the presence of a catalyst / ligand system (e.g., Pd(PPh3)4) and a base (e.g., t-BuOK), followed by hydrolysis in a solvent such as EtOH and an acidic medium such as aqueous HCl to provide intermediate 54. Intermediate 54 is subjected to reduction of the cyclic double bond in the presence of carbon-supported palladium in a solvent such as EtOH and at a suitable temperature in the presence of ammonium formate, etc. (step ii), ultimately yielding intermediate 54 where Y is CH and Ar 2 Compounds of formulas (I), (II), and (III) having an acetyl group are provided.

[0208] B. Laboratory Department An example of a method for preparing the compounds of the present invention is described in the following examples. Unless otherwise specified, all starting materials were obtained from commercial suppliers and used without purification. The following abbreviations may be used in particular in the examples and throughout this specification.

[0209] [Table 1]

[0210] Unless otherwise specified, all temperatures are expressed in degrees Celsius (°C). Unless otherwise specified, all reactions were carried out at room temperature under an inert atmosphere.

[0211] Example 1: 6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one was prepared according to Scheme 1, Method A. [ka]

[0212] Intermediate 2a: 8-(2,4-dimethylphenyl)-1,4-dioxa-spiro[4.5]decane-8-ol According to Scheme 1, step i, n-BuLi (2.5M, 45.39mL, 1.05eq) was added dropwise to a solution of 1-bromo-2,4-dimethylbenzene (20.00g, 108.07 mmol, 1.00eq) in THF (100mL) under an N2 atmosphere, cooled to -70°C. The reaction mixture was stirred at -70°C for 2 hours. Subsequently, a solution of 1,4-dioxa-spiro[4.5]decan-8-one (17.72g, 113.47 mmol, 1.05eq) in THF (100mL) was added dropwise at -70°C, and the reaction mixture was stirred at -70°C for 2 hours. The reaction mixture was quenched with water (300mL) and extracted with siRNA (200mL x 2). The organic layer was dried over Na2SO4 and concentrated under vacuum. The crude product was purified by flash column chromatography using silica gel (PE: siRNA = 10 / 1 to 5 / 1). Intermediate 2a (24.00 g, 86.00 mmol, 79.57% yield) was obtained as a pale yellow solid.

[0213] 1 H NMR (DMSO-d6; 400MHz) δ 7.31-7.29 (m, 1H), 6.90-6.89 (m, 2H), 4.66 (s, 1H), 3.87 (s, 4H), 2.49 (s, 3H), 2.21 (s, 3H), 2.00-1.94 (m, 4H), 1.79-1.76 (m, 2H), 1.53-1.51 (m, 2H).

[0214] Intermediate 3a: 4-(2,4-dimethylphenyl)-cyclohex-3-enone Following Scheme 1, step ii, the solution of intermediate 2a (10.00 g, 38.12 mmol, 1.00 eq) in TFA (500.00 mL) was stirred at 15°C for 1 hour, followed by stirring of the mixture and heating at 80°C for 18 hours. The mixture was vacuum concentrated. The residue was rapidly cooled with saturated NaHCO3 solution, the pH was adjusted to pH 7-8, and extracted with HCl (200 mL x 2). The organic layer was dried over Na2SO4 and vacuum concentrated. The crude product was purified by column chromatography using silica gel (PE: HCl = 10 / 1-5 / 1). Intermediate 3a (11.00 g, 54.92 mmol, 72.04% yield) was obtained as a pale yellow oil.

[0215] 1 H NMR (CDCl3; 400MHz) δ 7.06-6.97 (m, 4H), 6.23-6.18 (m, 1H), 3.95-3.91 (m, 1H), 2.57-2.53 (m, 2H), 2.51 (s, 3H), 2.50-2.33 (m, 4H), 1.99-1.95 (m, 1H).

[0216] Intermediate 4a: 4-(2,4-dimethylphenyl)cyclohexane-1-one Following Scheme 1, step iii, Pd / C (2.00 g, 49.93 mmol, 1.00 eq) was added to a solution of intermediate 3a (10.00 g, 49.93 mmol, 1.00 eq) in SiO2 (100.00 mL) under an N2 atmosphere. This suspension was degassed under vacuum and purged with H2 for several hours. The mixture was stirred under H2 (50 psi) at 30°C for 4 hours. The mixture was filtered, and the filtrate was concentrated under vacuum. Crude intermediate 4a (10.00 g, 49.43 mmol, 99.01% yield) was obtained as a brown solid and used directly in the next step.

[0217] 1H NMR (CDCl3; 400MHz) δ 7.12-7.02 (m, 3H), 3.25-3.22 (m, 1H), 2.57-2.53 (m, 4H), 2.41 (s, 3H), 2.33 (s, 3H), 2.16-2.15 (m, 2H), 1.96-1.94 (m, 2H).

[0218] Intermediate 5a: 2-chloro-5-(2,4-dimethylphenyl)-cyclohex-1-encarbaldehyde Following Scheme 1, step iv, POCl3 (6.82 g, 44.49 mmol, 3.00 eq) was added dropwise to a solution of intermediate 4a (13.01 g, 177.96 mmol, 12.00 eq) in CH2Cl2 (10 mL) at 0°C under an N2 atmosphere. After stirring at 10°C for 1 hour, intermediate 1c (3.00 g, 14.83 mmol, 1.00 eq) in CH2Cl2 (40 mL) was added dropwise. This mixture was stirred at 50°C for 4 hours. The mixture was rapidly cooled with saturated NaHCO3 solution, the pH was adjusted to pH 7-8, and extracted with CH2Cl2 (150 mL x 2). The organic layer was dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography using silica gel (PE / siRNA = 10 / 1) to obtain intermediate 5a (1.70 g, 6.83 mmol, 46.06% yield) as a yellow oily substance.

[0219] 1 H NMR (400MHz, CDCl3) δ 10.25 (s, 1H), 7.09-6.95 (m, 3H), 3.03-2.73 (m, 4H), 2.32 (d, J = 2.6 Hz, 6H), 2.23-2.06 (m, 1H), 2.05-1.90 (m, 2H).

[0220] Intermediate 6a: 5-(2,4-dimethylphenyl)-3-methoxy-4,5,6,7-tetrahydroisobenzofuran-1(3H)-one According to Scheme 1, step v, intermediate 5a (500.00 mg, 2.01 mmol, 1.00 eq), Pd(dppf)Cl2 (147.08 mg, 201.01 μmol, 0.10 eq), and Et3N (610.19 mg, 6.03 mmol, 3.00 eq) were mixed in MeOH (10.00 mL) under an N2 atmosphere. This suspension was degassed under vacuum and purged with CO for several hours. This mixture was stirred at 90°C for 12 hours under a CO atmosphere (1 MPa). This mixture was filtered, and the filtrate was concentrated under vacuum. Intermediate 6a (650.00 mg, crude) was obtained as a brown solid.

[0221] 1 H NMR: (400MHz, CDCl3) δ 7.09-6.98 (m, 3H), 5.67 (s, 1H), 3.60 (s, 3H), 3.19-3.05 (m, 1H), 2.70-2.59 (m, 1H), 2.57-2.44 (m, 2H), 2.33 (s, 3H), 2.31 (s, 3H), 2.06-1.95 (m, 1H), 1.88-1.76 (m, 1H).

[0222] Example 1: 6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one Following Scheme 1, Method A, Step vi, a mixture of intermediate 6a (200.00 mg, 734.38 μmol, 1.00 eq) and pyridine-2-yl-hydrazine hydrochloride (160.28 mg, 1.47 mmol, 2.00 eq) in toluene (10.00 mL) was stirred and heated at 110°C for 8 hours. The mixture was vacuum concentrated. The residue was dissolved in HCl (100 mL) and water (100 mL) and extracted with HCl (100 mL × 2). The organic layer was dried over Na₂SO₄ and vacuum concentrated. The crude product was purified by preparative HPLC to obtain Example 1 (30.00 mg, 90.52 μmol, 6.16% yield) as a brown solid.

[0223] 1H-NMR (400 MHz, CDCl3) δ 8.67 (d, J = 4.0 Hz, 1H), 7.82 - 7.91 (m, 1H), 7.69 - 7.77 (m, 2H), 7.33 - 7.39 (m, 1H), 6.99 - 7.15 (m, 3H), 3.09 - 321 (m, 1H), 2.99 (d, J = 17.6 Hz, 1H), 2.76 - 2.86 (m, 1H), 2.59 - 2.75 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.08 - 2.19 (m, 1H), 1.80 - 1.95 (m, 1H).

[0224] Example 2: (6-(3-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method A. [ka]

[0225] Intermediate 6b: 3-Methoxy-5-(3-methoxyphenyl)-4,5,6,7-tetrahydroisobenzofuran-1(3H)-one Following Scheme 1, steps i-v, intermediate 6b was prepared using 1-bromo-3-methoxybenzene as the starting material, in the same manner as intermediate 6a in Example 1, and obtained as a brown liquid with a total yield of 19%. m / z(M+H) + = 275.1.

[0226] Example 2: 6-(3-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, Method A, Step vi, Example 2 was prepared according to Example 1, using intermediate 6b (800.00 mg, 832.35 μmol) as the starting material and pyridine-2-yl-hydrazine hydrochloride (181.77 mg, 1.25 mmol), and obtained as a yellow solid (8.20 mg, 24.60 μmol).

[0227] 1 H-NMR (400 MHz, MeOD) δ 8.62-8.61 (m, 1H), 8.08-8.05 (m, 1H), 7.90(s,1H), 7.69-7.67(m,1H),7.62-7.56(m,1H),7.29-7.27(m,1H), 6.94-6.90(m, 2H). 6.83-6.84(1H), 3.07-2.86 (m, 4H), 2.68-2.57 (m, 1H), 1.99-1.96 (m, 1H), 1.96-1.93 (m, 1H).

[0228] Example 3: 6-(4-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method A. [ka]

[0229] Intermediate 6c: 3-Methoxy-5-(4-Methoxyphenyl)-4,5,6,7-Tetrahydroisobenzofuran-1(3H)-one Following Scheme 1, steps i-v, intermediate 6c was prepared using 1-bromo-4-methoxybenzene as the starting material, similar to intermediate 6a in Example 1, and was obtained as a brown liquid with a total yield of 14%.

[0230] 1 H NMR (MeOD; 400MHz) δ 7.22-7.20 (m, 2H), 6.91-6.87(m, 2H), 5.88 (s, 1H), 3.93-3.91 (m, 1H), 3.83-3.81(m,1H), 3.77-3.80 (m, 3H), 2.95-2.85 (m, 1H), 2.64-2.59 (m, 1H), 2.31-2.42 (m, 3H), 2.05-2.03 (m, 1H), 1.85- 1.80 (m,1H), 1.30-1.25 (m, 3H).

[0231] Example 3: 6-(4-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, Method A, Step vi, Example 3 was prepared according to Example 1, using intermediate 6c (200.00 mg, 693.63 μmol) and pyridine-2-yl-hydrazine hydrochloride (201.97 mg, 1.39 mmol) as starting materials, and Example 3 was obtained as a green solid (26.00 mg, 77.99 μmol).

[0232] 1 H-NMR (400 MHz, DMSO-d6) δ 8.61-8.60 (m, 1H), 8.04-8.00(m,1H), 7.59-7.56(m, 2H), 7.30-7.23(m,2H), 6.93-6.90(m,2H), 3.70 (s, 3H), 292-2.73 (m, 5H), 2.05-2.02 (m, 1H), 1.85-1.82(m, 1H),1.81-1.78 (m, 1H).

[0233] Example 4: (-)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one and Example 5: (+)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one [ka]

[0234] By separating the enantiomers (400 mg) constituting racemic Example 1 by prepared SFC, (-)6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one Example 4 (72 mg, 18%) was obtained with a 100% excess of enantiomers, and (+)6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one Example 5 (59 mg, 15%) was obtained with a 99% excess of enantiomers, both as yellow solids.

[0235] Example 4: 1 H-NMR (400 MHz, CDCl3) δ 8.67 (br.s., 1H), 7.82 - 7.91 (m, 1H), 7.69 - 7.77 (m, 2H), 7.33 - 7.39 (m, 1H), 6.99 - 7.15 (m, 3H), 3.09 - 321 (m, 1H), 2.99 (d, J = 17.6 Hz, 1H), 2.76 - 2.86 (m, 1H), 2.59 - 2.75 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.08 - 2.19 (m, 1H), 1.80 - 1.95 (m, 1H).

[0236] Example 5: 1 H-NMR (400 MHz, CDCl3) δ 8.67 (br.s., 1H), 7.82 - 7.91 (m, 1H), 7.69 - 7.77 (m, 2H), 7.33 - 7.39 (m, 1H), 6.99 - 7.15 (m, 3H), 3.09 - 321 (m, 1H), 2.99 (d, J = 17.6 Hz, 1H), 2.76 - 2.86 (m, 1H), 2.59 - 2.75 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.08 - 2.19 (m, 1H), 1.80 - 1.95 (m, 1H).

[0237] Example 6: 6-(2,4-dimethylphenyl)-2-(5-chloropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0238] Intermediate 7a: 6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step vii, intermediate 6a (1.2 g, 4.19 mmol, 1 eq) was dissolved in EtOH (10 mL) and AcOH (1 mL), to which N2H4.H2O (427.66 mg, 8.37 mmol, 415.20 μL, 2.0 eq) was added. This mixture was stirred at 80°C for 3 hours and then cooled to 0°C. The resulting white solid was collected after filtration. Intermediate 7a (830 mg, 3.26 mmol, 77.96% yield) was obtained as a white solid.

[0239] 1 H NMR (400MHz, DMSO-d6) δ 12.74 (s, 1H), 7.64 (s, 1H), 7.15-7.08 (m, 1H), 7.03-6.93 (m, 2H), 3.09-2.93 (m, 1H), 2.74-2.57 (m, 3H), 2.47-2.37 (m, 1H), 2.28 (s, 3H), 2.24 (s, 3H), 1.96-1.85 (m, 1H), 1.83-1.68 (m, 1H).

[0240] Example 6: 6-(2,4-dimethylphenyl)-2-(6-chloropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step viii, to a solution of intermediate 7a (100.00 mg, 353.87 μmol, 1.00 eq) in DMF (5.00 mL), 5-chloro-2-bromopyridine (204.30 mg, 1.06 mmol, 3.00 eq), DMEDA (18.72 mg, 212.32 μmol, 22.82 μL, 0.60 eq), CuI (33.70 mg, 176.94 μmol, 0.50 eq), and K3PO4 (187.79 mg, 884.68 μmol, 2.50 eq) were added at 20°C under an N2 atmosphere. Next, this mixture was heated to 110°C and stirred for 12 hours. The reaction product was filtered, and the filtrate was acidified to pH=5 with 12 M HCl aqueous solution and filtered. This filtrate was purified by preparative HPLC to obtain Example 6 (71.93 mg, 196.61 μmol, 55.56% yield) as a grayish-yellow solid.

[0241] 1 H-NMR (400 MHz, CDCl3) δ 8.62 (d, J=2.3 Hz, 1H), 7.87 - 7.82 (m, 1H), 7.78 - 7.73 (m, 2H), 7.14 - 7.09 (m, 1H), 7.08 - 7.04 (m, 2H), 3.20 - 3.11 (m, 1H), 3.04 - 2.95 (m, 1H), 2.87 - 2.78 (m, 1H), 2.77 - 2.60 (m, 2H), 2.34 (s, 3H), 2.33 (s, 3H), 2.20 - 2.11 (m, 1H), 1.95 - 1.83 (m, 1H).

[0242] Example 7: 2-(4-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0243] According to Scheme 1, step viii, Example 7 was prepared according to Example 6 using intermediate 7a (150.00 mg, 530.81 μmol) and 2-bromo-4-chloropyridine (306.45 mg, 1.59 mmol) as starting materials, and Example 7 (178.10 mg, 484.85 μmol, 91.34% yield) was obtained as a brown solid.

[0244] 1 H-NMR (400 MHz, CDCl3) δ 8.49 (d, J=5.4 Hz, 1H), 7.75 (d, J=1.6 Hz, 1H), 7.66 (s, 1H), 7.29 (dd, J=1.8, 5.3 Hz, 1H), 7.05 - 7.00 (m, 1H), 6.99 - 6.94 (m, 2H), 3.12 - 3.02 (m, 1H), 2.96 - 2.86 (m, 1H), 2.80 - 2.69 (m, 1H), 2.67 - 2.53 (m, 2H), 2.28 (s, 3H), 2.25 (s, 3H), 2.10 - 2.02 (m, 1H), 1.86 - 1.74 (m, 1H).

[0245] Example 8: 2-(3-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0246] According to Scheme 1, step viii, Example 8 was prepared according to Example 6 using intermediate 7a (200.00 mg, 707.74 μmol) and 2-bromo-3-chloropyridine (408.59 mg, 2.12 mmol) as starting materials, and Example 8 (24.40 mg, 66.69 μmol, 9.42% yield) was obtained as a grayish-yellow solid.

[0247] 1H-NMR (400 MHz, CDCl3) δ 8.58 (dd, J=1.6, 4.7 Hz, 1H), 7.95 (dd, J=1.5, 8.0 Hz, 1H), 7.72 (s, 1H), 7.44 (dd, J=4.6, 8.0 Hz, 1H), 7.16 - 7.11 (m, 1H), 7.10 - 7.04 (m, 2H), 3.17 (br s, 1H), 3.02 (br d, J=19.6 Hz, 1H), 2.89 - 2.78 (m, 1H), 2.78 - 2.61 (m, 2H), 2.38 (s, 3H), 2.34 (s, 3H), 2.20 - 2.10 (m, 1H), 1.91 (br s, 1H).

[0248] Example 9: 6-(2,4-dimethylphenyl)-2-(6-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0249] According to Scheme 1, step viiii, Example 9 was prepared according to Example 6 using intermediate 7a (70.00 mg, 275.23 μmol) and 2-bromo-6-fluoropyridine (145.31 mg, 825.69 μmol) as starting materials, and Example 9 (32.00 mg, 91.59 μmol, 33% yield) was obtained as a yellow solid.

[0250] 1 H-NMR (400 MHz, DMSO-d6) δ 8.23-8.21 (m, 1H), 7.88 (s,1H), 7.61-7.59 (m,1H), 7.36-7.34 (m,1H), 7.16-7.13 (m,1H), 7.02-7.00(m,2H).

[0251] Example 10: 6-(2,4-dimethylphenyl)-2-(5-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0252] According to Scheme 1, step viiii, Example 10 was prepared according to Example 6 using intermediate 7a (70.00 mg, 275.23 μmol) and 2-bromo-5-fluoropyridine (145.31 mg, 825.69 μmol) as starting materials, and Example 10 (32.00 mg, 91.59 μmol, 23% yield) was obtained as a yellow solid.

[0253] 1 H-NMR (400 MHz, DMSO-d6) δ 8.62-8.61 (m, 1H), 7.97-7.95 (m,1H), 7.86 (s,1H), 7.71-7.67 (m,1H), 7.16-7.14 (m,1H), 7.02-7.00 (m,2H), 3.10-3.07 (m,1H), 2.84-2.70 (m,4H), 2,30 (s,3H), 2.25 (s,3H), 1.94-1.84 (m,1H), 1.83-1.81 (m,1H).

[0254] Example 11: 6-(2,4-dimethylphenyl)-2-(4-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0255] According to Scheme 1, step viii, Example 11 was prepared according to Example 6 using intermediate 7a (60.00 mg, 235.91 μmol) and 2-bromo-4-fluoropyridine (103.79 mg, 589.78 μmol) as starting materials, and Example 11 (24.00 mg, 68.69 μmol, 29% yield) was obtained as a yellow solid.

[0256] 1 H-NMR (400 MHz, DMSO-d6) δ 8.66 (s,1H), 7.88 (s,1H), 7.66-7.61 (m,1H), 7.53-7.51 (m,1H), 7.16-7.14 (m,1H), 7.03-7.00 (m,2H), 3.08-3.01 (m,1H), 2.84-2.58 (m,4H), 2.30 (s,3H), 2.25 (s,3H), 1.94-1.84 (m,1H), 1.83-1.81 (m,1H).

[0257] Example 12: 6-(2,4-dimethylphenyl)-2-(3-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0258] According to Scheme 1, step viiii, Example 12 was prepared according to Example 6 using intermediate 7a (90.00 mg, 353.87 μmol) and 2-bromo-3-fluoropyridine (186.83 mg, 1.06 mmol) as starting materials, and Example 12 (15.00 mg, 42.93 μmol, 12% yield) was obtained as a yellow solid.

[0259] 1H-NMR (400 MHz, DMSO-d6) δ 8.50-8.48 (m,1H), 8.06-8.01 (m,1H), 7.92 (s,1H), 7.72-7.70(s, 1H), 7.17-7.14 (m,1H), 7.02-7.00 (m,2H), 3.11-3.05 (m,1H), 2.86-2.68 (m,4H), 2.34 (s,3H), 2.27 (s,3H), 1.94-1.83 (m,2H).

[0260] Example 13: 6-(2,4-dimethylphenyl)-2-(6-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0261] According to Scheme 1, step viii, Example 13 was prepared according to Example 6 using intermediate 7a (70.00 mg, 275.23 μmol) and 2-bromo-4-methoxypyrimidine (129.37 mg, 688.08 μmol, 84.56 μL) as starting materials, and Example 13 (45.00 mg, 124.50 μmol, 45% yield) was obtained as a yellow solid.

[0262] 1 H-NMR (400 MHz, DMSO-d6) δ 7.93-7.84 (m,1H), 7.84 (s,1H), 7.16-7.12(m, 2H), 7.02-7.00(m,2H), 6.96-6.94 (m,1H), 3.83 (s,3H), 3.10-3.07 (m,1H), 2.81-2.66 (m,4H), 2.31 (s,3H), 2.25 (s,3H), 1.95-1.93 (m,1H), 1.83-1.80 (m,1H).

[0263] Example 14: 6-(2,4-dimethylphenyl)-2-(5-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0264] According to Scheme 1, step viii, Example 14 was prepared according to Example 6 using intermediate 7a (70.00 mg, 275.23 μmol) and 2-bromo-5-methoxypyrimidine (129.37 mg, 688.08 μmol) as starting materials, and Example 14 (30.00 mg, 83.00 μmol, 30.16% yield) was obtained as a yellow solid.

[0265] 1 H-NMR (400 MHz, DMSO-d6) δ 8.28-8.27 (m,1H), 7.82 (s,1H), 7.60-7.59(m,1H), 7.58-7.57 (m,1H), 7.16-7.13 (m,1H), 7.02-7.00 (m,2H), 3.91 (s,3H), 3.10-3.07 (m,1H), 2.93-2.55 (m,4H), 2.31 (s,3H), 2.25 (s,3H), 1.93-1.90 (m,1H), 1.84-1.80 (m,1H).

[0266] Example 15: 6-(2,4-dimethylphenyl)-2-(4-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0267] Scheme 1. According to step viii, Example 15 was prepared using Intermediate 7a (70.00 mg, 275.23 μmol) and 2-bromo-4-methoxypyrimidine (129.37 mg, 688.08 μmol) as starting materials according to Example 6, and Example 15 (53.00 mg, 146.64 μmol, 53% yield) was obtained as a yellow solid.

[0268] 1 1H-NMR (400 MHz, DMSO-d6) δ 8.41-8.39 (m,1H), 7.83 (s,1H), 7.16-7.10 (m,3H), 7.02-7.00 (m,1H), 3.89 (s,3H), 3.07-3.02 (m,1H), 2.78-2.66 (m,4H), 2.30 (s,3H), 2.25 (s,3H), 1.93-1.83 (m,1H), 1.82-1.80 (m,1H).

[0269] Example 16: 6-(2,4-Dimethylphenyl)-2-(3-methoxypyridin-2-yl)-5,6,7,8-tetrahydrophthalazin-1(2H)-one was prepared according to Scheme 1, Method B.

Chemical formula

[0270] Scheme 1. According to step viii, Example 16 was prepared using Intermediate 7a (90.00 mg, 353.87 μmol) and 2-bromo-3-methoxypyrimidine (166.34 mg, 884.68 μmol) as starting materials according to Example 6, and Example 16 (17.00 mg, 47.03 μmol, 13% yield) was obtained as a yellow solid.

[0271] <000,0970>H-NMR (400 MHz, DMSO-d6) δ 8.15-8.13 (m,1H), 7.81 (s,1H), 7.72-7.70 (m,1H), 7.57-7.55 (m,1H), 7.16-7.14 (m,1H), 7.02-7.00 (m,2H), 3.80 (s,3H), 3.10-3.07(m,1H), 2.82-2.67 (m,4H), 2.31 (s,3H), 2.25 (s,3H), 1.92-1.81 (m,2H).

[0272] Example 17: 6-(2,4-dimethylphenyl)-2-(6-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0273] According to Scheme 1, step viiii, Example 17 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromo-6-methylpyridine (146.10 mg, 849.30 μmol, 96.75 μL) as starting materials, and Example 17 (59.06 mg, 170.97 μmol, 60.39% yield) was obtained as a grayish-yellow solid.

[0274] 1 H-NMR (400 MHz, CDCl3) δ 7.81 - 7.69 (m, 2H), 7.45 (d, J=7.9 Hz, 1H), 7.24 (d, J=7.7 Hz, 1H), 7.12 - 7.08 (m, 1H), 7.07 - 7.02 (m, 2H), 3.19 - 3.08 (m, 1H), 3.03 - 2.92 (m, 1H), 2.86 - 2.76 (m, 1H), 2.73 - 2.59 (m, 5H), 2.35 (s, 3H), 2.32 (s, 3H), 2.12 (td, J=2.9, 10.4Hz, 1H), 1.94 - 1.80 (m, 1H).

[0275] Example 18: 6-(2,4-dimethylphenyl)-2-(5-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0276] According to Scheme 1, step viiii, Example 18 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromo-5-methylpyridine (146.10 mg, 849.30 μmol) as starting materials, and Example 18 (52.33 mg, 151.49 μmol, 53.51% yield) was obtained as a grayish-yellow solid.

[0277] 1 H-NMR (400 MHz, CDCl3) δ 8.49 (d, J=1.5 Hz, 1H), 7.73 (s, 1H), 7.71 - 7.66 (m, 1H), 7.64 - 7.60 (m, 1H), 7.14 - 7.10 (m, 1H), 7.08 - 7.04 (m, 2H), 3.21 - 3.09 (m, 1H), 3.06 - 2.94 (m, 1H), 2.87 - 2.77 (m, 1H), 2.76 - 2.60 (m, 2H), 2.43 (s, 3H), 2.37 (s, 3H), 2.34 (s, 3H), 2.19 - 2.09 (m, 1H), 1.96 - 1.81 (m, 1H).

[0278] Example 19: 6-(2,4-dimethylphenyl)-2-(4-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0279] According to Scheme 1, step viiii, Example 19 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromo-4-methylpyridine (146.10 mg, 849.30 μmol, 94.26 μL) as starting materials, and Example 19 (69.51 mg, 201.22 μmol, 71.08% yield) was obtained as a white solid.

[0280] 1 H-NMR (400 MHz, CDCl3) δ 8.53 (d, J=5.1 Hz, 1H), 7.74 (s, 1H), 7.56 (s, 1H), 7.14 - 7.10 (m, 1H), 7.08 - 7.04 (m, 1H), 7.08 - 7.04 (m, 2H), 3.22 - 3.07 (m, 1H), 3.06 - 2.95 (m, 1H), 2.87 - 2.78 (m, 1H), 2.76 - 2.61 (m, 2H), 2.47 (s, 3H), 2.37 (s, 3H), 2.34 (s, 3H), 2.20 - 2.09 (m, 1H), 1.97 - 1.80 (m, 1H).

[0281] Example 20: 6-(2,4-dimethylphenyl)-2-(3-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0282] According to Scheme 1, step viiii, Example 20 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromo-3-methylpyridine (146.09 mg, 849.30 μmol) as starting materials, and Example 20 (8.60 mg, 24.75 μmol, 8.74% yield) was obtained as a grayish-yellow solid.

[0283] 1H-NMR (400 MHz, CDCl3) δ 8.55 - 8.44 (m, 1H), 7.74 (d, J=6.7 Hz, 1H), 7.71 (s, 1H), 7.36 (dd, J=4.8, 7.7 Hz, 1H), 7.16 - 7.11 (m, 1H), 7.10 - 7.04 (m, 2H), 3.16 (br s, 1H), 3.07 - 2.94 (m, 1H), 2.88 - 2.78 (m, 1H), 2.77 - 2.61 (m, 2H), 2.38 (s, 3H), 2.36 - 2.33 (m, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 2.20 - 2.09 (m, 1H), 1.98 - 1.83 (m, 1H).

[0284] Example 21: 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)picolinonitrile was prepared according to Scheme 1, Method B. [ka]

[0285] According to Scheme 1, step viiii, Example 21 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 6-bromopicolinonitrile (155.43 mg, 849.30 μmol) as starting materials, and Example 21 (53.43 mg, 146.31 μmol, 51.68% yield) was obtained as a white solid.

[0286] 1H-NMR (400 MHz, CDCl3) δ 8.05 - 7.99 (m, 2H), 7.81 - 7.75 (m, 2H), 7.13 - 7.10 (m, 1H), 7.08 - 7.05 (m, 2H), 3.21 - 3.11 (m, 1H), 2.99 (br dd, J=5.3, 19.1 Hz, 1H), 2.89 - 2.80 (m, 1H), 2.78 - 2.59 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.20 - 2.11 (m, 1H), 1.96 - 1.82 (m, 1H).

[0287] Example 22: 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile was prepared according to Scheme 1, Method B. [ka]

[0288] According to Scheme 1, step viiii, Example 22 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 6-bromonicotinonitrile (155.43 mg, 849.30 μmol) as starting materials, and Example 22 (21.19 mg, 59.45 μmol, 21.00% yield) was obtained as a white solid.

[0289] 1 H-NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.03 (d, J=2.3 Hz, 1H), 7.98 - 7.91 (m, 1H), 7.73 - 7.67 (m, 1H), 6.98 (d, J=17.4 Hz, 3H), 3.13 - 3.01 (m, 1H), 2.97 - 2.85 (m, 1H), 2.79 - 2.70 (m, 1H), 2.68 - 2.52 (m, 2H), 2.27 (s, 3H), 2.25 (s, 3H), 2.11 - 2.02 (m, 1H), 1.87 - 1.74 (m, 1H).

[0290] Example 23: 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)isonicotinonitrile was prepared according to Scheme 1, Method B. [ka]

[0291] According to Scheme 1, step viii, Example 23 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromoisonicotinonitrile (17.27 mg, 94.37 μmol) as starting materials, and Example 23 (28.72 mg, 80.58 μmol, 28.46% yield) was obtained as a white solid.

[0292] 1 H-NMR (400 MHz, CDCl3) δ 8.85 (d, J=4.4 Hz, 1H), 8.13 (s, 1H), 7.78 (s, 1H), 7.59 (dd, J=1.3, 5.0 Hz, 1H), 7.16 - 7.03 (m, 3H), 3.22 - 3.12 (m, 1H), 3.06 - 2.96 (m, 1H), 2.89 - 2.80 (m, 1H), 2.79 - 2.62 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.21 - 2.12 (m, 1H), 1.98 - 1.83 (m, 1H).

[0293] Example 24: 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile was prepared according to Scheme 1, Method B. [ka]

[0294] According to Scheme 1, step viii, Example 24 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromonicotinonitrile (155.43 mg, 849.30 μmol) as starting materials, and Example 24 (8.80 mg, 24.69 μmol, 8.72% yield) was obtained as a white solid.

[0295] 1 H-NMR (400 MHz, CDCl3) δ 8.88 (d, J=5.0 Hz, 1H), 8.20 (d, J=7.9 Hz, 1H), 7.75 (s, 1H), 7.61 - 7.52 (m, 1H), 7.15 - 7.04 (m, 3H), 3.22 - 3.13 (m, 1H), 3.08 - 3.00 (m, 1H), 2.88 - 2.79 (m, 1H), 2.78 - 2.64 (m, 2H), 2.38 (s, 3H), 2.34 (s, 3H), 2.15 (br s, 1H), 1.99 - 1.83 (m, 1H).

[0296] Example 25: 6-(2,4-dimethylphenyl)-2-(5-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0297] According to Scheme 1, step viiii, Example 25 was prepared according to Example 6 using intermediate 7a (100.00 mg, 353.87 μmol) and 6-bromo-3-hydroxypyridine (184.72 mg, 1.06 mmol) as starting materials, and Example 25 (42.10 mg, 115.12 μmol, 32.53% yield) was obtained as a grayish-white solid.

[0298] 1H-NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.24 (dd, J=1.8, 4.8 Hz, 1H), 7.87 (dd, J=1.6, 7.8 Hz, 1H), 7.19 (dd, J=4.8, 7.8 Hz, 1H), 7.15 - 7.11 (m, 1H), 7.09 - 7.04 (m, 2H), 3.26 - 3.16 (m, 1H), 3.15 - 3.06 (m, 1H), 3.04 - 2.96 (m, 1H), 2.92 - 2.80 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.24 - 2.14 (m, 1H), 2.04 - 1.95 (m, 1H).

[0299] Example 26: 6-(2,4-dimethylphenyl)-2-(4-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0300] To a solution of compound Example 15 (200.00 mg, 553.34 μmol, 1.00 eq) in CH2Cl2 (5.00 mL), BBr3 (693.11 mg, 2.77 mmol, 266.58 μL, 5.00 eq) was added. This mixture was stirred at 40°C for 12 hours, and the desired product was detected. This mixture was added to water (30 mL) and extracted with ethyl acetate (30 mL x 3). The organic layer was dried over Na2SO4, filtered, concentrated under reduced pressure, and the residue was purified by preparative TLC (PE:Â=0:1). Example 26 (130.00 mg, 370.46 μmol, 66.95% yield) was obtained as a white solid.

[0301] 1H-NMR (400 MHz, DMSO-d6) δ 8.26 (br d, J=4.5 Hz, 1H), 7.81 (s, 1H), 7.15 (br d, J=7.9 Hz, 1H), 7.05 - 6.96 (m, 2H), 6.86 (br s, 2H), 3.07 (br s, 1H), 2.85 - 2.59 (m, 3H), 2.58 - 2.53 (m, 1H), 2.31 (s, 3H), 2.25 (s, 3H), 1.93 (br s, 1H), 1.88 - 1.75 (m, 1H).

[0302] Example 27: 6-(2,4-dimethylphenyl)-2-(5-(methoxymethyl)pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0303] According to Scheme 1, step viii, Example 27 was prepared according to Example 6 using intermediate 7a (100.00 mg, 353.87 μmol) and 2-bromo-5-(methoxymethyl)pyridine (214.50 mg, 1.06 mmol) as starting materials, and Example 27 (56.21 mg, 149.71 μmol, 42.31% yield) was obtained as a white solid.

[0304] 1H-NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.24 (dd, J=1.8, 4.8 Hz, 1H), 7.87 (dd, J=1.6, 7.8 Hz, 1H), 7.19 (dd, J=4.8, 7.8 Hz, 1H), 7.15 - 7.11 (m, 1H), 7.09 - 7.04 (m, 2H), 3.26 - 3.16 (m, 1H), 3.15 - 3.06 (m, 1H), 3.04 - 2.96 (m, 1H), 2.92 - 2.80 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.24 - 2.14 (m, 1H), 2.04 - 1.95 (m, 1H).

[0305] Example 28: 6-(2,4-dimethylphenyl)-2-(pyridine-3-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0306] According to Scheme 1, step viiii, Example 28 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 3-bromopyridine (134.19 mg, 849.30 μmol, 81.82 μL) as starting materials, and Example 28 (32.83 mg, 99.06 μmol, 34.99% yield) was obtained as a white solid.

[0307] 1H-NMR (400 MHz, CDCl3) δ 9.04 - 8.91 (m, 1H), 8.63 (br s, 1H), 8.09 (br d, J=8.3 Hz, 1H), 7.73 (d, J=1.9 Hz, 1H), 7.44 (br s, 1H), 7.18 - 7.01 (m, 3H), 3.16 (br s, 1H), 3.02 (br d, J=19.2 Hz, 1H), 2.88 - 2.79 (m, 1H), 2.77 - 2.61 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.17 (br d, J=13.1 Hz, 1H), 1.91 (br d, J=11.8 Hz, 1H).

[0308] Example 29: 6-(2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0309] According to Scheme 1, step viii, Example 29 was prepared according to Example 6 using intermediate 7a (780 mg, 3.07 mmol) and 2-bromopyrimidine (585.11 mg, 3.68 mmol) as starting materials, and Example 29 (383.35 mg, 1.12 mmol, 36.48% yield) was obtained as a white solid.

[0310] 1H-NMR (400 MHz, CDCl3) δ 8.95 (d, J=4.9 Hz, 2H), 7.71 (s, 1H), 7.44 (t, J=4.8 Hz, 1H), 7.14 - 7.10 (m, 1H), 7.08 - 7.04 (m, 2H), 3.21 - 3.11 (m, 1H), 3.08 - 2.98 (m, 1H), 2.87 - 2.78 (m, 1H), 2.76 - 2.63 (m, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.14 (br dd, J=5.8, 13.5 Hz, 1H), 1.95 - 1.83 (m, 1H).

[0311] Example 30: 6-(2,4-dimethylphenyl)-2-(pyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0312] According to Scheme 1, step viiii, Example 30 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 2-bromopyrazine (135.02 mg, 849.30 μmol) as starting materials, and Example 30 (48.17 mg, 144.92 μmol, 51.19% yield) was obtained as a grayish-yellow solid.

[0313] 1H-NMR (400 MHz, CDCl3) δ 9.05 (d, J=1.1 Hz, 1H), 8.60 - 8.50 (m, 1H), 7.69 (s, 1H), 7.05 - 7.01 (m, 1H), 7.00 - 6.94 (m, 2H), 3.13 - 3.02 (m, 1H), 3.13 - 3.02 (m, 1H), 2.98 - 2.87 (m, 1H), 2.80 - 2.71 (m, 1H), 2.69 - 2.54 (m, 2H), 2.28 (s, 3H), 2.25 (s, 3H), 2.12 - 2.02 (m, 1H), 1.88 - 1.74 (m, 1H).

[0314] Example 31: 6-(2,4-dimethylphenyl)-2-(pyrimidine-5-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0315] According to Scheme 1, step viiii, Example 31 was prepared according to Example 6 using intermediate 7a (80.00 mg, 283.10 μmol) and 5-bromopyrimidine (135.02 mg, 849.30 μmol) as starting materials, and Example 31 (24.80 mg, 74.61 μmol, 26.35% yield) was obtained as a brown solid.

[0316] 1 H-NMR (400 MHz, CDCl3) δ 9.23 (s, 2H), 9.19 (s, 1H), 7.74 (s, 1H), 7.12 - 7.08 (m, 1H), 7.08 - 7.03 (m, 2H), 3.20 - 3.10 (m, 1H), 3.06 - 2.95 (m, 1H), 2.87 - 2.77 (m, 1H), 2.76 - 2.60 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.21 - 2.11 (m, 1H), 1.95 - 1.82 (m, 1H).

[0317] Example 32: 6-(2,4-dimethylphenyl)-2-(thiazol-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0318] According to Scheme 1, step viii, Example 32 was prepared according to Example 6 using intermediate 7a (120.00 mg, 471.83 μmol) and 2-bromothiazole (116.08 mg, 707.75 μmol, 63.78 μL) as starting materials, and Example 32 (12.00 mg, 34.51 μmol, 8.76% yield) was obtained as a yellow solid.

[0319] 1 H-NMR (400 MHz, CDCl3) δ 1.84 - 1.96 (m, 1 H) 2.12 - 2.21 (m, 1 H) 2.33 (s, 3 H) 2.36 (s, 3 H) 2.66 - 2.81 (m, 2 H) 2.82 - 2.92 (m, 1 H) 3.07 (br dd, J=19.89, 5.08 Hz, 1 H) 3.12 - 3.20 (m, 1 H) 7.05 (br d, J=5.77 Hz, 2 H) 7.07 - 7.12 (m, 1 H) 7.30 (d, J=3.39 Hz, 1 H) 7.81 (d, J=3.39Hz, 1H) 7.90 (s, 1 H).

[0320] Example 33: 6-(2,4-dimethylphenyl)-2-(thiazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0321] According to Scheme 1, step viii, Example 33 was prepared according to Example 6 using intermediate 7a (80.00 mg, 314.55 μmol) and 4-bromothiazole (77.39 mg, 471.83 μmol, 42.52 μL) as starting materials, and Example 33 (8.00 mg, 23.44 μmol, 7.45% yield) was obtained as a grayish-white solid.

[0322] 1 H-NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.65 (s, 2H), 7.14 (d, J=8.4 Hz, 1H), 7.06 - 6.96 (m, 2H), 3.82 (s, 3H), 3.23 - 3.11 (m, 1H), 2.97 - 2.82 (m, 2H), 2.81 - 2.71 (m, 1H), 2.70 - 2.57 (m, 1H), 2.36 (s, 3H), 2.29 (s, 3H), 2.14 - 2.04 (m, 1H), 1.98 - 1.83 (m, 1H).

[0323] Example 34: 6-(2,4-dimethylphenyl)-2-(1-methyl-1H-imidazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0324] According to Scheme 1, step viii, Example 34 was prepared according to Example 6 using intermediate 7a (100.00 mg, 353.87 μmol) and 4-bromo-1-methyl-1H-imidazole (113.95 mg, 707.74 μmol) as starting materials, and Example 34 (10.61 mg, 31.72 μmol, 8.97% yield) was obtained as a white solid.

[0325] 1H-NMR (400 MHz, MeOD) δ 7.89 (s, 1H), 7.65 (s, 2H), 7.14 (d, J=8.4 Hz, 1H), 7.06 - 6.96 (m, 2H), 3.82 (s, 3H), 3.23 - 3.11 (m, 1H), 2.97 - 2.82 (m, 2H), 2.81 - 2.71 (m, 1H), 2.70 - 2.57 (m, 1H), 2.36 (s, 3H), 2.29 (s, 3H), 2.14 - 2.04 (m, 1H), 1.98 - 1.83 (m, 1H)

[0326] Example 35: 6-(2,4-dimethylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0327] According to Scheme 1, step viiii, Example 35 was prepared according to Example 6 using intermediate 7a (0.2 g, 786.39 μmol) and 2-chloro-4-methoxypyrimidine (136.42 mg, 943.67 μmol) as starting materials, and Example 35 (0.118 g, 323.05 μmol, 41.08% yield) was obtained as a white solid.

[0328] 1 H-NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.74 (s, 1H), 7.15-7.00 (m, 3H), 6.87 (d, J = 5.6 Hz, 1H), 4.06 (s, 3H), 3.21-3.10 (m, 1H), 3.09-3.01 (m, 1H), 2.88-2.79 (m, 1H), 2.77-2.61 (m, 2H), 2.36 (s, 3H), 2.33 (s, 3H), 2.18-2.10 (m, 1H), 1.95 - 1.81 (m, 1H).

[0329] Example 36: 6-(2,4-dimethylphenyl)-2-(4,6-dimethylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0330] According to Scheme 1, step viiii, Example 36 was prepared according to Example 6 using intermediate 7a (0.2 g, 786.39 μmol) and 2-chloro-4,6-dimethylpyrimidine (168.19 mg, 1.18 mmol) as starting materials, and Example 36 (0.034 g, 89.61 μmol, 11.40% yield) was obtained as a white solid.

[0331] 1 H-NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.15 (s, 1H), 7.12-7.07 (m, 1H), 7.06-7.02 (m, 2H), 3.18-3.07 (m, 1H), 2.98-2.90 (m, 1H), 2.85-2.76 (m, 1H), 2.74-2.65 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.16-2.05 (m, 1H), 1.92-1.78 (m, 1H).

[0332] Example 37: 2-(4-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0333] According to Scheme 1, step viiii, Example 37 was prepared according to Example 6 using intermediate 7a (0.2 g, 786.39 μmol) and 2-chloro-4-cyclopropylpyrimidine (145.89 mg, 943.67 μmol) as starting materials, and Example 37 (0.029 g, 77.86 μmol, 9.90% yield) was obtained as a white solid.

[0334] 1 H-NMR (400 MHz, CDCl3) δ 8.64 (d, J = 4.4 Hz, 1H), 7.65 (s, 1H), 7.18 (d, J = 4.8 Hz, 1H), 7.13-7.07 (m, 1H), 7.06-6.97 (m, 2H), 3.14-3.11 (m, 1H), 3.04-2.92 (m, 1H), 2.84-2.74 (m, 1H), 2.69-2.63 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.15-2.08 (m, 2H), 1.92-1.85 (m, 1H), 1.28-1.12 (m, 4H).

[0335] Example 38: 2-(5-hydroxypyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0336] Intermediate 6d: 3-Methoxy-5-(3-Methoxy-2-methylphenyl)-4,5,6,7-tetrahydroisobenzofuran-1(3H)-one Following Scheme 1, steps i-v, intermediate 6d was prepared using 1-bromo-3-methoxy-2-methylbenzene as the starting material, similar to intermediate 6a in Example 1, and obtained as a brown liquid with a total yield of 15%. m / z(M+H) + = 289.1

[0337] Intermediate 7b: 6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 1, step vii, intermediate 7b was prepared using intermediate 6d (21.30 g, 73.87 mmol) as the starting material, similar to intermediate 7a in Example 6, and intermediate 7b (15.30 g, 56.60 mmol, 76.62% yield) was obtained as a white solid.

[0338] 1 H NMR (400 MHz, DMSO-d6) δ 12.76 (br s, 1H), 7.65 (s, 1H), 7.10-7.18 (m, 1H), 6.84 (t, J=8.72 Hz, 2H), 3.77 (s, 3H), 3.10 (br s, 1H), 2.55-2.75 (m, 3H), 2.35-2.47 (m, 1H), 2.15 (s, 3H), 1.90 (br s, 1H), 1.76 (dq, J=4.89, 11.84 Hz, 1H).

[0339] Example 38: 2-(5-hydroxypyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step viiii, Example 38 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 6-bromo-3-hydroxypyridine (115.86 mg, 665.85 μmol) as starting materials, and Example 38 (72.80 mg, 200.12 μmol, 36.07% yield) was obtained as a white solid.

[0340] 1H-NMR (400 MHz, DMSO-d6) δ 10.40 (br s, 1H), 8.04-8.10 (m, 1H), 7.80 (s, 1H), 7.29-7.36 (m, 2H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.65 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 3.78 (s, 3H), 3.09-3.21 (m, 1H), 2.62-2.82 (m, 3H), 2.52-2.59 (m, 1H), 2.17 (s, 3H), 1.89-2.01 (m, 1H), 1.74-1.87 (m, 1H).

[0341] Example 39: 2-(5-(hydroxymethyl)pyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0342] According to Scheme 1, step viiii, Example 39 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and (6-bromopyridine-3-yl)methanol (125.19 mg, 665.86 μmol) as starting materials, and Example 39 (81.97 mg, 216.96 μmol, 39.10% yield) was obtained as a white solid.

[0343] 1H-NMR (400 MHz, DMSO-d6) δ 8.52 (d, J=1.63 Hz, 1H), 7.92 (dd, J=2.20, 8.09 Hz, 1H), 7.84 (s, 1H), 7.52 (d, J=8.16 Hz, 1H), 7.18 (t, J=7.97 Hz, 1H), 6.89 (d, J=7.78 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 5.45 (t, J=5.71 Hz, 1H), 4.62 (d, J=5.52 Hz, 2H), 3.78 (s, 3H), 3.12-3.22 (m, 1H), 2.64-2.86 (m, 3H), 2.55 (br d, J=9.66 Hz, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.78-1.89 (m, 1H).

[0344] Example 40: 6-(3-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0345] According to Scheme 1, step viiii, Example 40 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 5-bromopyrimidine (105.86 mg, 665.86 μmol) as starting materials, and Example 40 (45.56 mg, 128.81 μmol, 23.21% yield) was obtained as a brown solid.

[0346] 1H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J=4.89 Hz, 2H), 7.85 (s, 1H), 7.71 (t, J=4.89 Hz, 1H), 7.14-7.21 (m, 1H), 6.87 (dd, J=7.97, 17.63 Hz, 2H), 3.78 (s, 3H), 3.14-3.24 (m, 1H), 2.78-2.87 (m, 1H), 2.66-2.77 (m, 2H), 2.56 (br d, J=10.04 Hz, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.78-1.91 (m, 1H).

[0347] Example 41: 6-(3-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0348] According to Scheme 1, step viiii, Example 41 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 2-bromo-5-methylpyrimidine (116.51 mg, 665.86 μmol) as starting materials, and Example 41 (75.16 mg, 206.05 μmol, 37.13% yield) was obtained as a white solid.

[0349] 1 H-NMR (400 MHz, DMSO-d6) δ 8.84 (s, 2H), 7.83 (s, 1H), 7.14-7.23 (m, 1H), 6.87 (dd, J=7.91, 16.69 Hz, 2H), 3.78 (s, 3H), 3.13-3.23 (m, 1H), 2.64-2.87 (m, 3H), 2.52-2.60 (m, 1H), 2.38 (s, 3H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.75-1.90 (m, 1H).

[0350] Example 42: 6-(3-methoxy-2-methylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0351] According to Scheme 1, step viii, Example 42 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 2-bromo-4-methoxypyrimidine (125.85 mg, 665.85 μmol) as starting materials, and Example 42 (97.29 mg, 256.84 μmol, 46.29% yield) was obtained as a red solid.

[0352] 1 H-NMR (400 MHz, DMSO-d6) δ 8.69 (d, J=5.77 Hz, 1H), 7.83 (s, 1H), 7.18 (t, J=7.97 Hz, 1H), 7.13 (d, J=5.90 Hz, 1H), 6.89 (d, J=7.65 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 3.93 (s, 3H), 3.78 (s, 3H), 3.13-3.24 (m, 1H), 2.64-2.86 (m, 3H), 2.56 (br d, J=9.41 Hz, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.78-1.90 (m, 1H).

[0353] Example 43: 2-(5-chloropyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0354] According to Scheme 1, step viii, Example 43 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 2-bromo-5-chloropyrimidine (128.80 mg, 665.86 μmol) as starting materials, and Example 43 (98.84 mg, 257.92 μmol, 46.48% yield) was obtained as a white solid.

[0355] 1 H-NMR (400 MHz, DMSO-d6)) δ 9.16 (s, 2H), 7.87 (s, 1H), 7.15-7.20 (m, 1H), 6.89 (d, J=7.65 Hz, 1H), 6.85 (d, J=8.03 Hz, 1H), 3.78 (s, 3H), 3.12-3.24 (m, 1H), 2.78-2.86 (m, 1H), 2.65-2.76 (m, 2H), 2.53-2.61 (m, 1H), 2.18 (s, 3H), 1.91-2.00 (m, 1H), 1.76-1.90 (m, 1H).

[0356] Example 44: 6-(3-methoxy-2-methylphenyl)-2-(5-methoxypyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0357] According to Scheme 1, step viii, Example 44 was prepared according to Example 6 using intermediate 7b (150.00 mg, 554.88 μmol) and 2-bromo-5-methoxypyrazine (125.85 mg, 665.86 μmol) as starting materials, and Example 44 (111.11 mg, 290.09 μmol, 52.28% yield) was obtained as a white solid.

[0358] 1H-NMR (400 MHz, DMSO-d6) δ 8.47 (d, J=1.25 Hz, 1H), 8.35 (d, J=1.25 Hz, 1H), 7.89 (s, 1H), 7.14-7.22 (m, 1H), 6.89 (d, J=7.65 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 3.99 (s, 3H), 3.78 (s, 3H), 3.10-3.22 (m, 1H), 2.64-2.86 (m, 3H), 2.56 (br d, J=9.41 Hz, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.78-1.89 (m, 1H).

[0359] Example 45: 2-(5-hydroxypyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0360] According to Scheme 1, step viii, Example 45 was prepared according to Example 6 using intermediate 7b (450 mg, 1.66 mmol) and 2-bromo-5-hydroxypyrimidine (349.55 mg, 2.00 mmol) as starting materials, and Example 45 (520 mg, 1.43 mmol, 85.72% yield) was obtained as a brown solid.

[0361] 1 H-NMR (400 MHz, DMSO-d6) δ 8.43 (s, 2H), 7.79 (s, 1H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.78 Hz, 1H), 6.85 (d, J=8.28 Hz, 1H), 3.76-3.81 (m, 3H), 3.11-3.25 (m, 1H), 2.67-2.84 (m, 3H), 2.55-2.60 (m, 1H), 2.18 (s, 3H), 1.93 (br s, 1H), 1.76-1.89 (m, 1H).

[0362] Example 46: 6-(3-methoxy-2-methylphenyl)-2-(4-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0363] According to Scheme 1, step viii, Example 46 was prepared according to Example 6 using intermediate 7b (70 mg, 258.95 μmol) and 4-(2-bromopyrimidine-4-yl)morpholine (75.85 mg, 310.74 μmol) as starting materials, and Example 46 (32.49 mg, 74.12 μmol, 28.62% yield) was obtained as a grayish-white solid.

[0364] 1 H-NMR (400 MHz, DMSO-d6) δ 8.35 (d, J=6.15 Hz, 1H), 7.77 (s, 1H), 7.15-7.21 (m, 1H), 6.96 (d, J=6.27 Hz, 1H), 6.89 (d, J=7.78 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 3.79 (s, 3H), 3.67 (br d, J=5.02 Hz, 4H), 3.62 (br d, J=4.77 Hz, 4H), 3.17 (br t, J=8.97 Hz, 1H), 2.62-2.83 (m, 3H), 2.52-2.59 (m, 1H), 2.18 (s, 3H), 1.93 (br s, 1H), 1.83 (dq, J=4.83, 11.90 Hz, 1H).

[0365] Example 47: 6-(5-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0366] Intermediate 6e: 3-Methoxy-5-(5-Methoxy-2-methylphenyl)-4,5,6,7-tetrahydroisobenzofuran-1(3H)-one Following Scheme 1, steps i to v, intermediate 6e was prepared using 2-bromo-4-methoxy-1-methylbenzene as the starting material, similar to intermediate 6a in Example 1, and was obtained as a yellow solid in a total yield of 9.3%.

[0367] 1 H NMR: (CDCl3, 400 MHz) δ 7.02 (d, J = 8.4 Hz, 1H), 6.70-6.61 (m, 2H), 5.58 (s, 1H), 3.71 (s, 3H), 3.51 (s, 3H), 3.05-2.90 (m, 1H), 2.47-2.36 (m, 2H), 2.31-2.14 (m, 5H), 1.94-1.86 (m, 1H), 1.75-1.62 (m, 1H)

[0368] Intermediate 7c: 6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 1, step vii, intermediate 7c was prepared using intermediate 6e (1.30 g, 4.51 mmol) as the starting material, similar to intermediate 7a in Example 6, and intermediate 7c (0.4 g, 1.48 mmol, 32.82% yield) was obtained as a white solid.

[0369] 1 H NMR: (CDCl3, 400 MHz) δ 7.55 (s, 1H), 7.09 (d, J = 8.0 Hz, 1H), 6.73-6.68 (m, 2H), 3.78 (s, 3H), 3.12-3.08 (m, 1H), 2.93-2.91 (m, 1H), 2.74-2.71 (m, 1H), 2.65-2.58 (m, 2H), 2.28 (s, 3H), 2.13-2.09 (m, 1H), 1.90-1.69 (m, 1H).

[0370] Example 47: 6-(5-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step viii, Example 47 was prepared according to Example 6 using intermediate 7c (0.1 g, 369.92 μmol) and 2-chloro-5-methylpyrimidine (142.67 mg, 1.11 mmol) as starting materials, and Example 47 (0.005 g, 13.80 μmol, 3.73% yield) was obtained as a yellow solid.

[0371] 1 H-NMR (400 MHz, CDCl3) δ 8.75 (s, 2H), 7.70 (s, 1H), 7.12 (br d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 6.72 (m, d, J = 8.4 Hz, 1H), 3.80 (s, 3H), 3.17-2.96 (m, 2H), 2.87-2.76 (m, 1H), 2.71-2.65 (m, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 2.15-2.11 (m, 1H), 1.90-1.85 (m,1H).

[0372] Example 48: 6-(5-methoxy-2-methylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0373] According to Scheme 1, step viii, Example 48 was prepared according to Example 6 using intermediate 7c (0.1 g, 369.92 μmol) and 2-chloro-5-methoxypyrimidine (160.43 mg, 1.11 mmol) as starting materials, and Example 48 (0.003 g, 7.93 μmol, 2.14% yield) was obtained as a white solid.

[0374] 1H-NMR (400 MHz, CDCl3) δ 8.46 (s, 2H), 7.59 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.73-6.64 (m, 2H), 3.93 (s, 3H), 3.73 (s, 3H), 3.04-2.97 (m, 2H), 2.71-2.46 (m, 3H), 2.23 (s, 3H), 2.08 (m, 1H), 1.80 (m, 1H).

[0375] Example 49: 2-(5-chloropyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0376] According to Scheme 1, step viii, Example 49 was prepared according to Example 6 using intermediate 7c (0.1 g, 369.92 μmol) and 2-bromo-5-chloropyrimidine (214.66 mg, 1.11 mmol) as starting materials, and Example 49 (0.011 g, 28.73 μmol, 7.77% yield) was obtained as a white solid.

[0377] 1 H-NMR (400 MHz, CDCl3) δ 8.85 (s, 2H), 7.69 (s, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H), 6.72 (dd, J = 8.0, 2.4 Hz, 1H), 3.80 (s, 3H), 3.18-3.08 (m, 1H), 3.07-2.97 (m, 1H), 2.86-2.76 (m, 1H), 2.71-2.65 (m, 2H), 2.31 (s, 3H), 2.15 (m, 1H), 1.88-1.81 (m, 1H).

[0378] Example 50: 6-(2,4-dimethylphenyl)-2-(pyridine-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0379] According to Scheme 1, step ix, a mixture of intermediate 7a (150.00 mg, 530.81 μmol, 1.00 eq) and 4-pyridylboronic acid (130.49 mg, 1.06 mmol, 2.00 eq) in dioxane (5.00 mL) was prepared, to which DMAP (194.55 mg, 1.59 mmol, 3.00 eq), pyridine (41.99 mg, 530.81 μmol, 42.84 μL, 1.00 eq), and Cu(OAc)2 (96.41 mg, 530.81 μmol, 1.00 eq) were added. This mixture was heated to 90°C and stirred for 12 hours. The reaction mixture was filtered, and the filtrate was acidified to pH=5 with 12 M HCl and filtered again. The obtained solution was purified by preparative HPLC to obtain Example 50 (8.98 mg, 26.01 μmol, 4.90% yield) as a yellow solid.

[0380] 1 H-NMR (400 MHz, DMSO-d6) δ 8.76 (br s, 2H), 7.97 (s, 1H), 7.78 (br s, 2H), 7.15 (d, J=8.5 Hz, 1H), 7.04 - 6.98 (m, 2H), 3.13 - 3.01 (m, 1H), 2.86 - 2.73 (m, 2H), 2.71 - 2.64 (m, 1H), 2.63 - 2.55 (m, 1H), 2.30 (s, 3H), 2.25 (s, 3H), 2.00 - 1.91 (m, 1H), 1.88 - 1.75 (m, 1H).

[0381] Example 51: 2-(5-chloropyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0382] Intermediate 6a': 5-formyl-2',4'-dimethyl-1,2,3,6-tetrahydro-[1,1'-biphenyl]-4-carboxylic acid To a solution of intermediate 6a (6 g, 22.03 mmol, 1 eq) in MeOH (100 mL), a solution of NaOH (2.64 g, 66.09 mmol, 3 eq) in H2O (40 mL) was added and the mixture was stirred at 20°C for 24 hours. The organic solvent was removed under reduced pressure. The residue was acidified to pH=3 by adding 2N HCl at 20°C and extracted with siRNA (30 mL x 3). The combined organic layers were washed with brine to pH=7, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE / siRNA = 50 / 1, 1 / 1) to obtain intermediate 6a' (2 g, 7.74 mmol, 35.14% yield) as a pale yellow oil.

[0383] 1 H NMR (400MHz, CDCl3) δ 7.16-6.93 (m, 3H), 6.03 (s, 1H), 3.20-3.01 (m, 1H), 2.79-2.64 (m, 1H), 2.56-2.42 (m, 2H), 2.36-2.31 (m, 7H), 2.04-1.96 (m, 1H), 1.90-1.73 (m, 1H).

[0384] Intermediate 8a: Ethyl 5-formyl-2',4'-dimethyl-1,2,3,6-tetrahydro-[1,1'-biphenyl]-4-carboxylate According to Scheme 1, step x, intermediate 6a' (2 g, 7.74 mmol, 1 eq) was dissolved in DMF (20 mL) and TMG (1.34 g, 11.61 mmol, 1.46 mL, 1.5 eq) was added at 20 °C. The mixture was then stirred at this temperature for 30 minutes. Ethyl iodide (3.02 g, 19.36 mmol, 1.55 mL, 2.5 eq) was added at 20 °C, and the resulting mixture was heated without delay at 45 °C for 14 hours. The solvent was removed under reduced pressure. The residue was dissolved in water (20 mL), the pH was adjusted to 4 with 4N HCl, and extracted with SiO2 (15 mL × 3). The combined organic layers were washed with water (10 mL × 2), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE / SiO7 = 20 / 1, 1 / 1) to obtain intermediate 8a (1.8 g, 6.29 mmol, 81.18% yield) as a yellow oily substance.

[0385] 1 H NMR (400MHz, CDCl3) δ10.08(s, 1H), 7.13-6.94(m, 3H), 4.34(q, J = 7.2 Hz, 2H), 3.00-2.88(m, 1H), 2.83-2.71(m, 2H), 2.70-2.57(m, 1H), 2.31(s, 6H), 2.25-2.13(m, 1H), 1.99(m, 1H), 1.87-1.72(m, 1H), 1.38(t, J = 7.2 Hz, 3H).

[0386] Example 51: (2-(5-chloropyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step xii, 2-hydrazinyl-5-chloropyrimidine (105.15 mg, 367.19 μmol, 1 eq) was added all at once to a mixture of intermediate 8a (53.08 mg, 367.19 μmol, 1 eq) in EtOH (10 mL) and AcOH (5 mL) at 20°C. The mixture was stirred at 100°C for 12 hours. The mixture was filtered and concentrated under vacuum. The residue was purified by preparative HPLC to obtain Example 51 (0.009 g, 24.53 μmol, 6.68% yield) as a white solid.

[0387] 1 H-NMR (400 MHz, CDCl3) δ 8.86 (s, 2H), 7.69 (s, 1H), 7.16 - 6.99 (m, 3H), 3.14 (m, 1H), 3.01 (m, 1H), 2.86 - 2.77 (m, 1H), 2.75 - 2.60 (m, 2H), 2.35 (s, 3H), 2.33 (s, 3H), 2.12 (m, 1H), 1.93 - 1.82 (m, 1H).

[0388] Example 52: 6-(2,4-dimethylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0389] According to Scheme 1, step xii, Example 52 was prepared according to Example 51, using intermediate 8a (105.15 mg, 367.19 μmol) and 2-hydrazinyl-5-methylpyrimidine (45.58 mg, 367.19 μmol) as starting materials, and Example 52 (0.023 g, 66.39 μmol, 18.08% yield) was obtained as a white solid.

[0390] 1 H-NMR (400 MHz, CDCl3) δ 8.74 (s, 2H), 7.68 (s, 1H), 7.16-6.99 (m, 3H), 3.14 (m, 1H), 3.06-2.96 (m, 1H), 2.86-2.76 (m, 1H), 2.69 (m, 2H), 2.43 (s, 3H), 2.36 (s, 3H), 2.32 (s, 3H), 2.16-2.08 (m, 1H), 1.93-1.81 (m, 1H).

[0391] Example 53: 6-(2,4-dimethylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0392] According to Scheme 1, step xii, Example 53 was prepared according to Example 51 using intermediate 8a (105.15 mg, 367.19 μmol) and 2-hydrazinyl-5-methoxypyrimidine (51.46 mg, 367.19 μmol) as starting materials, and Example 53 (0.059 g, 161.16 μmol, 43.89% yield) was obtained as a white solid.

[0393] 1 H-NMR (400 MHz, CDCl3) δ 8.53 (s, 2H), 7.67 (s, 1H), 7.15 - 6.97 (m, 3H), 4.00 (s, 3H), 3.14 (br s, 1H), 2.99 (m, 1H), 2.85 - 2.76 (m, 1H), 2.74-2.59 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.12 (m, 1H), 1.87 (m, 1H).

[0394] Example 54: 6-(2,4-dimethylphenyl)-2-(5-fluoropyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0395] According to Scheme 1, step xii, Example 54 was prepared according to Example 51 using intermediate 8a (105.15 mg, 367.19 μmol) and 5-fluoro-2-hydrazinylpyrimidine (47.04 mg, 367.19 μmol) as starting materials, and Example 54 (0.077 g, 217.32 μmol, 59.18% yield) was obtained as a white solid.

[0396] 1 H-NMR (400 MHz, CDCl3) δ 8.77 (s, 2H), 7.68 (s, 1H), 7.13-6.99 (m, 3H), 3.15 (m, 1H), 3.00 (m, 1H), 2.87-2.77 (m, 1H), 2.70 (m, 2H), 2.36 (s, 3H), 2.32 (s, 3H), 2.15-2.08 (m, 1H), 1.95-1.82 (m, 1H).

[0397] Example 55: 6-(2,4-dimethylphenyl)-2-(5-(trifluoromethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0398] According to Scheme 1, step xii, Example 55 was prepared according to Example 51 using intermediate 8a (105.15 mg, 367.19 μmol) and 2-hydrazinyl-5-(trifluoromethyl)pyrimidine (65.40 mg, 367.19 μmol) as starting materials, and Example 55 (0.023 g, 55.36 μmol, 15.08% yield) was obtained as a white solid.

[0399] 1H-NMR (400 MHz, CDCl3) δ 9.08 (s, 2H), 7.65 (s, 1H), 7.08-6.96 (m, 3H), 3.21-3.10 (m, 1H), 3.07-2.97 (m, 1H), 2.87- 2.78 (m, 1H), 2.36 (s, 3H), 2.33 (s, 3H), 2.14 (m, 1H), 1.95 - 1.83 (m, 1H).

[0400] Example 56: 6-(2,4-dimethylphenyl)-2-(4-methoxy-5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0401] Intermediate 56': 2-(5-bromo-4-methoxypyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step xii, intermediate 56' was prepared according to Example 51, using intermediate 8a (392.32 mg, 1.37 mmol) and 5-bromo-2-hydrazinyl-4-methoxypyrimidine (0.3 g, 1.37 mmol) as starting materials, and intermediate 56' (0.17 g, 385.21 μmol, 28.12% yield) was obtained as a white solid.

[0402] 1 H NMR (400MHz, CDCl3) δ 8.71 (s, 1H), 7.66 (s, 1H), 7.14-6.99 (m, 3H), 4.13 (s, 3H), 3.20-3.08 (m, 1H), 3.04-2.94 (m, 1H), 2.85-2.75 (m, 1H), 2.75-2.65 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.19-2.09 (m, 1H), 1.92-1.85 (m,1H).

[0403] Example 56: 6-(2,4-dimethylphenyl)-2-(4-methoxy-5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one To a mixture of methylboronic acid (27.13 mg, 453.19 μmol) and intermediate 56' (0.1 g, 226.59 μmol) in dioxane (10 mL), Pd(dppf)Cl2 (16.58 mg, 22.66 μmol, 0.1 eq) and K2CO3 (93.95 mg, 679.78 μmol, 3 eq) were added all at once at 20 °C under N2. This mixture was stirred at 100 °C for 12 hours. This mixture was filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to obtain Example 56 (0.044 g, 116.27 μmol, 51.31% yield) as a white solid.

[0404] 1 H-NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.66 (s, 1H), 7.14-6.99 (m, 3H), 4.13 (s, 3H), 3.20-3.08 (m, 1H), 3.04-2.94 (m, 1H), 2.85-2.75 (m, 1H), 2.75-2.65 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.19-2.09 (m, 1H), 1.92-1.85 (m,1H).

[0405] Example 57: 6-(2,4-dimethylphenyl)-2-(5-(morpholinomethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method C. [ka]

[0406] According to Scheme 1, step xii, Example 57 was prepared according to Example 51 using intermediate 8a (105.15 mg, 367.19 μmol) and 4-((2-hydrazinylpyrimidine-5-yl)methyl)morpholine (76.83 mg, 367.19 μmol) as starting materials, and Example 57 (0.023 g, 53.30 μmol, 14.52% yield) was obtained as a white solid.

[0407] 1 H-NMR (400 MHz, CDCl3) δ 8.87 (s, 2H), 7.69 (s, 1H), 7.17-6.98 (m, 3H), 3.78-3.70 (m, 4H), 3.60 (s, 2H), 3.15 (m, 1H), 3.01 (m, 1H), 2.87-2.76 (m, 1H), 2.70 (m, 1H), 2.75 - 2.61 (m, 1H), 2.51 (m, 4H), 2.36 (s, 3H), 2.32 (s, 3H), 2.11 (m, 1H), 1.95-1.81 (m, 1H).

[0408] Example 58: 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0409] Intermediate 10: 8-chloro-1,4-dioxaspiro[4.5]deca-7-ene-7-carbaldehyde According to Scheme 2, step i, a solution of DMF (187.11 g, 2.56 mol, 196.96 mL, 2.00 eq) in CH2Cl2 (2.00 L) is prepared at 0°C using POCl 3(490.66 g, 3.20 mol, 297.37 mL, 2.50 eq) was added dropwise. The mixture was stirred at 0°C for 2 hours. Next, a solution of 1,4-dioxaspiro[4.5]decan-8-one (200.00 g, 1.28 mol, 1.00 eq) in CH2Cl2 (500.00 mL) was added dropwise to the mixture at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was poured into a saturated aqueous solution of NaHCO3 (2 L), solid NaHCO3 was added to maintain pH > 7, and the mixture was extracted with CH2Cl2 (5 L × 2) to concentrate the CH2Cl2 phase. The resulting residue was purified by column chromatography (PE / siRNA = 20 / 1). Intermediate 56a (120.00 g, 506.34 mmol, 39.56% yield) was obtained as a yellow oil.

[0410] 1 H NMR (400MHz, CDCl3) δ 10.19 - 10.10 (m, 1H), 4.05 - 3.94 (m, 4H), 2.91 - 2.75 (m, 2H), 2.57 - 2.42 (m, 2H), 1.99 - 1.83 (m, 2H).

[0411] Intermediate 11: Methyl 7-formyl-1,4-dioxaspiro[4.5]deca-7-ene-8-carboxylate Following Scheme 2, step ii, intermediate 10 (122.00 g, 514.78 mmol, 1.00 eq) was dissolved in MeOH (800.00 mL) and DMA (400.00 mL) and Pd(OAc)2 (17.34 g, 77.22 mmol, 0.15 eq), DPPF (42.81 g, 77.22 mmol, 0.15 eq), and AcONa (84.45 g, 1.03 mol, 2.00 eq) were added. The reaction mixture was stirred at 80°C for 12 hours under CO (50 psi). The reaction mixture was filtered, the filtrate was concentrated, and the residue was poured into water (2000 mL x 2) and extracted with ethyl acetate (2000 mL x 3). The combined organic layers were washed with saturated brine (1000 ml x 3) and concentrated under reduced pressure. The residue was purified by column chromatography (PE:SiO = 20:1 to 3:1). Intermediate 11 (78.50 g, 329.64 mmol, 64.04% yield) was obtained as a yellow oily substance.

[0412] 1 H NMR (400MHz, CDCl3) δ 5.61 (d, J=1.1 Hz, 1H), 4.03 - 3.99 (m, 4H), 3.53 (s, 3H), 2.62 - 2.53 (m, 1H), 2.49 - 2.40 (m, 3H), 1.85 (t, J=6.3 Hz, 2H).

[0413] Intermediate 12: 7,8-dihydro-2H-spiro[phthalazine e-6,2'-[1,3]dioxolane]-1(5H)-one Following Scheme 2, step iii, intermediate 11 (78.50 g, 329.64 mmol, 1.00 eq) was dissolved in EtOH (750.00 mL) and AcOH (75.00 mL), to which N2H4.H2O (33.68 g, 659.28 mmol, 32.70 mL, 2.00 eq) was added. This mixture was stirred at 80°C for 12 hours. The reaction mixture was concentrated and adjusted to pH=7 with saturated NaHCO3 aqueous solution. It was then extracted with CH2Cl2 (30.00 mL × 3). The combined organic layer was dried over Na2SO4, filtered, and concentrated. Intermediate 12 (66.00 g, 316.99 mmol, 96.16% yield) was obtained as a yellow solid.

[0414] 1 H NMR (400MHz, DMSO-d6) δ 7.58 (s, 1H), 3.93 (s, 4H), 2.72 (s, 2H), 2.54 (br t, J=6.7 Hz, 2H), 1.80 (t, J=6.7 Hz, 2H).

[0415] Intermediate 13a: 2-(pyridine-2-yl)-7,8-dihydro-2H-spiro[phthalazine-6,2'-[1,3]dioxolane]-1(5H)-one According to Scheme 2, step v, intermediate 12 (40.00 g, 192.11 mmol, 1.00 eq) and 2-bromopyridine (36.42 g, 230.53 mmol, 21.94 mL, 1.20 eq) are dissolved in dioxane (500.00 mL) and CuI (7.32 g, 38.42 mmol, 0.20 eq), (1S,2S)-N 1 ,N 2- Dimethylcyclohexane-1,2-diamine (5.47 g, 38.42 mmol, 0.20 eq) and K3PO4 (101.95 g, 480.28 mmol, 2.50 eq) were added. The mixture was stirred at 100°C for 12 hours. The reaction product was filtered and concentrated. The filtered cake was washed with CH2Cl2 (200 mL x 3). Water (2.0 L) was added to the residue and extracted with CH2Cl2 (1.0 L x 3). The combined organic layer was dried over Na2SO4, filtered, and concentrated. The residue was recrystallized from MTBE (100 mL) at 20°C. Intermediate 13a (56.00 g, crude) was obtained as a gray solid.

[0416] 1 H NMR (400MHz, CDCl3) δ 8.67 (br s, 1H), 7.92 - 7.79 (m, 1H), 7.68 (br s, 2H), 7.35 (br s, 1H), 4.04 (s, 4H), 2.87 (br t, J=6.0 Hz, 2H), 2.81 (s, 2H), 1.94 (br t, J=6.5 Hz, 2H).

[0417] Intermediate 14a: 2-(pyridine-2-yl)-7,8-dihydrophthalazine-1,6(2H,5H)-dione Following Scheme 2, step vi, intermediate 13a (25.00 g, 87.63 mmol, 1.00 eq) was dissolved in CH2Cl2 (250.00 mL) and TFA (75.00 mL), to which H2O (3.16 g, 175.26 mmol, 3.16 mL, 2.00 eq) was added. This mixture was stirred at 20°C for 12 hours. The reaction product was poured into saturated NaHCO3 aqueous solution (500.0 mL) and extracted with CH2Cl2 (500.0 mL × 3). The combined organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (SiO2, CH2Cl2:siRNA = 1:2~0:1). Intermediate 14a (8.80 g, 33.20 mmol, 37.88% yield) was obtained as a yellow solid.

[0418] 1 H NMR (400MHz, CDCl3) δ 8.67 (dd, J=1.1, 4.9 Hz, 1H), 7.89 (dt, J=1.9, 7.7 Hz, 1H), 7.75 (s, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.39 (ddd, J=0.9, 4.9, 7.4 Hz, 1H), 3.46 (s, 2H), 3.16 (t, J=7.0 Hz, 2H), 2.67 (t, J=7.0 Hz, 2H).

[0419] Intermediate 15a: 1-Oxo-2-(pyridine-2-yl)-1,2,7,8-tetrahydrophthalazine-6-yltrifluoromethane-sulfonate Following Scheme 2, step vii, Et3N (2.29 g, 22.63 mmol, 3.14 mL, 1.20 eq) and Tf2O (5.85 g, 20.75 mmol, 3.42 mL, 1.10 eq) were added to a solution of intermediate 14a (5.00 g, 18.86 mmol, 1.00 eq) in CH2Cl2 (50.00 mL) at 0°C. The reaction mixture was stirred at 20°C for 12 hours. The reaction mixture was concentrated to obtain the residue. This residue was purified by column chromatography (SiO2, PE:siRNA = 5:1 to 1:1). Intermediate 15a (4.40 g, 11.43 mmol, 60.62% yield) was obtained as a yellow solid.

[0420] 1 H NMR (400MHz, CDCl3) δ 8.68 - 8.63 (m, 1H), 7.88 (dt, J=1.9, 7.8 Hz, 1H), 7.78 (s, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.38 (ddd, J=0.9, 4.9, 7.4 Hz, 1H), 6.36 (t, J=1.4 Hz, 1H), 3.18 - 3.10 (m, 2H), 2.84 - 2.75 (m, 2H).

[0421] Intermediate 16a: 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one Following Scheme 2, step viiii, a mixture of intermediate 15a (200.00 mg, 518.07 μmol, 1.00 eq), (2-methoxyphenyl)-boronic acid (157.45 mg, 1.04 mmol, 2.00 eq), Pd(PPh3)4 (119.73 mg, 103.61 μmol, 0.20 eq), and Na2CO3 (2 M, 1.17 mL, 4.50 eq) in THF (4.00 mL) was degassed, purged with N2 for 3 hours, and then stirred under an N2 atmosphere at 70°C for 3 hours. Water (20 mL) was added to this mixture, extracted with AcOEt (20 mL × 3), the organic layer was dried with Na2SO4, filtered, concentrated under reduced pressure to obtain the residue. This residue was purified by preparative TLC (PE:SiO=0:1) to obtain intermediate 16a (190.00 mg, crude) as a yellow oily substance.

[0422] Example 58: 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, a mixture of intermediate 16a (200.00 mg, 283.67 μmol, 1.00 eq), Pd(OH)2 (79.68 mg, 56.73 μmol, 10% purity, 0.20 eq), and ammonium formate (178.88 mg, 2.84 mmol, 10.00 eq) in EtOH (20.00 mL) was degassed, purged with N2 for 3 hours, and then stirred under an N2 atmosphere at 60°C for 2 hours. This mixture was filtered, concentrated under reduced pressure, and purified by preparative HPLC to obtain Example 58 (27.59 mg, 82.68 μmol, 29.15% yield) as a white solid.

[0423] 1 H-NMR (400 MHz, CDCl3) δ 8.68 (dd, J=1.1, 4.8 Hz, 1H), 7.88 (dt, J=1.9, 7.8 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.37 (ddd, J=0.9, 4.9, 7.3 Hz, 1H), 7.28 - 7.25 (m, 1H), 7.21 (dd, J=1.5, 7.5 Hz, 1H), 7.02 - 6.97 (m, 1H), 6.94 (d, J=8.3 Hz, 1H), 3.88 (s, 3H), 3.45 - 3.31 (m, 1H), 3.05 - 2.88 (m, 2H), 2.75 - 2.60 (m, 2H), 2.22 - 2.13 (m, 1H), 2.05 - 1.89 (m, 1H).

[0424] Example 59: 6-(3-(dimethylamino)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0425] Intermediate 16b: 6-(3-(dimethylamino)phenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16b was prepared using intermediate 15a (200.00 mg, 486.46 μmol) and (3-(dimethylamino)phenyl)boronic acid (160.53 mg, 972.92 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16b (160.00 mg, 427.40 μmol, 87.86% yield) was obtained as a yellow oily substance.

[0426] Example 59: 6-(3-(dimethylamino)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 59 was prepared using intermediate 16b (160.00 mg, 427.40 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 59 (15.47 mg, 43.85 μmol, 10.26% yield) was obtained as a white solid.

[0427] 1 H-NMR (400 MHz, CDCl3) δ 8.69 (dd, J=1.1, 4.8 Hz, 1H), 7.89 (dt, J=1.9, 7.8 Hz, 1H), 7.78 - 7.73 (m, 2H), 7.38 (ddd, J=1.0, 4.9, 7.4 Hz, 1H), 7.26 (t, J=8.1 Hz, 1H), 6.70 - 6.63 (m, 3H), 3.05 - 2.98 (m, 1H), 3.05 - 2.98 (m, 7H), 2.96 - 2.86 (m, 2H), 2.84 - 2.75 (m, 1H), 2.72 - 2.59 (m, 1H), 2.30 - 2.21 (m, 1H), 1.98 - 1.85 (m, 1H).

[0428] Example 60: 6-(3-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0429] Intermediate 16c: 6-(3-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16c was prepared using intermediate 15a (200.00 mg, 518.07 μmol) and (3-methoxy-2-methylphenyl)boronic acid (85.99 mg, 518.07 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16c (200.00 mg, 272.16 μmol, 52.53% yield) was obtained as a yellow oily substance.

[0430] Example 60: 6-(3-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 60 was prepared using intermediate 16c (170.00 mg, 492.20 μmol) as a starting material, following the same method as described, for example, in 58, and Example 60 (24.35 mg, 69.95 μmol, 14.21% yield) was obtained as a white solid.

[0431] 1H-NMR (400 MHz, CDCl3) δ 8.69 (dd, J=1.1, 4.8 Hz, 1H), 7.89 (dt, J=1.9, 7.8 Hz, 1H), 7.79 - 7.71 (m, 2H), 7.38 (ddd, J=0.9, 4.9, 7.4 Hz, 1H), 7.26 - 7.18 (m, 1H), 6.91 - 6.78 (m, 2H), 3.87 (s, 3H), 3.31 - 3.18 (m, 1H), 3.06 - 2.94 (m, 1H), 2.89 - 2.79 (m, 1H), 2.78 - 2.63 (m, 2H), 2.27 (s, 3H), 2.20 - 2.12 (m, 1H), 1.98 - 1.85 (m, 1H).

[0432] Example 61: 6-(5-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0433] Intermediate 16d: 6-(5-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16d was prepared using intermediate 15a (227.51 mg, 589.32 μmol) and (5-methoxy-2-methylphenyl)boronic acid (97.82 mg, 589.32 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16d (200.00 mg, crude) was obtained as a yellow oily substance.

[0434] Example 61: 6-(5-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 61 was prepared using intermediate 16d (200.00 mg, 579.06 μmol) as a starting material, following the same method as described, for example, in 58, and Example 61 (19.01 mg, 52.64 μmol, 9.09% yield) was obtained as a white solid.

[0435] 1 H-NMR (400 MHz, CDCl3) δ 8.69 (dd, J=1.1, 4.8 Hz, 1H), 7.89 (dt, J=1.9, 7.8 Hz, 1H), 7.77 - 7.73 (m, 2H), 7.38 (ddd, J=1.0, 4.9, 7.4 Hz, 1H), 7.15 (d, J=8.3 Hz, 1H), 6.80 (d, J=2.6 Hz, 1H), 6.74 (dd, J=2.6, 8.3 Hz, 1H), 3.82 (s, 3H), 3.20 - 3.10 (m, 1H), 3.08 - 2.99 (m, 1H), 2.88 - 2.80 (m, 1H), 2.75 - 2.62 (m, 2H), 2.33 (s, 3H), 2.22 - 2.13 (m, 1H), 1.95 - 1.83 (m, 1H).

[0436] Example 62: 2-(pyridine-2-yl)-6-(o-tolyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0437] Intermediate 16e: 2-(pyridine-2-yl)-6-(o-tolyl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16e was prepared using intermediate 15a (200.00 mg, 486.46 μmol) and o-trilboronic acid (132.28 mg, 972.92 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16e (70.00 mg, 210.86 μmol, 43.35% yield) was obtained as a brown solid.

[0438] Example 62: 2-(pyridine-2-yl)-6-(o-tolyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 62 was prepared using intermediate 16e (70.00 mg, 210.86 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 62 (12.55 mg, 39.07 μmol, 18.53% yield) was obtained as a white solid.

[0439] 1 H-NMR (400 MHz, CDCl3) δ 8.59 (dd, J=1.1, 4.8 Hz, 1H), 7.80 (dt, J=1.9, 7.7 Hz, 1H), 7.70 - 7.62 (m, 2H), 7.29 (ddd, J=0.9, 4.9, 7.5 Hz, 1H), 7.17 - 7.07 (m, 4H), 3.16 - 3.05 (m, 1H), 2.98 - 2.86 (m, 1H), 2.81 - 2.71 (m, 1H), 2.69 - 2.53 (m, 2H), 2.32 (s, 3H), 2.13 - 2.03 (m, 1H), 1.89 - 1.76 (m, 1H).

[0440] Example 63: 6-(3-cyclopropylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0441] Intermediate 16f: 6-(3-cyclopropylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16f was prepared using intermediate 15a (100.00 mg, 243.23 μmol) and (3-cyclopropylphenyl)boronic acid pinacol ester (89.07 mg, 364.85 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16f (20.00 mg, 42.76 μmol, 17.58% yield) was obtained as a brown solid.

[0442] Example 63: 6-(3-cyclopropylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 63 was prepared using intermediate 16f (10.00 mg, 21.38 μmol) as the starting material, following the same method as described, for example, in 58, and Example 63 (4.63 mg, 13.48 μmol, 63.06% yield) was obtained as a white solid.

[0443] 1 H-NMR (400 MHz, CDCl3) δ 8.68 (br d, J=3.8 Hz, 1H), 7.94 - 7.84 (m, 1H), 7.79 - 7.71 (m, 2H), 7.42 - 7.34 (m, 1H), 7.31 - 7.23 (m, 2H), 7.09 - 7.01 (m, 2H), 6.97 (br d, J=7.4 Hz, 1H), 3.05 - 2.84 (m, 3H), 2.82 - 2.60 (m, 2H), 2.24 (br d, J=8.9 Hz, 1H), 1.98 - 1.83 (m, 2H), 1.06 - 0.95 (m, 2H), 0.74 (q, J=4.9 Hz, 2H).

[0444] Example 64: 6-(3-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0445] Intermediate 16g: 6-(3-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, 16 g of intermediate was prepared using intermediate 15a (200.00 mg, 518.07 μmol) and (3-methoxy-4-methylphenyl)boronic acid (171.98 mg, 1.04 mmol) as starting materials, according to the method described for intermediate 16a in Example 58, and 16 g of intermediate (130.00 mg, 299.60 μmol, 57.83% yield) was obtained as a yellow solid. m / z(M+H) + = 346.1.

[0446] Example 64: 6-(3-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 64 was prepared using 16 g (130.00 mg, 299.60 μmol) of the intermediate as a starting material, in the same manner as described, for example, in 58, and Example 64 (31.00 mg, 89.23 μmol, 29.78% yield) was obtained as a white solid.

[0447] 1 H-NMR (400 MHz, CDCl3) δ 8.62 - 8.56 (m, 1H), 7.83 - 7.76 (m, 1H), 7.68 - 7.62 (m, 2H), 7.32 - 7.25 (m, 1H), 7.04 (d, J=7.5 Hz, 1H), 6.69 (d, J=7.5 Hz, 1H), 6.66 (s, 1H), 3.79 (s, 3H), 2.96 - 2.76 (m, 3H), 2.74 - 2.49 (m, 2H), 2.21 - 2.10 (m, 4H), 1.88 - 1.73 (m, 1H).

[0448] Example 65: 6-(3-(1-hydroxyethyl)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0449] Intermediate 16h: 6-(3-acetylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16h was prepared using intermediate 15a (100.00 mg, 243.23 μmol) and (3-acetylphenyl)boronic acid (59.82 mg, 364.85 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16h (70.00 mg, 156.97 μmol, 64.54% yield) was obtained as a grayish-white solid. m / z(M+H) + = 344.1.

[0450] Example 65: 6-(3-(1-hydroxyethyl)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 65 was prepared using intermediate 16h (70.00 mg, 156.97 μmol) as the starting material, following the same method as described, for example, in 58, and Example 65 (4.05 mg, 11.54 μmol, 4.31% yield) was obtained as a white solid.

[0451] 1H-NMR (400 MHz, CDCl3) δ 8.68 (br d, J=3.9 Hz, 1H), 7.93 - 7.85 (m, 1H), 7.79 - 7.70 (m, 2H), 7.41 - 7.35 (m, 2H), 7.32 (br d, J=7.9 Hz, 2H), 7.21 (br d, J=7.5 Hz, 1H), 4.95 (q, J=6.3 Hz, 1H), 3.06 - 2.96 (m, 2H), 2.95 - 2.86 (m, 1H), 2.84 - 2.74 (m, 1H), 2.73 - 2.61 (m, 1H), 2.26 (br d, J=9.0 Hz, 1H), 1.98 - 1.88 (m, 1H), 1.88 - 1.77 (m, 1H), 1.55 (d, J=6.5 Hz, 3H).

[0452] Example 66: 6-(3-cyclopropoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0453] Intermediate 16i: 6-(3-cyclopropoxyphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16i was prepared using intermediate 15a (100.00 mg, 243.23 μmol) and (3-cyclopropoxyphenyl)boronic acid pinacol ester (96.85 mg, 364.84 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16i (80.00 mg, 118.63 μmol, 48.78% yield) was obtained as a grayish-white solid. m / z(M+H) + = 358.1.

[0454] Example 66: 6-(3-cyclopropoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 66 was prepared using intermediate 16i (40.00 mg, 59.32 μmol) as the starting material, following the same method as described, for example, in 58, and Example 66 (8.54 mg, 23.74 μmol, 40.01% yield) was obtained as a white solid.

[0455] 1 H-NMR (400 MHz, CDCl3) δ 8.68 (br d, J=4.3 Hz, 1H), 7.89 (dt, J=1.6, 7.7 Hz, 1H), 7.78 - 7.72 (m, 2H), 7.38 (dd, J=5.0, 7.2 Hz, 1H), 7.34 - 7.29 (m, 1H), 7.01 (dd, J=2.0, 8.2 Hz, 1H), 6.94 (s, 1H), 6.90 (d, J=7.7 Hz, 1H), 3.82 - 3.71 (m, 1H), 3.03 - 2.86 (m, 3H), 2.82 - 2.59 (m, 2H), 2.25 (br d, J=13.2 Hz, 1H), 1.97 - 1.83 (m, 1H), 0.84 - 0.79 (m, 4H).

[0456] Example 67: 6-(2-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0457] Intermediate 16j: 6-(2-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16j was prepared using intermediate 15a (200.00 mg, 519.68 μmol) and (2-methoxy-4-methylphenyl)boronic acid (129.38 mg, 779.52 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16j (180.00 mg, crude) was obtained as a brown oily substance. m / z(M+H) + = 346.1.

[0458] Example 67: 6-(2-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 67 was prepared using intermediate 16j (180.00 mg, 521.15 μmol) as the starting material, following the same method as described, for example, in 58, and Example 67 (24.94 mg, 71.64 μmol, 13.75% yield) was obtained as a white solid.

[0459] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.9 Hz, 1H), 7.08 (dt, J=1.4, 8.0 Hz, 1H), 6.93 - 6.87 (m, 1H), 6.81 (t, J=6.5 Hz, 1H), 3.92 (s, 3H), 3.41 - 3.28 (m, 1H), 3.04 - 2.88 (m, 2H), 2.81 - 2.63 (m, 2H), 2.24 - 2.14 (m, 1H), 2.02 - 1.91 (m, 1H).

[0460] Example 68: 6-(2-methoxy-3-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0461] Intermediate 16k: 6-(2-methoxy-3-methylphenyl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16k was prepared using intermediate 15a (200.00 mg, 519.68 μmol) and (2-methoxy-3-methylphenyl)boronic acid pinacol ester (214.90 mg, 779.51 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16k (190.00 mg, crude) was obtained as a brown oily substance. m / z(M+H) + = 346.1.

[0462] Example 68: 6-(2-methoxy-3-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 68 was prepared using intermediate 16k (190.00 mg, 550.10 μmol) as the starting material, following the same method as described in, for example, 58, and Example 68 (16.44 mg, 46.80 μmol, 8.51% yield) was obtained as a white solid.

[0463] 1 H-NMR (400 MHz, DMSO-d6) δ 8.43 (s, 2H), 7.79 (s, 1H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.78 Hz, 1H), 6.85 (d, J=8.28 Hz, 1H), 3.76-3.81 (m, 3H), 3.11-3.25 (m, 1H), 2.67-2.84 (m, 3H), 2.55-2.60 (m, 1H), 2.18 (s, 3H), 1.93 (br s, 1H), 1.76-1.89 (m, 1H).

[0464] Example 69: 6-(1-methylindolin-4-yl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0465] Intermediate 16L: 6-(1-methylindoline-4-yl)-2-(pyridine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16l was prepared using intermediate 15a (0.2 g, 535.75 μmol) and (1-methylindoline-4-yl)boronic acid pinacol ester (138.84 mg, 535.75 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16l (0.15 g, crude) was obtained as a yellow solid. m / z(M+H) + = 357.3

[0466] 1 H NMR (MeOD, 400 MHz) δ 8.60 (br d, J = 4.4 Hz, 1H), 7.94-8.08 (m, 2H), 7.67 (br d, J = 7.6 Hz, 1H), 7.46-7.56 (m, 1H), 7.13 (br t, J = 7.6 Hz, 1H), 6.77 (br d, J = 8.0 Hz, 1H), 6.47-6.59 (m, 2H), 3.04-3.14 (m, 2H), 2.87-2.97 (m, 2H), 2.79-2.86 (m, 2H), 2.76 (s, 3H).

[0467] Example 69: 6-(1-methylindolin-4-yl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 69 was prepared using 16 liters of intermediate (0.15 g, 420.85 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 69 (55 mg, 151.30 μmol, 35.95% yield) was obtained as a white solid.

[0468] 1H-NMR (400 MHz, DMSO-d6) δ 8.67 (br d, J = 3.6 Hz, 1H), 7.87 (td, J = 7.8, 2.0 Hz, 1H), 7.71-7.78 (m, 2H), 7.36 (dd, J = 6.4, 5.0 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 6.58 (d, J = 7.8 Hz, 1H), 6.42 (d, J = 7.8 Hz, 1H), 3.29-3.41 (m, 2H), 2.89-3.11 (m, 4H), 2.75-2.88 (m, 5H), 2.53-2.72 (m, 1H), 2.17 (m, 1H), 1.80-1.98 (m, 1H).

[0469] Example 70: 6-(2-methoxy-4-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0470] Intermediate 13b: 2-(pyrimidine-2-yl)-7,8-dihydro-2H-spiro[phthalazine-6,2'-[1,3]dioxolane]-1(5H)-one According to Scheme 2, step iv, intermediate 13b was prepared using intermediate 12 (40.00 g, 192.11 mmol) and 2-bromopyrimidine (36.65 g, 230.53 mmol) as starting materials, according to the method described for intermediate 13a, and intermediate 13b (62.00 g, crude) was obtained as a gray solid.

[0471] 1 H NMR (400MHz, CDCl3) δ 8.92 (d, J=4.8 Hz, 2H), 7.63 (s, 1H), 7.40 (t, J=4.8 Hz, 1H), 4.05 (s, 4H), 2.91 (br t, J=6.7 Hz, 2H), 2.81 (s, 2H), 1.94 (t, J=6.7 Hz, 2H).

[0472] Intermediate 14b: 2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1,6(2H,5H)-dione Following Scheme 2, step vi, intermediate 14b was prepared using intermediate 13b (18.00 g, 62.87 mmol) as the starting material, in the same manner as described for intermediate 14a, and intermediate 14b (7.60 g, 18.83 mmol, 29.95% yield) was obtained as a brown solid.

[0473] 1 H NMR (400MHz, DMSO-d6) δ 9.04 (d, J=4.8 Hz, 2H), 7.88 (s, 1H), 7.79 (d, J=6.4 Hz, 1H), 3.55 (s, 2H), 2.95 (br t, J=6.9 Hz, 2H), 2.56 (t, J=7.0 Hz, 2H).

[0474] Intermediate 15b: 1-Oxo-2-(pyrimidine-2-yl)-1,2,7,8-tetrahydrophthalazine-6-yltrifluoromethane-sulfonate Following Scheme 2, step vii, intermediate 15b was prepared using intermediate 14b (3.50 g, 14.45 mmol) as the starting material, according to the method described for intermediate 15a, and intermediate 15b (4.30 g, 8.62 mmol, 59.63% yield) was obtained as a yellow solid.

[0475] 1 H NMR (400MHz, MeOD) δ 9.03 - 8.94 (m, 2H), 8.03 - 7.92 (m, 1H), 7.70 - 7.59 (m, 1H), 6.66 (t, J=1.4 Hz, 1H), 3.15 - 3.05 (m, 2H), 2.92 - 2.83 (m, 2H).

[0476] Intermediate 16m: 6-(2-methoxy-4-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16m was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (2-methoxy-4-methylphenyl)boronic acid (119.73 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16m (177.00 mg, crude) was obtained as a yellow oily substance. m / z(M+H) + = 347.1.

[0477] Example 70: 6-(2-methoxy-4-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 70 was prepared using intermediate 16m (177.00 mg, 511.00 μmol) as the starting material, following the same method as described, for example, in 58, and Example 70 (23.80 mg, 62.85 μmol, 12.30% yield) was obtained as a white solid.

[0478] 1 H-NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 9.02 (s, 1H), 7.85 (s, 1H), 7.72 (t, J=4.89 Hz, 1H), 7.12-7.18 (m, 1H), 6.88 (d, J=3.39 Hz, 1H), 6.86 (d, J=3.89 Hz, 1H), 4.43-4.71 (m, 1H), 3.12-3.22 (m, 1H), 2.66-2.86 (m, 3H), 2.56 (br d, J=9.91 Hz, 1H), 2.18 (s, 3H), 1.91-2.00 (m, 1H), 1.79-1.90 (m, 1H), 1.28 (d, J=6.02 Hz, 6H).

[0479] Example 71: 6-(2-methoxy-3-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0480] Intermediate 16n: 6-(2-methoxy-3-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16n was prepared using intermediate 15b (200.00 mg, 480.90 μmol) and (2-methoxy-3-methylphenyl)boronic acid pinacol ester (198.88 mg, 721.35 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16n (180.00 mg, crude) was obtained as a brown oily substance. m / z(M+H) + = 347.1.

[0481] Example 71: 6-(2-methoxy-3-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 71 was prepared using intermediate 16n (180.00 mg, 519.66 μmol) as the starting material, following the same method as described, for example, in 58, and Example 71 (13.00 mg, 37.31 μmol, 7.18% yield) was obtained as a white solid.

[0482] 1 H-NMR (400 MHz, CDCl3) δ 9.04 (s, 1H), 9.02 (s, 1H), 7.86 (s, 1H), 7.72 (t, J=4.89 Hz, 1H), 7.12-7.20 (m, 1H), 6.90 (d, J=7.65 Hz, 1H), 6.86 (d, J=8.03 Hz, 1H), 4.09 (dd, J=3.89, 5.40 Hz, 2H), 3.66-3.74 (m, 2H), 3.12-3.23 (m, 1H), 2.65-2.88 (m, 3H), 2.57 (br d, J=8.28 Hz, 1H), 2.20 (s, 3H), 1.95 (br s, 1H), 1.78-1.90 (m, 1H).

[0483] Example 72: 6-(2-chloro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0484] Intermediate 16o: 6-(2-chloro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16o was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (2-chloro-3-methoxyphenyl)boronic acid pinacol ester (134.46 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16o (190.00 mg, crude) was obtained as a yellow oily substance. m / z(M+H) + = 367.0, 369.0.

[0485] Example 72: 6-(2-chloro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 72 was prepared using intermediate 16o (190.00 mg, 517.99 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 72 (29.90 mg, 80.42 μmol, 15.53% yield) was obtained as a white solid.

[0486] 1H-NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.01 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.83 Hz, 1H), 7.45-7.51 (m, 2H), 7.41 (t, J=7.40 Hz, 2H), 7.30-7.35 (m, 1H), 7.13-7.19 (m, 1H), 6.94 (d, J=8.16 Hz, 1H), 6.91 (d, J=7.78 Hz, 1H), 5.11 (s, 2H), 3.13-3.25 (m, 1H), 2.65-2.88 (m, 3H), 2.56 (br d, J=9.41 Hz, 1H), 2.24 (s, 3H), 1.95 (br s, 1H), 1.77-1.90 (m, 1H).

[0487] Example 73: 6-(5-methoxy-2-(trifluoromethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0488] Intermediate 16p: 6-(5-methoxy-2-(trifluoromethyl)phenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16p was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (5-methoxy-2-(trifluoromethyl)phenyl)boronic acid pinacol ester (242.14 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16p (72.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 401.1.

[0489] Example 73: 6-(5-Methoxy-2-(trifluoromethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 73 was prepared using intermediate 16p (72.00 mg, 179.84 μmol) as the starting material, following the same method as described in, for example, 58, and Example 73 (8.30 mg, 19.84 μmol, 11.03% yield) was obtained as a white solid.

[0490] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.8 Hz, 1H), 7.13 (d, J=8.3 Hz, 1H), 6.78 (d, J=2.5 Hz, 1H), 6.72 (dd, J=2.6, 8.3 Hz, 1H), 3.81 (s, 3H), 3.19 - 2.99 (m, 2H), 2.88 - 2.78 (m, 1H), 2.75 - 2.61 (m, 2H), 2.32 (s, 3H), 2.21 - 2.10 (m, 1H), 1.94 - 1.81 (m, 1H)

[0491] Example 74: 6-(2-fluoro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0492] Intermediate 16q: 6-(2-fluoro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16q was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (2-fluoro-5-methoxyphenyl)boronic acid pinacol ester (122.60 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16q (60.00 mg, crude) was obtained as a brown solid. m / z(M+H) + = 351.0.

[0493] Example 74: 6-(2-fluoro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 74 was prepared using intermediate 16q (60.00 mg, 171.26 μmol) as the starting material, following the same method as described, for example, in 58, and Example 74 (7.70 mg, 21.66 μmol, 12.65% yield) was obtained as a white solid.

[0494] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.9 Hz, 2H), 7.70 (s, 1H), 7.43 (t, J=4.8 Hz, 1H), 7.10 (d, J=7.7 Hz, 1H), 7.04 - 6.97 (m, 2H), 3.20 - 3.10 (m, 1H), 3.04 (br dd, J=5.1, 19.4 Hz, 1H), 2.86 - 2.61 (m, 3H), 2.34 (s, 6H), 2.18 - 2.09 (m, 1H), 1.95 - 1.83 (m, 1H).

[0495] Example 75: 6-(2-chloro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0496] Intermediate 16r: 6-(2-chloro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16r was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (2-chloro-5-methoxyphenyl)boronic acid pinacol ester (193.72 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16r (160.00 mg, crude) was obtained as a brown solid. m / z(M+H) + = 367.0, 369.0.

[0497] Example 75: 6-(2-chloro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 75 was prepared using intermediate 16r (160.00 mg, 436.21 μmol) as the starting material, following the same method as described in, for example, 58, and Example 75 (5.80 mg, 15.65 μmol, 3.59% yield) was obtained as a white solid.

[0498] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.9 Hz, 2H), 7.71 (s, 1H), 7.42 (t, J=4.8 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 6.82 (d, J=2.9 Hz, 1H), 6.76 (dd, J=2.9, 8.7 Hz, 1H), 3.82 (s, 3H), 3.48 - 3.37 (m, 1H), 3.08 - 2.93 (m, 2H), 2.76 - 2.57 (m, 2H), 2.25 - 2.16 (m, 1H), 1.97 - 1.84 (m, 1H).

[0499] Example 76: 6-(2-methoxy-5-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0500] Intermediate 16s: 6-(2-methoxy-5-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16s was prepared using intermediate 15b (200.00 mg, 480.91 μmol) and (5-methoxy-2-methylphenyl)boronic acid (119.73 mg, 721.37 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16s (120.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 347.1.

[0501] Example 76: 6-(2-methoxy-5-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 76 was prepared using intermediate 16s (120.00 mg, 346.44 μmol) as the starting material, in the same manner as described, for example, in 58, and Example 76 (15.00 mg, 54.38 μmol, 15.70% yield) was obtained as a white solid.

[0502] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.8 Hz, 2H), 7.69 (s, 1H), 7.41 (t, J=4.9 Hz, 1H), 7.07 - 6.98 (m, 2H), 6.81 (d, J=8.3 Hz, 1H), 3.83 (s, 3H), 3.39 - 3.26 (m, 1H), 3.06 - 2.85 (m, 2H), 2.73 - 2.59 (m, 2H), 2.31 (s, 3H), 2.14 (br dd, J=3.5, 13.3 Hz, 1H), 1.99 - 1.87 (m, 1H).

[0503] Example 77: 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0504] Intermediate 16t: 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16t was prepared using intermediate 15b (250.00 mg, 500.95 μmol) and (2-methyl-5-(pyrrolidine-1-yl)phenyl)boronic acid pinacol ester (334.07 mg, 751.43 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16t (110.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 386.2.

[0505] Example 77: 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 77 was prepared using intermediate 16t (110.00 mg, 285.37 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 77 (9.84 mg, 24.20 μmol, 8.48% yield) was obtained as a yellow solid.

[0506] 1H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.8 Hz, 1H), 7.09 - 7.03 (m, 1H), 6.46 - 6.40 (m, 2H), 3.31 - 3.25 (m, 4H), 3.18 - 3.01 (m, 2H), 2.87 - 2.62 (m, 3H), 2.28 (s, 3H), 2.21 - 2.14 (m, 1H), 2.01 (td, J=3.3, 6.6 Hz, 4H), 1.95 - 1.84 (m, 1H).

[0507] Example 78: 6-(1-methylindolin-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0508] Intermediate 16u: 6-(1-methylindoline-4-yl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16u was prepared using intermediate 15b (250.00 mg, 500.94 μmol) and (1-methylindoline-4-yl)boronic acid pinacol ester (241.60 mg, 751.41 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16u (140.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 358.2.

[0509] Example 78: 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 78 was prepared using intermediate 16u (140.00 mg, 391.71 μmol) as a starting material, following the same method as described in, for example, 58, and Example 78 (26.79 mg, 71.41 μmol, 18.23% yield) was obtained as a yellow solid.

[0510] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.9 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.9 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.92 (dd, J=2.5, 8.3 Hz, 1H), 6.86 (d, J=2.5 Hz, 1H), 3.79 - 3.66 (m, 1H), 3.19 - 3.09 (m, 1H), 3.08 - 2.98 (m, 1H), 2.87 - 2.78 (m, 1H), 2.74 - 2.61 (m, 2H), 2.32 (s, 3H), 2.19 - 2.10 (m, 1H), 1.93 - 1.79 (m, 1H), 0.79 - 0.76 (m, 4H).

[0511] Example 79: 6-(2-fluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0512] Intermediate 16v: 6-(2-fluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16v was prepared using intermediate 15b (250.00 mg, 500.95 μmol) and (2-fluoro-3-methoxyphenyl)boronic acid pinacol ester (189.43 mg, 751.42 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16v (140.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 351.0.

[0513] Example 79: 6-(2-fluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 79 was prepared using intermediate 16v (140.00 mg, 399.60 μmol) as a starting material, following the same method as described in, for example, 58, and Example 79 (9.04 mg, 25.45 μmol, 6.37% yield) was obtained as a white solid.

[0514] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.9 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.8 Hz, 1H), 7.31 - 7.27 (m, 1H), 7.00 (dd, J=1.7, 8.2 Hz, 1H), 6.93 (t, J=1.9 Hz, 1H), 6.88 (d, J=7.7 Hz, 1H), 3.79 - 3.70 (m, 1H), 3.05 - 2.85 (m, 3H), 2.80 - 2.60 (m, 2H), 2.29 - 2.17 (m, 1H), 1.95 - 1.81 (m, 1H), 0.83 - 0.77 (m, 4H).

[0515] Example 80: 6-(5-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0516] Intermediate 16w: 6-(5-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16w was prepared using intermediate 15b (250.00 mg, 500.94 μmol) and (5-methoxy-2-methylphenyl)boronic acid (124.72 mg, 751.41 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16w (110.00 mg, crude) was obtained as a brown solid. m / z(M+H) + = 347.1

[0517] Example 80: 6-(5-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 80 was prepared using intermediate 16w (110.00 mg, 317.57 μmol) as a starting material, in the same manner as described, for example, in 58, and Example 80 (23.99 mg, 68.58 μmol, 21.60% yield) was obtained as a white solid.

[0518] 1H-NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 9.02 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.89 Hz, 1H), 7.16 (t, J=7.91 Hz, 1H), 6.90 (d, J=7.53 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 6.08 (tdd, J=4.99, 10.42, 17.25 Hz, 1H), 5.43 (dd, J=1.76, 17.32 Hz, 1H), 5.26 (dd, J=1.69, 10.60 Hz, 1H), 4.56 (d, J=4.89 Hz, 2H), 3.12-3.24 (m, 1H), 2.65-2.87 (m, 3H), 2.56 (br d, J=8.53 Hz, 1H), 2.22 (s, 3H), 1.95 (br s, 1H), 1.79-1.91 (m, 1H).

[0519] Example 81: 6-(2,5-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0520] Intermediate 16x: 6-(2,5-dimethylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16x was prepared using intermediate 15b (250.00 mg, 500.94 μmol) and (2,5-dimethylphenyl)boronic acid (112.70 mg, 751.41 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16x (75.00 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 331.2.

[0521] Example 81: 6-(2,5-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 81 was prepared using intermediate 16x (75.00 mg, 227.01 μmol) as the starting material, following the same method as described, for example, in 58, and Example 81 (16.9 mg, 50.69 μmol, 22.33% yield) was obtained as a white solid.

[0522] 1 H-NMR (400 MHz, CDCl3) δ 8.18 (s, 2H), 7.78 (s, 1H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.91 Hz, 1H), 6.85 (d, J=8.03 Hz, 1H), 3.78 (s, 3H), 3.27-3.34 (m, 4H), 3.13-3.22 (m, 1H), 2.65-2.83 (m, 3H), 2.52-2.58 (m, 1H), 2.18 (s, 3H), 1.91-2.05 (m, 5H), 1.77-1.89 (m, 1H).

[0523] Example 82: 6-(2,3-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0524] Intermediate 16y:6-(2,3-dimethylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16y was prepared using intermediate 15b (250.00 mg, 500.94 μmol) and (2,3-dimethylphenyl)boronic acid (112.70 mg, 751.41 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16y (100.00 mg, crude) was obtained as a yellow solid. m / z(M+H) += 331.2.

[0525] Example 82: 6-(2,3-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 82 was prepared using intermediate 16y (100.00 mg, 302.68 μmol) as the starting material, following the same method as described, for example, in 58, and Example 82 (4.78 mg, 13.70 μmol, 4.53% yield) was obtained as a yellow solid.

[0526] 1 H-NMR (400 MHz, DMSO-d6) δ 8.61 (s, 2H), 7.81 (s, 1H), 7.14-7.22 (m, 1H), 6.88 (dd, J=7.91, 16.81 Hz, 2H), 3.75-3.82 (m, 7H), 3.34 (br s, 4H), 3.12-3.22 (m, 1H), 2.76-2.86 (m, 1H), 2.63-2.75 (m, 2H), 2.56 (br s, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.77-1.90 (m, 1H).

[0527] Example 83: 6-(3-(methoxymethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0528] Intermediate 16z: 6-(3-(methoxymethyl)phenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16z was prepared using intermediate 15b (590 mg, 1.18 mmol) and (3-(methoxymethyl)phenyl)boronic acid (196.23 mg, 1.18 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16z (280 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 347.1.

[0529] Example 83: 6-(3-(methoxymethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 83 was prepared using intermediate 16z (260 mg, 750.62 μmol) as the starting material, following the same method as described, for example, in 58, and Example 83 (24.91 mg, 70.28 μmol, 9.36% yield) was obtained as a white solid.

[0530] 1 H-NMR (400 MHz, DMSO-d6) δ 8.72 (s, 2H), 7.82 (s, 1H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.65 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 5.03 (t, J=5.46 Hz, 1H), 4.24-4.31 (m, 2H), 3.75-3.80 (m, 5H), 3.13-3.22 (m, 1H), 2.67-2.86 (m, 3H), 2.55 (br d, J=9.79 Hz, 1H), 2.18 (s, 3H), 1.93 (br s, 1H), 1.78-1.89 (m, 1H).

[0531] Example 84: 6-(5-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0532] Intermediate 16aa: 6-(5-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16aa was prepared using intermediate 15b (200 mg, 523.65 μmol) and (5-cyclopropoxy-2-methylphenyl)boronic acid pinacol ester (244.71 mg, 785.47 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16aa (210 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 373.2.

[0533] Example 84: 6-(5-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 84 was prepared using intermediate 16aa (210 mg, 563.88 μmol) as the starting material, following the same method as described, for example, in 58, and Example 84 (13.78 mg, 36.77 μmol, 6.52% yield) was obtained as a white solid.

[0534] 1 H-NMR (400 MHz, DMSO-d6) δ 8.35 (d, J=6.15 Hz, 1H), 7.77 (s, 1H), 7.15-7.21 (m, 1H), 6.96 (d, J=6.27 Hz, 1H), 6.89 (d, J=7.78 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 3.79 (s, 3H), 3.67 (br d, J=5.02 Hz, 4H), 3.62 (br d, J=4.77 Hz, 4H), 3.17 (br t, J=8.97 Hz, 1H), 2.62-2.83 (m, 3H), 2.52-2.59 (m, 1H), 2.18 (s, 3H), 1.93 (br s, 1H), 1.83 (dq, J=4.83, 11.90 Hz, 1H).

[0535] Example 85: 6-(3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0536] Intermediate 16ab: 6-(3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ab was prepared using intermediate 15b (200 mg, 523.65 μmol) and (3-cyclopropoxyphenyl)boronic acid pinacol ester (241.24 mg, 785.48 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ab (170 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 359.2.

[0537] Example 85: 6-(3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 85 was prepared using intermediate 16ab (170 mg, 474.34 μmol) as the starting material, following the same method as described, for example, in 58, and Example 85 (12.36 mg, 33.03 μmol, 6.96% yield) was obtained as a white solid.

[0538] 1H-NMR (400 MHz, CDCl3) δ 8.93 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.9 Hz, 1H), 7.27 - 7.22 (m, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.80 - 6.76 (m, 2H), 4.78 (qd, J=2.9, 5.7 Hz, 1H), 3.03 - 2.84 (m, 3H), 2.80 - 2.71 (m, 1H), 2.71 - 2.60 (m, 1H), 2.26 - 2.16 (m, 1H), 1.96 - 1.78 (m, 7H), 1.68 - 1.59 (m, 2H).

[0539] Example 86: 6-(3-(cyclopentyloxy)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0540] Intermediate 16ac: 6-(3-(cyclopentyloxy)phenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ac was prepared using intermediate 15b (300 mg, 785.48 μmol) and (3-(cyclopentyloxy)phenyl)boronic acid pinacol ester (425.50 mg, 1.18 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ac (240 mg, crude) was obtained as a yellow solid. m / z(M+H) + = 387.1.

[0541] Example 86: 6-(3-(cyclopentyloxy)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 86 was prepared using intermediate 16ac (240 mg, 621.04 μmol) as the starting material, following the same method as described, for example, in 58, and Example 86 (29.15 mg, 73.01 μmol, 11.76% yield) was obtained as a white solid.

[0542] 1 H-NMR (400 MHz, CDCl3) δ 8.93 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J=4.9 Hz, 1H), 7.27 - 7.22 (m, 1H), 6.82 (d, J=7.8 Hz, 1H), 6.80 - 6.76 (m, 2H), 4.78 (qd, J=2.9, 5.7 Hz, 1H), 3.03 - 2.84 (m, 3H), 2.80 - 2.71 (m, 1H), 2.71 - 2.60 (m, 1H), 2.26 - 2.16 (m, 1H), 1.96 - 1.78 (m, 7H), 1.68 - 1.59 (m, 2H).

[0543] Example 87: 6-(4-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0544] Intermediate 16ad: 6-(4-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ad was prepared using intermediate 15b (0.3 g, 801.51 μmol) and (4-methoxy-2-methylphenyl)boronic acid (133.04 mg, 801.51 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ad (0.2 g, crude) was obtained as a yellow solid. m / z(M+H) + =347.1

[0545] 1 H NMR (DMSO-d6, 400 MHz) δ 9.02 (d, J = 4.8 Hz, 2H), 8.00 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 6.86 (d, J = 2.4 Hz, 1H), 6.81 (dd, J = 8.4, 2.4 Hz, 1H), 6.40 (s, 1H), 3.75 (s, 3H), 2.75-2.85 (m, 2H), 2.60-2.70 (m, 2H), 2.36 (s, 3H).

[0546] Example 87: 6-(4-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 87 was prepared using intermediate 16ad (0.15 g, 433.05 μmol) as the starting material, in the same manner as described, for example, in 58, and Example 87 (42 mg, 120.55 μmol, 27.84% yield) was obtained as a white solid.

[0547] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.85 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 7.13-7.23 (m, 1H), 6.77 (br d, J = 2.8 Hz, 2H), 3.72 (s, 3H), 3.07 (m, 1H), 2.57-2.85 (m, 4H), 2.32 (s, 3H), 1.78-1.99 (m, 2H).

[0548] Example 88: 6-(1,5-dimethyl-1H-indazol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0549] Intermediate 16ae: 6-(1,5-dimethyl-1H-indazol-4-yl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ae was prepared using intermediate 15b (0.2 g, 534.34 μmol) and (1,5-dimethyl-1H-indazol-4-yl)boronic acid pinacol ester (145.42 mg, 534.34 μmol) according to the method described for intermediate 16a, and intermediate 16ae (50 mg, 134.99 μmol, 25.26% yield) was obtained as a yellow solid. m / z(M+H) + = 371.2.

[0550] Example 88: 6-(1,5-dimethyl-1H-indazol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 88 was prepared using intermediate 16ae (51.39 mg, 138.73 μmol) as a starting material, following the same method as described in, for example, 58, and Example 88 (4 mg, 10.74 μmol, 7.74% yield) was obtained as a bright yellow solid.

[0551] 1 H-NMR (400 MHz, DMSO-d6) δ 9.03 (d, J = 4.8 Hz, 3H), 8.24 (s, 1H), 7.85 (s, 1H), 7.68-7.76 (m, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 4.01 (s, 3H), 3.19 (m, 1H), 3.12-3.12 (m, 1H), 2.73-2.94 (m, 4H), 2.44 (s, 3H), 1.99 (m, 2H).

[0552] Example 89: 6-Mesityl-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0553] Intermediate 16af: 6-Mesityl-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16af was prepared using intermediate 15b (200.00 mg, 534.34 μmol) and mesitylboronic acid (87.64 mg, 534.34 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16af (0.15 g, 435.53 μmol, 81.51% yield) was obtained as a yellow solid. m / z(M+H)+ = 345.3;

[0554] 1 H NMR (DMSO-d6, 400 MHz) δ 9.03 (d, J = 4.8 Hz, 2H), 7.99 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 6.92 (s, 2H), 6.26 (s, 1H), 2.78-2.91 (m, 2H), 2.52-2.56 (m, 2H), 2.24 (s, 3H), 2.20 (s, 6H).

[0555] Example 89: 6-Mesityl-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 89 was prepared using intermediate 16af (150.00 mg, 435.53 μmol) as a starting material, following the same method as described in, for example, 58, and Example 89 (8 mg, 22.61 μmol, 5.19% yield) was obtained as a white solid.

[0556] 1H-NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 4.8 Hz, 2H), 7.81 (s, 1H), 7.67-7.73 (m, 1H), 6.81 (s, 2H), 3.28-3.30 (m, 1H), 2.95-3.08 (m, 1H), 2.64-2.84 (m, 2H), 2.32 (s, 6H), 2.18 (s, 3H), 1.89 (m, 2H).

[0557] Example 90: 6-(2,6-difluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0558] Intermediate 16ag: 6-(2,6-difluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ag was prepared using intermediate 15b (0.2 g, 534.34 μmol) and (2,6-difluoro-3-methoxyphenyl)boronic acid (100.42 mg, 534.34 μmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ag (0.15 g, 407.24 μmol, 76.21% yield) was obtained as a yellow solid. m / z(M+H) + = 369.1

[0559] 1 H NMR (DMSO-d6, 400 MHz) δ 9.03 (d, J = 4.8 Hz, 2H), 8.04 (s, 1H), 7.72 (t, J = 4.8 Hz, 1H), 7.06-7.34 (m, 2H), 6.71 (s, 1H), 3.86 (s, 3H), 2.76-2.89 (m, 2H), 2.62-2.73 (m, 2H).

[0560] Example 90: 6-(2,6-difluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 90 was prepared using 16g (0.15g, 407.24μmol) of intermediate as a starting material, in the same manner as described, for example, in 58, and Example 90 (60mg, 162.01μmol, 39.78% yield) was obtained as a white solid.

[0561] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.83 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 6.99-7.19 (m, 3H), 3.83 (s, 3H), 3.36-3.43 (m, 1H), 2.71-3.04 (m, 4H), 1.97-2.18 (m, 3H).

[0562] Example 91: 6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0563] Intermediate 16ah: 6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ah was prepared using intermediate 15b (2.50 g, 6.68 mmol) and (2-chloro-3-cyclopropoxyphenyl)boronic acid pinacol ester (1.83 g, 6.21 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ah (1.60 g, 3.84 mmol, 57.4% yield) was obtained as a yellow solid.

[0564] 1H NMR (400MHz, CDCl3) δ 8.94 (d, J = 4.8 Hz, 2H), 7.79 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.35 - 7.30 (m, 1H), 7.29 - 7.24 (m, 2H), 6.91 (dd, J = 1.6, 7.6 Hz, 1H), 6.35 (t, J = 1.6 Hz, 1H), 3.84 (tt, J = 3.2, 5.9 Hz, 1H), 3.08 - 2.98 (m, 2H), 2.84 - 2.72 (m, 2H), 0.92 - 0.82 (m, 4H).

[0565] Example 91: 6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 91 was prepared using intermediate 16ah (1.20 g, 2.88 mmol) as the starting material, following the same method as described, for example, in 58, and Example 91 (517 mg, 1.26 mmol, 43.9% yield) was obtained as a white solid.

[0566] 1 H-NMR (400 MHz, CDCl3) δ 8.93 (d, J = 4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.26 - 7.22 (m, 2H), 6.95 - 6.86 (m, 1H), 3.83 (tt, J = 3.0, 5.8 Hz, 1H), 3.58 - 3.47 (m, 1H), 3.04 - 2.92 (m, 2H), 2.82 - 2.57 (m, 2H), 2.24 - 2.14 (m, 1H), 1.99 - 1.86 (m, 1H), 0.93 - 0.80 (m, 4H).

[0567] Example 92: 6-(1-cyclopropylindolin-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0568] Intermediate 16ai:6-(1-cyclopropylindorin-4-yl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ai was prepared using intermediate 15b (2.00 g, 5.34 mmol) and 1-cyclopropylindoline-4-yl)boronic acid pinacol ester (1.50 g, 5.26 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ai (1.70 g, 4.43 mmol, 83.0% yield) was obtained as a yellow solid. m / z(M+H) + = 384.0

[0569] Example 92: 6-(1-cyclopropylindoline-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 92 was prepared using intermediate 16ai (1.70 g, 4.43 mmol) as a starting material, following a procedure similar to that of 58, for example, and Example 92 (230 mg, 549.19 μmol, 35.10% yield) was obtained as a pale yellow solid.

[0570] 1H-NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.8 Hz, 1H), 8.97 - 8.90 (m, 1H), 7.69 (s, 1H), 7.42 (t, J = 5.0 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 7.6 Hz, 1H), 3.46 - 3.39 (m, 2H), 3.06 - 2.89 (m, 4H), 2.85 - 2.59 (m, 3H), 2.19 - 2.11 (m, 2H), 1.95 - 1.83 (m, 1H), 0.73 - 0.63 (m, 4H).

[0571] Example 93: 6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0572] Intermediate 16aj: 6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16aj was prepared using intermediate 15c (3.00 g, 7.49 mmol) and (3-cyclopropoxy-2-methylphenyl)boronic acid pinacol ester (2.25 g, 7.49 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16aj (2.10 g, 5.28 mmol, 70.5% yield) was obtained as a yellow solid.

[0573] 1H NMR (400MHz, CDCl3) δ 8.74 (s, 2H), 7.75 (s, 1H), 7.25 - 7.16 (m, 2H), 6.81 (dd, J = 1.8, 7.0 Hz, 1H), 6.23 (s, 1H), 3.80 - 3.73 (m, 1H), 3.03 - 2.94 (m, 2H), 2.72 - 2.63 (m, 2H), 2.43 (s, 3H), 2.18 (s, 3H), 0.85 - 0.73 (m, 4H).

[0574] Example 93: 6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 93 was prepared using intermediate 16aj (1.20 g, 3.02 mmol) as a starting material, following the same method as described, for example, in 58, and Example 93 (500 mg, 1.27 mmol, 42.1% yield) was obtained as a white solid.

[0575] 1 H-NMR (400 MHz, CDCl3) δ 8.74 (s, 2H), 7.68 (s, 1H), 7.24 - 7.13 (m, 2H), 6.86 (d, J = 6.5 Hz, 1H), 3.78 - 3.71 (m, 1H), 3.26 - 3.17 (m, 1H), 3.04 - 2.95 (m, 1H), 2.86 - 2.76 (m, 1H), 2.75 - 2.60 (m, 2H), 2.43 (s, 3H), 2.19 (s, 3H), 2.17 - 2.09 (m, 1H), 1.95 - 1.82 (m, 1H), 0.82 - 0.76 (m, 4H).

[0576] Example 94: 6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method A. [ka]

[0577] Intermediate 16ak: 6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ak was prepared using intermediate 15c (3.00 g, 7.49 mmol) and (2-chloro-3-methoxyphenyl)boronic acid pinacol ester (1.40 g, 7.49 mmol) as starting materials, according to the method described for intermediate 16a, and intermediate 16ak (2.40 g, 6.15 mmol, 82.1% yield, 97.6% purity) was obtained as a yellow solid.

[0578] 1 H NMR (400MHz, CDCl3) δ 8.75 (s, 2H), 7.83 - 7.74 (m, 1H), 7.33 - 7.21 (m, 1H), 7.04 - 6.81 (m, 2H), 6.36 (s, 1H), 4.10 - 3.89 (m, 3H), 3.18 - 2.96 (m, 2H), 2.88 - 2.73 (m, 2H), 2.44 (s, 3H).

[0579] Example 94: 6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 94 was prepared using intermediate 16ak (600 mg, 1.54 mmol) as the starting material, following the same method as described, for example, in 58, and Example 94 (230 mg, 588 μmol, 38.2% yield, 97.8% purity) was obtained as a white solid.

[0580] 1H-NMR (400 MHz, CDCl3) δ 8.73 (s, 2H), 7.69 (s, 1H), 7.26 - 7.23 (m, 1H), 6.88 (dd, J = 4.4, 8.0 Hz, 2H), 3.93 (s, 3H), 3.61 - 3.49 (m, 1H), 3.02 - 2.92 (m, 2H), 2.82 - 2.58 (m, 2H), 2.43 (s, 3H), 2.19 (td, J = 2.8, 10.0 Hz, 1H), 1.98 - 1.85 (m, 1H).

[0581] Example 95: 6-(2-chloro-4-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method B. [ka]

[0582] Intermediate 17a: 2-(pyrimidine-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step x, intermediate 15b (1 g, 2.67 mmol, 1 eq), Pd(dppf)Cl2 (97.74 mg, 133.58 μmol, 0.05 eq), and KOAc (524.41 mg, 5.34 mmol, 2 eq) were dissolved in dioxane (20 mL), to which Pin2B2 (1.02 g, 4.01 mmol, 1.5 eq) was added all at once at 25 °C under N2. This mixture was stirred at 100 °C for 12 hours. This mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the residue. This residue was purified by silica gel chromatography (PE:SiO=1:1) to obtain intermediate 17a (0.85 g, 2.41 mmol, 90.33% yield) as a yellow solid. m / z(M+H) + = 353.3

[0583] 1H NMR (CDCl3, 400 MHz) δ 8.92 (d, J = 4.8 Hz, 2H), 7.77 (s, 1H), 7.41 (t, J = 4.8 Hz, 1H), 6.99 (s, 1H), 2.74-2.89 (t, J = 8.8 Hz, 2H), 2.46-2.61 (t, J = 8.8 Hz, 2H), 1.32 (s, 12H).

[0584] Intermediate 16al:6-(2-chloro-4-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step xi, a mixture of intermediate 17a (247.04 mg, 1.20 mmol, 64.34 μL, 1.5 eq) and 1-bromo-2-chloro-4-methylbenzene (0.3 g, 801.51 μmol, 1 eq) in dioxane (10 mL) was to be added all at once to a solution of Na2CO3 (339.80 mg, 3.21 mmol, 4 eq) in H2O (1 mL) and Pd(dppf)Cl2.CH2Cl2 (65.45 mg, 80.15 μmol, 0.1 eq) at 20 °C under N2. The mixture was stirred at 100 °C for 12 hours. The mixture was filtered and concentrated under vacuum. This residue was purified by silica gel chromatography (PE:SiO=0:1, 1:0) to obtain an intermediate 16al (0.15g, 427.59μmol, 53.35% yield) as a yellow solid.

[0585] 1 H NMR (400MHz, CDCl3) δ 9.07-9.03 (m, 3H), 8.04 (s, 1H), 7.76-7.68 (m, 2H), 7.40 (s, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.57 (s, 1H), 2.87-2.79 (m, 2H), 2.77-2.67 (m, 2H), 2.35 (s, 3H).

[0586] Example 95: 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 95 was prepared using intermediate 16al (0.15 g, 427.59 μmol) as the starting material, following the same method as described in, for example, 58, and Example 95 (0.018 g, 51.02 μmol, 11.93% yield) was obtained as a white solid.

[0587] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.0 Hz, 2H), 7.71 (s, 1H), 7.42 (t, J = 4.4 Hz, 1H), 7.25 (s, 1H), 7.17-7.12 (m, 1H), 7.12-7.06 (m, 1H), 3.52-3.39 (m, 1H), 3.04-2.92 (m, 2H), 2.76-2.58 (m, 2H), 2.34 (s, 3H), 2.22-2.05 (m, 2H), 1.97-1.85 (m, 1H).

[0588] Example 96: 6-(3-(dimethylamino)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method B. [ka]

[0589] Intermediate 16am: 6-(3-(dimethylamino)-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step xi, intermediate 16am was prepared using intermediate 17a (0.2 g, 567.87 μmol) and 3-bromo-N,N,2-trimethylaniline (121.58 mg, 567.87 μmol) as starting materials, in the same manner as described for intermediate 16al, and intermediate 16am (0.15 g, 417.33 μmol, 73.49% yield) was obtained as a yellow solid. m / z(M+H) + = 360.3

[0590] 1 H NMR (CDCl3, 400 MHz) δ 8.94 (d, J = 4.9 Hz, 3H), 7.78 (s, 1H), 7.44-7.40 (m, 2H), 7.20 (t, J = 8.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 7.6 Hz, 1H), 6.26 (s, 1H), 2.96-3.07 (m, 2H), 2.66-2.76 (m, 8H), 2.35 (s, 3H).

[0591] Example 96: 6-(3-(dimethylamino)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 96 was prepared using intermediate 16am (0.15 g, 417.33 μmol) as the starting material, following the same method as described, for example, in 58, and Example 96 (14 mg, 34.93 μmol, 8.37% yield) was obtained as a white solid.

[0592] 1H-NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.8 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.28 (m, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 3.16 (m, 1H), 2.97-2.92 (m, 1H), 2.91-2.75 (m, 7H), 2.65-2.59 (m, 2H), 2.35 (s, 3H), 2.082.06 (m, 1H), 1.86-1.81 (m, 1H).

[0593] Example 97: 6-(5-methoxy-2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method B. [ka]

[0594] Intermediate 16an: 6-(5-methoxy-2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step xi, intermediate 16an was prepared using intermediate 17a (0.3 g, 851.80 μmol) and 1-bromo-5-methoxy-2,4-dimethylbenzene (183.21 mg, 851.80 μmol) as starting materials, in the same manner as described for intermediate 16al, and intermediate 16an (0.2 g, 554.93 μmol, 65.15% yield) was obtained as a yellow solid. m / z(M+H) + = 361.3

[0595] 1H NMR (CDCl3, 400 MHz) δ 9.03 (d, J = 4.8 Hz, 2H), 8.01 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 7.04 (s, 1H), 6.80 (s, 1H), 6.44 (s, 1H), 3.79 (s, 3H), 2.76-2.89 (m, 2H), 2.61-2.73 (m, 2H), 2.26 (s, 3H), 2.14 (s, 3H).

[0596] Example 97: 6-(5-methoxy-2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 97 was prepared using intermediate 16nj (0.2 g, 554.93 μmol) as the starting material, in the same manner as described, for example, in 58, and Example 97 (8 mg, 22.07 μmol, 3.98% yield) was obtained as a white solid.

[0597] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.4 Hz, 2H), 7.86 (s, 1H), 7.71 (t, J = 4.4 Hz, 1H), 6.93 (s, 1H), 6.83 (s, 1H), 3.77 (s, 3H), 3.07 (m, 1H), 2.72-2.88 (m, 4H), 2.23 (s, 3H), 2.09 (s, 3H), 1.78-2.01 (m, 2H).

[0598] Example 98: 6-(4-chloro-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method B. [ka]

[0599] Intermediate 16ao: 6-(4-chloro-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step viiii, intermediate 16ao was prepared using intermediate 15b (0.3 g, 801.51 μmol) and (4-chloro-2-methylphenyl)boronic acid (136.58 mg, 801.51 μmol) as starting materials, according to the method described for intermediate 16a in Example 58, and intermediate 16ao (0.15 g, 427.59 μmol, 53.35% yield) was obtained as a yellow solid. m / z(M+H) + = 351.1.

[0600] Example 98: 6-(4-chloro-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 2, step ix, Example 98 was prepared using intermediate 16ao (120 mg, 342.07 μmol) as the starting material, in the same manner as described, for example, in 58, and Example 98 (13 mg, 36.85 μmol, 10.77% yield) was obtained as a white solid.

[0601] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.85 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 7.22-7.34 (m, 3H), 3.14 (m, 1H), 2.65-2.89 (m, 4H), 2.36 (s, 2H), 1.81-2.01 (m, 2H).

[0602] Example 99: 6-(4-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 2, Method B. [ka]

[0603] Intermediate 16ap: 6-(4-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one According to Scheme 2, step xi, intermediate 16ap was prepared using intermediate 17a (0.3 g, 851.80 μmol) and 1-(4-bromo-3-methylphenyl)ethane-1-one (181.49 mg, 851.80 μmol) as starting materials, in the same manner as described for intermediate 16al, and intermediate 16ap (0.18 g, 502.24 μmol, 58.96% yield) was obtained as a yellow solid. m / z(M+H) + = 359.2

[0604] 1 H NMR (DMSO-d6, 400 MHz) δ 9.03 (d, J = 4.8 Hz, 2H), 8.03 (s, 1H), 7.88 (s, 1H), 7.83 (br d, J = 8.0 Hz, 1H), 7.72 (t, J = 4.8 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 6.52 (s, 1H), 2.80-2.89 (m, 2H), 2.66-2.75 (m, 2H), 2.59 (s, 3H), 2.44 (s, 3H).

[0605] Example 99: 6-(4-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step ix, Example 99 was prepared using intermediate 16ap (150.00 mg, 418.53 μmol) as the starting material, following the same method as described, for example, in 58, and Example 99 (22 mg, 61.04 μmol, 14.58% yield) was obtained as a white solid.

[0606] 1H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.85 (s, 1H), 7.76-7.83 (m, 2H), 7.71 (t, J = 4.8 Hz, 1H), 7.43 (br d, J = 8.0 Hz, 1H), 3.16-3.27 (m, 1H), 2.65-2.93 (m, 4H), 2.55 (s, 3H), 2.43 (s, 3H), 1.83-2.03 (m, 2H).

[0607] Example 100: 6-(3-(3-methoxypropoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0608] Intermediate 50: 6-(3-hydroxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 5, step i, BBr3 (8.99 g, 35.90 mmol, 3.46 mL, 5.00 eq) was added dropwise to a solution of Compound Example 40 (2.50 g, 7.18 mmol, 1.00 eq) in CH2Cl2 (30.00 mL) under N2 at 0°C. The mixture was stirred at 0°C for 1.5 hours. This mixture was poured into H2O (80 mL) at 0°C. The pH of the aqueous phase was adjusted to approximately 6-7 by adding K2CO3 solid. A large precipitate was formed. This mixture was filtered, and the combined aqueous phase was extracted with CH2Cl2 (60 mL x 5), filtered, and concentrated under vacuum. The filtered cake was dissolved in CH2Cl2 / MeOH (1 / 10, 100 mL) and stirred for 1 hour. This mixture was filtered. All organic phases were combined and dried under vacuum. Intermediate 50 (2.60 g, 5.99 mmol, 83.39% yield) was obtained as a brown solid.

[0609] 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.01 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.89 Hz, 1H), 6.88-6.95 (m, 1H), 6.63-6.69 (m, 1H), 6.60 (d, J=7.65 Hz, 1H), 3.07-3.15 (m, 1H), 2.66-2.85 (m, 3H), 2.56 (s, 1H), 2.13 (s, 3H), 1.91-1.99 (m, 1H), 1.74-1.86 (m, 1H).

[0610] Example 100: (6-(3-(3-methoxypropoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 5, step ii, a mixture of intermediate 50 (80 mg, 239.26 μmol, 1 eq) and 1-bromo-3-methoxypropane (73.22 mg, 478.52 μmol, 38.27 μL, 2 eq) in DMF (2 mL) was to be combined with Cs2CO3 (116.93 mg, 358.89 μmol, 1.5 eq) in one addition under N2 at 25 °C. The mixture was stirred at 100 °C for 12 hours. The mixture was filtered, the filtrate was concentrated under reduced pressure, and purified by preparative HPLC to obtain Example 100 (25 mg, 61.50 μmol, 25.71% yield) as a white solid.

[0611] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.85 (s, 1H), 7.71 (t, J = 4.8 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H), 6.80-6.93 (m, 2H), 4.00 (t, J = 6.2 Hz, 2H), 3.51 (t, J = 6.2 Hz, 2H), 3.26 (s, 3H), 3.16-3.19 (m, 1H), 2.58-2.87 (m, 4H), 2.19 (s, 3H), 1.76-2.02 (m, 4H).

[0612] Example 101: 6-(3-ethoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0613] In accordance with Scheme 5, step ii, Example 101 was prepared using intermediate 50 (80 mg, 239.26 μmol) and iodoethane (74.63 mg, 478.51 μmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 101 (25 mg, 68.98 μmol, 28.83% yield) as a white solid.

[0614] 1 H-NMR (400 MHz, DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.84 (s, 1H), 7.71 (br t, J = 4.8 Hz, 1H), 7.15 (br t, J = 7.8 Hz, 1H), 7.07-7.26 (m, 1H), 6.85 (br dd, J=19.0, 7.8 Hz, 2H), 4.01 (q, J = 6.8 Hz, 2H), 3.16-3.18 (m, 1H), 2.56-2.93 (m, 4H), 2.19 (s, 3H), 1.75-2.03 (m, 2H), 1.36 (br t, J=6.8 Hz, 3H).

[0615] Example 102: 6-(3-(cyclopropylmethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0616] In accordance with Scheme 5, Step II, Example 102 was prepared using intermediate 50 (150.00 mg, 345.43 μmol) and (bromomethyl)cyclopropane (233.16 mg, 1.73 mmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 102 (58.63 mg, 150.78 μmol, 43.65% yield) as a white solid.

[0617] 1 H-NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.02 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.83 Hz, 1H), 7.10-7.17 (m, 1H), 6.88 (d, J=7.65 Hz, 1H), 6.81 (d, J=8.16 Hz, 1H), 3.82 (d, J=6.65 Hz, 2H), 3.12-3.23 (m, 1H), 2.65-2.87 (m, 3H), 2.52-2.62 (m, 1H), 2.21 (s, 3H), 1.94 (br s, 1H), 1.76-1.89 (m, 1H), 1.19-1.30 (m, 1H), 0.52-0.61 (m, 2H), 0.29-0.37 (m, 2H).

[0618] Example 103: 6-(3-isopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0619] In accordance with Scheme 5, step ii, Example 103 was prepared using intermediate 50 (180.00 mg, 414.51 μmol) and 2-bromopropane (352.31 mg, 2.07 mmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 103 (71.78 mg, 190.68 μmol, 46.00% yield) as a white solid.

[0620] 1 H-NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.02 (s, 1H), 7.85 (s, 1H), 7.72 (t, J=4.89 Hz, 1H), 7.12-7.18 (m, 1H), 6.88 (d, J=3.39 Hz, 1H), 6.86 (d, J=3.89 Hz, 1H), 4.43-4.71 (m, 1H), 3.12-3.22 (m, 1H), 2.66-2.86 (m, 3H), 2.56 (br d, J=9.91 Hz, 1H), 2.18 (s, 3H), 1.91-2.00 (m, 1H), 1.79-1.90 (m, 1H), 1.28 (d, J=6.02 Hz, 6H).

[0621] Example 104: 6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0622] In accordance with Scheme 5, step ii, Example 104 was prepared using intermediate 50 (150 mg, 345.42 μmol) and 2-bromocyclopropane (417.88 mg, 3.45 mmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 104 (19.84 mg, 51.56 μmol, 14.93% yield) as a white solid.

[0623] 1H-NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.02 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.89 Hz, 1H), 7.16 (t, J=7.91 Hz, 1H), 6.90 (d, J=7.53 Hz, 1H), 6.85 (d, J=8.16 Hz, 1H), 6.08 (tdd, J=4.99, 10.42, 17.25 Hz, 1H), 5.43 (dd, J=1.76, 17.32 Hz, 1H), 5.26 (dd, J=1.69, 10.60 Hz, 1H), 4.56 (d, J=4.89 Hz, 2H), 3.12-3.24 (m, 1H), 2.65-2.87 (m, 3H), 2.56 (br d, J=8.53 Hz, 1H), 2.22 (s, 3H), 1.95 (br s, 1H), 1.79-1.91 (m, 1H).

[0624] Example 105: 6-(3-(2-methoxyethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0625] In accordance with Scheme 5, step ii, Example 105 was prepared using intermediate 50 (200.00 mg, 460.57 μmol) and 1-bromo-2-methoxyethane (320.07 mg, 2.30 mmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 105 (41.81 mg, 106.54 μmol, 23.13% yield) as a white solid.

[0626] 1H-NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 9.02 (s, 1H), 7.86 (s, 1H), 7.72 (t, J=4.89 Hz, 1H), 7.12-7.20 (m, 1H), 6.90 (d, J=7.65 Hz, 1H), 6.86 (d, J=8.03 Hz, 1H), 4.09 (dd, J=3.89, 5.40 Hz, 2H), 3.66-3.74 (m, 2H), 3.12-3.23 (m, 1H), 2.65-2.88 (m, 3H), 2.57 (br d, J=8.28 Hz, 1H), 2.20 (s, 3H), 1.95 (br s, 1H), 1.78-1.90 (m, 1H).

[0627] Example 106: 6-(3-(benzyloxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 5. [ka]

[0628] In accordance with Scheme 5, step ii, Example 106 was prepared using intermediate 50 (180.00 mg, 414.51 μmol) and (bromomethyl)benzene (212.68 mg, 1.24 mmol) as starting materials, following the same method as described in, for example, 100, to obtain intermediate Example 106 (61.03 mg, 143.77 μmol, 34.68% yield) as a white solid.

[0629] 1H-NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 9.01 (s, 1H), 7.85 (s, 1H), 7.71 (t, J=4.83 Hz, 1H), 7.45-7.51 (m, 2H), 7.41 (t, J=7.40 Hz, 2H), 7.30-7.35 (m, 1H), 7.13-7.19 (m, 1H), 6.94 (d, J=8.16 Hz, 1H), 6.91 (d, J=7.78 Hz, 1H), 5.11 (s, 2H), 3.13-3.25 (m, 1H), 2.65-2.88 (m, 3H), 2.56 (br d, J=9.41 Hz, 1H), 2.24 (s, 3H), 1.95 (br s, 1H), 1.77-1.90 (m, 1H).

[0630] Example 107: 2-(5-cyclopropylpyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method A. [ka]

[0631] Intermediate 52a: 2-(5-bromopyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 6, step i, intermediate 7c (0.1 g, 369.92 μmol, 1 eq) and 2,5-dibromopyrimidine (263.99 mg, 1.11 mmol, 3 eq) were mixed in dioxane (20 mL) and CuI (35.23 mg, 184.96 μmol, 0.5 eq), K3PO4 (196.31 mg, 924.81 μmol, 2.5 eq), and DMEDA (16.30 mg, 184.96 μmol, 0.5 eq) were added all at once under N2 at 25°C. The mixture was stirred at 25°C for 5 minutes, then heated to 110°C and stirred for 12 hours. The reaction mixture was filtered and the filtrate was concentrated. This residue was purified by silica gel chromatography (PE:SiO=15 / 1~1 / 1) to obtain intermediate 52a (0.08 g, 187.22 μmol, 50.61% yield) as a yellow solid.

[0632] 1 1H NMR: (CDCl 3, 400 MHz) H) δ 8.88 (s, 2H), 7.61 (s, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.75-6.58 (m, 2H), 3.73 (s, 3H), 3.07-2.85 (m, 2H), 2.75-2.65 (m, 1H), 2.61-2.57 (m, 2H), 2.23 (s, 3H), 2.08-2.05 (m, 1H), 1.81-1.76 (m, 1H).

[0633] Example 107: 2-(5-cyclopropylpyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 6, step ii, a mixture of intermediate 52a (0.2 g, 468.06 μmol, 1 eq) and cyclopropylboronic acid (78.25 mg, 0.94 mmol, 5 eq) in dioxane (20 mL) was added all at once under N2 at 25 °C to a mixture of Pd(dppf)Cl2 (17.12 mg, 23.40 μmol, 0.05 eq) and K2CO3 (77.61 mg, 0.56 mmol, 3.0 eq). The mixture was stirred at 25 °C for 5 minutes, then heated to 110 °C and stirred for 12 hours. The reaction mixture was filtered, and the filtrate was concentrated. The residue was pre-purified by column chromatography, and subsequently prepared by HPLC to obtain Example 107 (0.053 g, 136.44 μmol, 29.15% yield) as a white solid.

[0634] 1 H-NMR (400 MHz, CDCl3) δ 8.77 (s, 2H), 7.84 (s, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.73 (dd, J = 2.4, 8.4 Hz, 1H), 3.78 (s, 3H), 3.11 (m, 1H), 2.80-2.52 (m, 4H), 2.28 (s, 3H), 2.09-2.06 (m, 1H), 1.93-1.84 (m, 3H), 1.14-1.14 (m, 2H), 1.00-0.97 (m, 2H).

[0635] Example 108: 2-(5-cyclopropylpyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method A. [ka]

[0636] Intermediate 52b: 2-(5-bromopyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 6, step i, intermediate 52b was prepared using intermediate 7a (0.5 g, 1.97 mmol) and 2,5-dibromopyridine (558.87 mg, 2.36 mmol) as starting materials, in the same manner as described for intermediate 52a, and intermediate 52b (0.7 g, 1.71 mmol, 86.78% yield) was obtained as a pale yellow solid.

[0637] 1 H NMR (400MHz, CDCl3) δ 8.72 (s, 1H), 7.98 (dd, J = 8.4, 2.0 Hz, 1H), 7.80-7.66 (m, 2H), 7.18-6.95 (m, 3H), 3.14 (m, 1H), 3.06-2.93 (m, 1H), 2.86-2.76 (m, 1H), 2.76-2.61 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.14 (m, H), 1.96-1.78 (m, 1H).

[0638] Example 108: 2-(5-cyclopropylpyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one In accordance with Scheme 6, step ii, Example 108 was prepared using intermediate 52b (0.2, 487.44 μmol) and cyclopropylboronic acid (209.35 mg, 2.44 mmol) as starting materials, following the same method as described for intermediate Example 107, to obtain Example 108 (0.08 g, 213.20 μmol, 43.74% yield) as a white solid.

[0639] 1H-NMR (400 MHz, CDCl3) δ 8.63 (s, 2H), 7.69 (s, 1H), 7.17-6.97 (m, 3H), 3.14 (m, 1H), 3.00 (m, 1H), 2.86-2.76 (m, 1H), 2.75-2.59 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.12 (m, 1H), 2.03-1.95 (m, 1H), 1.98 (m, 1H), 1.93-1.77 (m, 1H), 1.25-1.10 (m, 2H), 0.88 (m, 2H).

[0640] Example 109: 2-(5-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method A. [ka]

[0641] Intermediate 52c: 2-(5-bromopyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 6, step i, intermediate 52c was prepared in the same manner as described for intermediate 52a, and intermediate 52c (1.2 g, 2.92 mmol, 74.20% yield) was obtained as a pale yellow solid using intermediate 7a (1 g, 3.93 mmol) and 2,5-dibromopyrimidine (1.12 g, 4.72 mmol) as starting materials.

[0642] 1 H NMR (400MHz, CDCl3) δ 8.95 (s, 2H), 7.69 (s, 1H), 7.14-6.99 (m, 3H), 3.26-3.09 (m, 1H), 3.00 (m, 1H), 2.86-2.75 (m, 1H), 2.75-2.59 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.12 (m, 1H), 1.93-1.79 (m, 1H).

[0643] Example 109: 2-(5-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one In accordance with Scheme 6, step ii, Example 109 was prepared in the same manner as described for intermediate Example 107, and using intermediate 52c (200.48 mg, 487.44 μmol) and cyclopropylboronic acid (209.35 mg, 2.44 mmol) as starting materials, Example 109 (0.124 g, 329.59 μmol, 67.62% yield) was obtained as a pale yellow solid.

[0644] 1 H-NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.71 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.46 (dd, J = 2.0, 8.4 Hz, 1H), 7.13-7.07 (m, 1H), 7.06-7.00 (m, 2H), 3.19-3.09 (m, 1H), 3.04-2.92 (m, 1H), 2.85-2.76 (m, 1H), 2.74-2.58 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.15-2.10 (m, 1H), 2.03-1.94 (m, 1H), 1.93-1.81 (m, 1H), 1.13-1.05 (m, 2H), 0.82-0.74 (m, 2H).

[0645] Example 110: 2-(5-cyclopropylpyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method A. [ka]

[0646] Intermediate 52d: 2-(5-bromopyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 6, step i, intermediate 52d was prepared in the same manner as described for intermediate 52a, and intermediate 52d (1.2 g, 2.81 mmol, 76.09% yield) was obtained as a yellow solid using intermediate 7b (1 g, 3.70 mmol) and 2,5-dibromopyridine (2.63 g, 11.10 mmol) as starting materials.

[0647] 1 H NMR (DMSO-d6, 400MHz) δ 8.76 (m, 1H), 8.28 (dd, J = 2.0, 8.4 Hz, 1H), 7.95 (m, 1H), 7.63 (br s, 1H), 7.18 (t, J = 8.0 Hz, 1H), 7.00-6.85 (m, 2H), 3.79 (s, 3H), 3.17 (m, 1H), 2.87-2.65 (m, 4H), 2.25 (m, 1H), 2.18 (s, 3H), 1.88-1.81 (m, 1H).

[0648] Example 110: 2-(5-cyclopropylpyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one In accordance with Scheme 6, Step II, Example 110 was prepared in the same manner as described for Intermediate Example 107, and Example 110 (0.09 g, 232.27 μmol, 33.01% yield) was obtained as a yellow solid using intermediate 52d (0.3 g, 703.72 μmol) and cyclopropylboronic acid (302.24 mg, 3.52 mmol) as starting materials.

[0649] 1H-NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.83 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 3.79 (s, 3H), 3.15 (m, 1H), 2.87-2.65 (m, 4H), 2.34 (m, 1H), 2.18 (s, 3H), 2.05 (m, 1H), 1.85 (m, 1H), 1.08-1.05 (m, 2H), 0.83 (m, 2H).

[0650] Example 111: 6-(3-methoxy-2-methylphenyl)-2-(5-(pyrrolidine-1-yl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0651] According to Scheme 6, step iii, a mixture of Example 43 (180 mg, 470.17 μmol, 1 eq) and pyrrolidine (66.88 mg, 940.33 μmol, 78.49 μL, 2 eqs) in dioxane (5 mL) was stirred at 20 °C under N2 with RUPHOS pre-catalyst (36.52 mg, 47.02 μmol, 0.1 eq) and Cs2CO3 (382.97 mg, 1.18 mmol, 2.5 eq). This mixture was stirred at 100 °C for 12 hours. This mixture was poured into H2O (15 mL). The aqueous phase was filtered and extracted with CH2Cl2 (20 mL × 2). The combined organic phase was concentrated under vacuum and combined with the filter cake, and the crude product was purified by preparative HPLC. Example 111 (0.98 mg, 2.21 μmol, 0.5% yield) was obtained as a white solid.

[0652] 1H-NMR (400 MHz, DMSO-d6) δ 8.18 (s, 2H), 7.78 (s, 1H), 7.14-7.21 (m, 1H), 6.89 (d, J=7.91 Hz, 1H), 6.85 (d, J=8.03 Hz, 1H), 3.78 (s, 3H), 3.27-3.34 (m, 4H), 3.13-3.22 (m, 1H), 2.65-2.83 (m, 3H), 2.52-2.58 (m, 1H), 2.18 (s, 3H), 1.91-2.05 (m, 5H), 1.77-1.89 (m, 1H).

[0653] Example 112: (6-(3-methoxy-2-methylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0654] In accordance with Scheme 6, step iii, Example 112 was prepared using Example 43 (150 mg, 391.81 μmol) and morpholine (68.27 mg, 783.61 μmol, 68.96 μL) as starting materials, following the same method as described in, for example, 111, to obtain Example 112 (37.27 mg, 83.31 μmol, 21.26% yield) as a white solid.

[0655] 1 H-NMR (400 MHz, DMSO-d6) δ 8.61 (s, 2H), 7.81 (s, 1H), 7.14-7.22 (m, 1H), 6.88 (dd, J=7.91, 16.81 Hz, 2H), 3.75-3.82 (m, 7H), 3.34 (br s, 4H), 3.12-3.22 (m, 1H), 2.76-2.86 (m, 1H), 2.63-2.75 (m, 2H), 2.56 (br s, 1H), 2.18 (s, 3H), 1.94 (br s, 1H), 1.77-1.90 (m, 1H).

[0656] Example 113: 6-(3-methoxy-2-methylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0657] In accordance with Scheme 6, step iii, Example 113 was prepared using intermediate 52d (0.2 g, 469.15 μmol) and morpholine (81.74 mg, 938.29 μmol, 82.57 μL) as starting materials, following the same method as described in, for example, 111, to obtain Example 113 (0.092 g, 212.71 μmol, 45.34% yield) as a yellow solid.

[0658] 1 H-NMR (400 MHz, CDCl3) δ 8.45 (br s, 1H), 8.03 (br s, 1H), 7.81 (br s, 1H), 7.59 (br s, 1H), 7.23 (br t, J = 7.8 Hz, 1H), 6.95-6.81 (m, 2H), 3.94 (m, 4H), 3.88 (s, 3H), 3.37 (br s, 4H), 3.25 (br s, 1H), 2.99 (m, 1H), 2.92-2.82 (m, 1H), 2.81-2.65 (m, 3H), 2.27 (s, 3H), 2.16 (br s, 1H), 1.93-1.90 (m, 1H).

[0659] Example 114: 6-(2,4-dimethylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0660] In accordance with Scheme 6, step iii, Example 114 was prepared using intermediate 52b (0.15 g, 365.58 μmol) and morpholine (63.70 mg, 731.16 μmol, 64.34 μL) as starting materials, following the same method as described in, for example, 111, to obtain Example 114 (0.029 g, 66.14 μmol, 18.09% yield) as a pale yellow solid.

[0661] 1 H-NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 8.02-7.90 (m, 1H), 7.78 (s, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.13-7.01 (m, 3H), 3.97-3.87 (m, 4H), 3.40-3.29 (m, 4H), 3.20-3.08 (m, 1H), 2.98 (m, 1H), 2.89-2.78 (m, 1H), 2.71 (m, 2H), 2.35 (s, 3H), 2.33 (s, 3H), 2.15-2.10 (m, 1H), 1.95-1.82 (m, 1H).

[0662] Example 115: 6-(2,4-dimethylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0663] In accordance with Scheme 6, step iii, Example 115 was prepared using intermediate 52c (0.15 g, 364.70 μmol) and morpholine (63.55 mg, 729.40 μmol, 64.19 μL) as starting materials, following the same method as described in, for example, 111, to obtain Example 115 (0.053 g, 126.95 μmol, 34.81% yield) as a pale yellow solid.

[0664] 1H-NMR (400 MHz, CDCl3) δ 8.48 (s, 2H), 7.69 (s, 1H), 7.13-6.99 (m, 3H), 3.97-3.88 (m, 4H), 3.38-3.28 (m, 4H), 3.20-3.08 (m, 1H), 2.99 (m, 1H), 2.88-2.75 (m, 1H), 2.70 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.17-2.05 (m, 1H), 1.95-1.80 (m, 1H).

[0665] Example 116: 2-(5-(azetidine-1-yl)pyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method B. [ka]

[0666] In accordance with Scheme 6, step iii, Example 116 was prepared using intermediate 52c (0.15, 364.70 μmol) and azetidine (136.48 mg, 1.46 mmol, 161.32 μL) as starting materials, following the same method as described in, for example, 111, to obtain Example 116 (0.004 g, 9.81 μmol, 2.69% yield) as a pale yellow solid.

[0667] 1 H-NMR (400 MHz, CDCl3) δ 8.01 (s, 2H), 7.65 (s, 1H), 7.17-6.99 (m, 3H), 4.08 (t, J = 7.2 Hz, 4H), 3.12 (m, 1H), 3.02-2.95 (m, 1H), 2.83-2.75 (m, 1H), 2.70-2.62 (m, 2H), 2.62-2.52 (m, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.12-2.06 (m, 1H), 1.92-1.80 (m, 1H).

[0668] Example 117: N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide was prepared according to Scheme 6, Method B. [ka]

[0669] According to Scheme 6, step iii, to a mixture of intermediate 52c (0.1 g, 243.13 μmol, 1 eq) and acetamide (28.72 mg, 486.27 μmol, 2 eq) in dioxane, (1S,2S)-N,N-dimethylcyclohexane-1,2-diamine (6.92 mg, 48.63 μmol, 0.2 eq), CuI (9.24 mg, 48.63 μmol, 0.2 eq), and K3PO4 (129 mg, 607.82 μmol, 2.5 eq) were added all at once under N2 at 25°C. The mixture was stirred at 25°C for 5 minutes, then heated to 100°C and stirred for 12 hours. The reaction mixture was filtered and the filtrate was concentrated. The residue was further purified by preparative HPLC to obtain Example 117 (0.021 g, 53.92 μmol, 22.18% yield) as a white solid.

[0670] 1 H-NMR (400 MHz, CDCl3) δ 8.93 (s, 2H), 8.58 (s, 1H), 7.66 (s, 1H), 7.03-6.97 (m, 3H), 3.12-3.06 (m, 1H), 2.98-2.88 (m, 1H), 2.82-2.72 (m, 1H), 2.72-2.61 (m, 2H), 2.29 (s, 3H), 2.25 (s, 3H), 2.15 (s, 3H), 2.12-2.05 (m, 1H), 1.88-1.82 (m, 1H).

[0671] Example 118: 6-(3-methoxy-2-methylphenyl)-2-(5-(2-methoxyethoxy)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method C. [ka]

[0672] According to Scheme 6, step iv, Cs2CO2 was added to the solution of compound Example 45 (150 mg, 411.64 μmol, 1 eq) in DMA (3 mL). 3( 268.24 mg (823.28 μmol, 2 eq) and 1-bromo-2-methoxyethane (572.14 mg, 4.12 mmol, 386.58 μL, 10 eq) were added. The mixture was stirred at 20°C for 12 hours. HCl (6N) was added to the mixture to adjust the pH to 7. The mixture was filtered. The filtrate was concentrated to obtain the crude product. The crude product was purified by preparative HPLC to obtain Example 118 (79.75 mg, 186.50 μmol, 45.31% yield) as a white solid.

[0673] 1 H-NMR (400 MHz, CDCl3) δ 8.75 (s, 2H), 7.70 (s, 1H), 7.12 (br d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 6.72 (m, d, J = 8.4 Hz, 1H), 3.80 (s, 3H), 3.17-2.96 (m, 2H), 2.87-2.76 (m, 1H), 2.71-2.65 (m, 2H), 2.43 (s, 3H), 2.31 (s, 3H), 2.15-2.11 (m, 1H), 1.90-1.85 (m,1H).

[0674] Example 119: 2-(5-(2-hydroxyethoxy)pyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method C. [ka]

[0675] In accordance with Scheme 6, step iv, Example 119 was prepared using Example 45 (150 mg, 411.64 μmol) and 2-bromoethane-1-ol (514.40 mg, 4.12 mmol) as starting materials, following the same method as described in, for example, 118, to obtain Example 119 (45.04 mg, 107.73 μmol, 26.17% yield) as a white solid.

[0676] 1 H-NMR (400 MHz, CDCl3) δ 8.46 (s, 2H), 7.59 (s, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.73-6.64 (m, 2H), 3.93 (s, 3H), 3.73 (s, 3H), 3.04-2.97 (m, 2H), 2.71-2.46 (m, 3H), 2.23 (s, 3H), 2.08 (m, 1H), 1.80 (m, 1H).

[0677] Example 120: 6-(3-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 7. [ka]

[0678] Intermediate 53: 6-(3-bromo-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 2, step viii, intermediate 15b (2 g, 5.68 mmol, 1 eq) and 1,3-dibromo-2-methylbenzene (1.42 g, 5.68 mmol, 72.57 μL, 1 eq) were mixed in dioxane (30 mL) and H2O (2 mL) at 25 °C under N2, to which Pd(dppf)Cl2 (207.76 mg, 283.93 μmol, 0.05 eq) and Na2CO3 (1.81 g, 17.04 mmol, 3 eq) were added all at once. This mixture was stirred at 90 °C for 12 hours. The residue was poured into ice water (w / w=1 / 1) (50 mL). The aqueous phase was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and vacuum concentrated to obtain intermediate 53 (1.4 g, 3.54 mmol, 62.37% yield) as a yellow solid.

[0679] 1 H NMR (CDCl3, 400 MHz) δ 8.92 (d, J = 4.8 Hz, 2H), 7.75 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.40 (t, J = 4.8 Hz, 1H), 7.11-7.06 (m, 2H), 6.24 (s, 1H), 3.00 (t, J = 9.6 Hz, 2H), 2.64 (t, J = 9.6 Hz, 2H), 2.42 (s, 3H).

[0680] Intermediate 54: 6-(3-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-7,8-dihydrophthalazine-1(2H)-one Following Scheme 7, step i, intermediate 53 (0.2 g, 506.01 μmol, 1 eq) and tributyl(1-ethoxyvinyl) stanane (365.49 mg, 1.01 mmol, 341.58 μL, 2 eq) were mixed in dioxane (20 mL) and Pd(PPh3)2Cl2 (17.76 mg, 25.30 μmol, 0.05 eq) was added all at once under N2 at 25 °C. The mixture was stirred at 100 °C for 3 hours. HCl (3 M; 20 mL) was added to the reaction mixture and stirred at 25 °C for 30 minutes, followed by vacuum concentration. The residue was purified by silica gel chromatography (PE / HCl=0 / 1) to obtain intermediate 54 (0.15 g, crude) as a yellow solid.

[0681] 1 H NMR (DMSO-d6, 400 MHz) δ 9.01 (d, J = 4.8 Hz, 2H), 7.99 (s, 1H), 7.65-7.75 (m, 1H), 7.36 (s, 1H), 6.42 (s, 1H), 2.78-2.87 (m, 2H), 2.60-2.68 (m, 2H), 2.56 (s, 3H), 2.36 (s, 3H).

[0682] Example 120: 6-(3-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 7, step ii, a mixture of intermediate 54 (150.00 mg, 418.53 μmol, 1 eq) and ammonium formate (131.96 mg, 2.09 mmol, 5 eq) in EtOH (30 mL) was added to Pd / C (0.3 g, 5% purity) under N2. This mixture was stirred at 25°C for 16 hours. This mixture was filtered and concentrated under reduced pressure, and the resulting residue was purified by PREP-HPLC to obtain Example 120 (4 mg, 10.86 μmol, 2.60% yield) as a white solid.

[0683] (DMSO-d6) δ 9.02 (d, J = 4.8 Hz, 2H), 7.85 (s, 1H), 7.71 (br t, J = 4.8 Hz, 1H), 7.48 (m, 2H), 7.29-7.36 (m, 1H), 3.27 (m, 1H), 2.65-2.95 (m, 4H), 2.54 (s, 3H), 2.35 (s, 3H), 1.88-2.03 (m, 2H).

[0684] Example 121: 6-(2,4-dimethylphenyl)-2-(pyridin-2-yl)-2,5,6,7-tetrahydro-1H-cyclopenta[d]-pyridazine-1-one was prepared according to Scheme 3. [ka]

[0685] Intermediate 19: 3-(2,4-dimethylphenyl)cyclopenta n-1-one Following Scheme 3, step i, KOH (4.10 g, 73.08 mmol) was added to a mixture of Rh(COD)Cl2 (180.17 mg, 0.37 mmol) in dioxane (20 mL) and H2O (4 mL). The resulting mixture was stirred at 20°C under N2 for 0.5 hours. Next, cyclopenta-2-en-1-one (6.00 g, 73.08 mmol) and a solution of (2,4-dimethylphenyl)boronic acid (21.92 g, 146.16 mmol) in dioxane (20 mL) were added dropwise to the resulting mixture at 20°C. The resulting mixture was stirred at 20°C for 1.5 hours. The desired product was confirmed by LC-MS. The reaction mixture was diluted with 200 mL of ethyl acetate and washed with water (60 mL x 3). Next, the organic phase was dried over anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by column chromatography using silica gel (PE:SiO = 20:1). Intermediate 19 (11.00 g, 80% yield) was obtained as a yellow liquid.

[0686] 1H NMR (CDCl3; 400MHz) δ 7.17- 7.10(m, 1H), 7.07-7.02 (m, 2H), 3.67-3.54 (m, 1H), 2.70-2.60 (m, 1H), 2.55-2.45(m, 1H), 2.43-2.39 (m, 1H), 2.381 (s, 3H), 2.37-2.35 (m,1H), 2.34 (s, 3H ), 2.31-2.26 (m,1H), 2.10-1.96 (m,1H).

[0687] Intermediate 20: 2-Chloro-4-(2,4-dimethylphenyl)cyclopenta-1-ene-1-carbaldehyde Following Scheme 3, step ii, POCl3 (13.03 g, 84.99 mmol, 7.9 mL) was added to a mixture of DMF (7.76 g, 106.24 mmol, 8.2 mL) in CH2Cl2 (100 mL) at -20°C. The mixture was then stirred at 0°C for 1 hour. Next, a solution of intermediate 19 (10.00 g, 53.12 mmol) in CH2Cl2 (20 mL) was added to this mixture at -20°C. The reaction mixture was stirred at 0°C for 2 hours. Next, the reaction mixture was stirred at 25°C for 12 hours. The completion of the reaction was confirmed by LC-MS. The reaction mixture was rapidly cooled to 0°C with water (100 mL). Next, the mixture was extracted with CH2Cl2 (100 mL x 3). The combined organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated. The residue was purified by silica gel chromatography (PE:SiO = 10:1). 2-Chloro-4-(2,4-dimethylphenyl)cyclopenta-1-ene-1-carbaldehyde 20 and its regioisomer 2-Chloro-5-(2,4-dimethylphenyl)cyclopenta-1-ene-1-carbaldehyde 20' (3.00 g, 24% yield) were obtained as a yellow oily substance and used in the next step.

[0688] Intermediate 21: Ethyl 4-(2,4-dimethylphenyl)-2-formylcyclopenta-1-ene-1-carboxylate A mixture of intermediates 20 and 20' (1.5 g, 6.39 mmol) and Et3N (1.29 g, 12.78 mmol, 1.77 mL) in EtOH (40 mL) was mixed with Pd(dppf)Cl2 (467.61 mg, 0.64 mmol) at 25 °C under N2 protection. This suspension was degassed under vacuum and purged with CO for several hours. The mixture was stirred at 120 °C for 12 hours under CO (3 MPa). Next, the reaction mixture was concentrated. A crude mixture of intermediate 21 and its regioisomer 21' (1.5 g, crude) was obtained as a black solid and used in the next step.

[0689] Example 121: 6-(2,4-dimethylphenyl)-2-(pyridin-2-yl)-2,5,6,7-tetrahydro-1H-cyclopenta[d]-pyridazine-1-one Intermediate 21 and its regioisomer 21' (3.00 g, 11.02 mmol) and 2-pyridylhydrazine (2.41 g, 16.53 mmol HCl) were mixed in toluene (100 mL) and TsOH (1.90 g, 11.02 mmol) was added under N2 conditions at 25 °C. This mixture was stirred at 120 °C for 48 hours. The reaction mixture was concentrated. The residue was purified by silica gel chromatography (PE / SiO=3:1), and the resulting crude product was further purified by preparative HPLC. Example 121 (180 mg, 5% yield) was obtained as a yellow oily substance.

[0690] 1 H-NMR (400 MHz, CDCl3) δ 8.75 (s, 1H), 8.10-7.96 (m, 2H), 7.90-7.80 (m, 1H), 7.55-7.45 (m,1H), 7.13 (d, J = 7.6Hz, 1H), 7.07-6.99 (m, 2H), 4.10-3.99 (m, 1H), 3.50-3.37 (m, 2H), 3.06-3.01 (m, 2H), 2.38 (s, 3H), 2.33 (s, 3H).

[0691] Example 122: 7-(2,4-dimethylphenyl)-3-(pyridine-2-yl)-5,6,7,8-tetrahydroquinazoline-4(3H)-one was prepared according to Scheme 4. [ka]

[0692] Intermediate 31: 2',4'-dimethyl-5,6-dihydro-[1,1'-biphenyl]-3(4H)-one According to Scheme 4, step i, a solution of cyclohex-2-en-1-one (3.50 g, 36.41 mmol, 1.00 eq), 1-indo-2,4-dimethylbenzene (10.81 g, 46.60 mmol, 1.28 eq), Na2CO3 (6.04 g, 72.82 mmol, 2.00 eq), Pd(PPh3)2Cl2 (2.56 g, 3.64 mmol, 0.10 eq), and XPhos (2.08 g, 4.37 mmol, 0.12 eq) in DMSO (100.00 mL) was stirred at 100°C for 2 hours under an N2 atmosphere. The desired product was confirmed by LC-MS, and the reaction was terminated. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with H2O (40 mL x 3). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (PE:SiO=5:1). Intermediate 31 (1.60 g, 7.99 mmol, 22% yield) was obtained as a brown liquid.

[0693] 1 H NMR (CDCl3; 400MHz) δ 7.19-6.94 (m, 3H), 5.92-5.90 (m, 1H), 2.53-2.50 (m, 2H), 2.45-2.40 (m, 2H), 2.26 (s, 3H), 2.21 (s, 3H), 2.09-2.05 (m, 2H).

[0694] Intermediate 33: Ethyl 2',4'-dimethyl-5-oxo-2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-carboxylate Following Scheme 4, step iii, LDA (2M, 8.99mL, 1.50eq) was added dropwise to a solution of intermediate 31 (2.40g, 11.98 mmol, 1.00eq) in THF (60.00mL) at -78°C. The resulting mixture was stirred at -78°C for 1 hour. To this reaction mixture, ethyl cyanoethyl (1.66g, 16.77 mmol, 1.65mL, 1.40eq) was added dropwise at -78°C and stirred for 4 hours. The reaction mixture was quenched with aqueous NH4Cl solution (20mL), extracted with ethyl acetate, washed with 100mL of H2O, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (PE:HCl=5:1). Intermediate 33 (2.10 g, 7.71 mmol, 64.37% yield) was obtained as a yellow oily substance.

[0695] 1 H NMR (CDCl3; 400MHz) δ 7.04-7.04 (m, 3H), 6.09-6.05 (m, 1H), 4.25-4.3 (m, 2H), 2.73-2.53 (m, 4H), 2.35 (s, 3H), 2.30 (s, 3H) 1.66-1.60 (m, 3H).

[0696] Intermediate 34: Ethyl 4-(2,4-dimethylphenyl)-2-oxocyclohexane-1-carboxylate Following Scheme 4, step ii, a solution of intermediate 33 (1.40 g, 5.14 mmol, 1.00 eq) in MeOH (20.00 mL) was added to Pd / C (500 mg, 10% purity) under an N2 atmosphere. This suspension was degassed under vacuum and purged with H2 for several hours. The mixture was stirred under H2 (50 psi) at 20°C for 16 hours. The reaction mixture was filtered and concentrated under reduced pressure. The crude product was purified by flash silica gel chromatography (PE:HCl = 10:1). Intermediate 34 (500.00 mg, 1.82 mmol, 35.40% yield) was obtained as a yellow oily substance.

[0697] Intermediate 35: 7-(2,4-dimethylphenyl)-5,6,7,8-tetrahydroquinazoline-4(3H)-one Following Scheme 4, step iv, a mixture of intermediate 34 (200 mg, 729.00 μmol, 1.00 eq), K2CO3 (403.02 mg, 2.92 mmol, 4.00 eq), and formidoamide (113.84 mg, 1.09 mmol, 1.50 eq) in EtOH (8.00 mL) was stirred at 90°C for 3 hours. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate (100 mL). This solution was washed with H2O (40 mL x 3). The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. Intermediate 35 (120.00 mg, 471.83 μmol, 65% yield) was obtained as a pale yellow solid.

[0698] 1 H NMR (DMSO-d6; 400MHz) δ 12.30 (s, 1H), 7.99 (s, 1H), 7.17-7.11 (m, 1H), 6.97-6.99 (m, 1H), 3.11-3.08 (m, 1H), 2.68-2.39 (m, 4H), 2.28 (s, 3H), 2.24 (s, 3H), 1.86-1.84(m, 2H), 1.75-1.1.72 (m, 2H).

[0699] Example 122: 7-(2,4-dimethylphenyl)-3-(pyridine-2-yl)-5,6,7,8-tetrahydroquinazoline-4(3H)-one Following Scheme 4, step v, a mixture of intermediate 35 (100.00 mg, 393.19 μmol, 1.00 eq), 2-bromopyridine (80.76 mg, 511.15 μmol, 1.30 eq), CuI (7.49 mg, 39.32 μmol, 0.10 eq), 1,10-penanthroline (14.17 mg, 78.64 μmol, 0.20 eq), and KOH (44.12 mg, 786.38 μmol, 2.00 eq) in DMF (4.00 mL) was stirred at 100 °C for 12 hours under an N2 atmosphere. The reaction mixture was diluted with 100 mL of ethyl acetate and washed with water (30 mL x 3). The organic phase was dried over Na2SO4 and evaporated under vacuum. The crude product was purified by preparative HPLC (with formic acid added). Example 122 (45.00 mg, 135.78 μmol, 34.53% yield) was obtained as a yellow solid.

[0700] 1 H-NMR (400 MHz, DMSO-d6) δ 8.66-8.65 (m, 1H), 8.48 (s, 1H), 8.06-8.04 (m, 1H), 7.77-7.75 (m, 1H), 7.59-7.55 (m, 1H), 7.18-7.15 (m, 1H), 7.02-6.99 (m, 1H), 3.16-3.14 (m, 1H), 2.75-2.66 (m, 4H), 2.30 (s, 3H), 2.25 (s, 3H),1.94-1.921 (m, 1H), 1.83-1.81 (m, 2H).

[0701] Example 124: 6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0702] To the mixture of Example 92 (50.0 mg, 130 μmol, 1.00 eq) in DCM (2.00 mL), MnO2 (113 mg, 1.30 mmol, 10.0 eq) was added at 25°C. This mixture was stirred at 25°C for 23 hours. The reaction product was filtered and concentrated. The residue was purified by column chromatography (SiO2, PE / Depositphotos = 1 / 1 to 0:1, Rf = 0.48) to obtain Example 124 (37.0 mg, 94.7 μmol) as a green solid.

[0703] 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J=4.8 Hz, 2H), 7.71 (s, 1H), 7.51 (d, J=8.2 Hz, 1H), 7.42 (t, J=4.8 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 7.18 (d, J=3.4 Hz, 1H), 6.99 (d, J=7.4 Hz, 1H), 6.50 (d, J=3.4 Hz, 1H), 3.48 - 3.33 (m, 2H), 3.07 - 2.87 (m, 3H), 2.80 - 2.66 (m, 1H), 2.37 - 2.28 (m, 1H), 2.14 - 2.06 (m, 1H), 1.11 - 1.02 (m, 4H).

[0704] Example 125: 2-(5-cyclopropylpyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 6, Method A. [ka]

[0705] Intermediate 52e: 2-(5-bromopyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 6, step i, intermediate 52e was prepared in the same manner as described for intermediate 52a, and intermediate 52e (0.5 g, 1.01 mmol, 54.41% yield) was obtained as a red solid using intermediate 7b (500 mg, 1.85 mmol) and 2,5-dibromopyridine (527.98 mg, 2.22 mmol) as starting materials. m / z(M+H) + = 427.0, 429.0.

[0706] Example 125: 2-(5-cyclopropylpyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one In accordance with Scheme 6, step ii, Example 125 was prepared using intermediate 52e (180 mg, 421.26 μmol) and cyclopropylboronic acid (72.37 mg, 842.51 μmol) as starting materials, following the same method as described in, for example, 107, and Example 125 (14.61 mg, 37.35 μmol, 8.87% yield) was obtained as a light pink solid.

[0707] 1 H-NMR (400 MHz, DMSO-d6) δ 8.76 (s, 2H), 7.83 (s, 1H), 7.18 (t, J=7.97 Hz, 1H), 6.90 (d, J=7.65 Hz, 1H), 6.86 (d, J=8.16 Hz, 1H), 3.79 (s, 3H), 3.13-3.24 (m, 1H), 2.64-2.85 (m, 3H), 2.57 (br s, 1H), 2.18 (s, 3H), 2.04-2.12 (m, 1H), 1.94 (br s, 1H), 1.78-1.90 (m, 1H), 1.08-1.18 (m, 2H), 0.90-1.01 (m, 2H).

[0708] Example 126: 2-(5-bromopyrimidine-2-yl)-6-(3-cyclopropoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one was prepared according to Scheme 1, Method B. [ka]

[0709] Intermediate 6f: 5-(3-cyclopropoxy-2-methylphenyl)-3-methoxy-4,5,6,7-tetrahydroisobenzo-furan-1(3H)-one Following Scheme 1, steps i-v, intermediate 6f was prepared using 1-bromo-3-cyclopropoxy-2-methylbenzene as the starting material, similar to intermediate 6a in Example 1, and obtained as a colorless oil with a total yield of 6%. m / z(M+H) + = 315.3.

[0710] Intermediate 7d: 6-(3-cyclopropoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Following Scheme 1, step vii, intermediate 7b was prepared using intermediate 6f (1.77 g, 5.60 mmol) as the starting material, similar to intermediate 7a in Example 6, and intermediate 7d (1.52 g, 4.56 mmol, 81.5% yield) was obtained as a bright yellow solid.

[0711] 1 H NMR (400 MHz, DMSO-d6) δ 10.73 (br s, 1H), 7.56 (s, 1H), 7.22 - 7.11 (m, 2H), 6.84 (d, J=7.4 Hz, 1H), 3.77 - 3.70 (m, 1H), 3.22 - 3.11 (m, 1H), 2.99 - 2.88 (m, 1H), 2.81 - 2.71 (m, 1H), 2.71 - 2.54 (m, 2H), 2.18 (s, 3H), 2.15 - 2.08 (m, 1H), 1.92 - 1.80 (m, 1H), 0.82 - 0.77 (m, 4H).

[0712] Example 126: 2-(5-bromopyrimidine-2-yl)-6-(3-cyclopropoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one According to Scheme 1, step viii, Example 126 was prepared according to Example 6 using intermediate 7d (1.00 g, 3.00 mmol) and 2,5-dibromopyrimidine (856 mg, 3.60 mmol) as starting materials, and Example 126 (0.74 g, 1.52 mmol, 50.7% yield) was obtained as a red solid.

[0713] 1 H NMR (400 MHz, CDCl3) δ 8.95 (s, 2H), 7.69 (s, 1H), 7.24 - 7.14 (m, 2H), 6.85 (d, J=7.6 Hz, 1H), 3.77 - 3.70 (m, 1H), 3.20 (br s, 1H), 3.00 (br d, J=16.3 Hz, 1H), 2.86 - 2.78 (m, 1H), 2.70 (br dd, J=9.2, 16.8 Hz, 2H), 2.20 - 2.18 (m, 3H), 2.13 (br s, 1H), 1.94 - 1.85 (m, 1H), 0.82 - 0.77 (m, 4H).

[0714] Example 127: N-(2-(6-(3-cyclopropoxy-2-methylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide was prepared according to Scheme 6, Method B. [ka]

[0715] According to Scheme 6, step iii, Example 127 was prepared according to Example 117, using Example 126 (0.85 g, 1.88 mmol) and acetamide (222 mg, 3.75 mmol) as starting materials, and Example 127 (242 mg, 558.61 μmol, 29.79% yield) was obtained as a bright yellow solid.

[0716] 1H NMR (400 MHz, CDCl3) δ 9.07 - 9.00 (m, 1H), 8.97 (s, 2H), 7.76 (s, 1H), 7.24 - 7.15 (m, 2H), 6.86 (br d, J=7.4 Hz, 1H), 3.75 (br s, 1H), 3.25 (br s, 1H), 3.00 (br d, J=19.4 Hz, 1H), 2.92 - 2.82 (m, 1H), 2.82 - 2.64 (m, 2H), 2.20 (s, 6H), 2.17 - 2.13 (m, 1H), 1.93 (br d, J=7.2 Hz, 1H), 0.80 (br s, 4H).

[0717] Example 128: (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one and Example 129: (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0718] By separating the enantiomers constituting racemic Example 104 (483 mg) by prepared SFC, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 128 (188 mg, 39%) was obtained with a 100% excess of enantiomers, and (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 129 (199 mg, 41%) was obtained with a 99.9% excess of enantiomers, both as white solids.

[0719] Example 128: 1H-NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.4 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.28 - 7.15 (m, 2H), 6.85 (d, J = 7.6 Hz, 1H), 3.75 (tt, J = 6.0, 3.2 Hz, 1H), 3.25-3.17 (m, 1H), 3.05 - 2.95 (m, 1H), 2.87 - 2.76 (m, 1H), 2.75 - 2.60 (m, 2H), 2.20 - 2.10 (m, 1H), 1.95 - 1.83 (m, 1H), 0.85 - 0.75 (m, 4H).

[0720] Example 129: 1 H-NMR (400 MHz, CDCl3) δ 8.94 (d, J = 4.4 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.25 - 7.15 (m, 2H), 6.86 (d, J = 7.6 Hz, 1H), 3.75 (tt, J = 6.0, 3.2 Hz, 1H), 3.25-3.17 (m, 1H), 3.05 - 2.95 (m, 1H), 2.83 - 2.76 (m, 1H), 2.75 - 2.60 (m, 2H), 2.20 - 2.07 (m, 1H), 1.95 - 1.82 (m, 1H), 0.85 - 0.75 (m, 4H).

[0721] Example 130: (-)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one and Example 131: (+)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0722] By separating the enantiomers constituting racemic Example 91 (505 mg) by preparation SFC, (-)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 130 (187 mg, 37%) was obtained with an enantiomer excess of 99.6%, and (+)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 131 (187 mg, 37%) was obtained with an enantiomer excess of 99.9%, both as white solids.

[0723] Example 130: 1 H-NMR (400 MHz, CDCl3) δ 8.93 (d, J = 4.4 Hz, 2H), 7.70 (s, 1H), 7.42 (t, J = 4.8 Hz, 1H), 7.26 - 7.23 (m, 2H), 6.92 - 6.87 (m, 1H), 3.83 (tt, J = 6.0, 3.2 Hz, 1H), 3.59 - 3.49 (m, 1H), 3.05 - 2.92 (m, 2H), 2.76 - 2.58 (m, 2H), 2.23 - 2.14 (m, 1H), 1.99 - 1.85 (m, 1H), 0.90 - 0.83 (m, 4H).

[0724] Example 131: 1 H-NMR (400 MHz, CDCl3) δ 8.93 (d, J=4.8 Hz, 2H), 7.70 (s, 1H), 7.45 - 7.39 (m, 1H), 7.26 - 7.23 (m, 2H), 6.94 - 6.86 (m, 1H), 3.83 (tt, 0.92 - 0.79 (m, 4H).

[0725] Example 132: (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one and Example 133: (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0726] By separating the enantiomers constituting racemic Example 93 (488 mg) by preparation SFC, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 132 (232 mg, 48%) was obtained with a 100% excess of enantiomers, and (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one Example 133 (210 mg, 43%) was also obtained with a 100% excess of enantiomers, both as white solids.

[0727] Example 132: 1 H-NMR (400 MHz, CDCl3) δ 8.74 (s, 2H), 7.68 (s, 1H), 7.25 - 7.15 (m, 2H), 6.85 (d, J = 6.4 Hz, 1H), 3.74 (tt, J = 6.0, 3.2 Hz, 1H), 3.26-3.17 (m, 1H), 3.05 - 2.95 (m, 1H), 2.85 - 2.77 (m, 1H), 2.75 - 2.60 (m, 2H), 2.43 (s, 3H), 2.18 - 2.10 (m, 1H), 1.95 - 1.83 (m, 1H), 0.85 - 0.78 (m, 4H).

[0728] Example 133: 1H-NMR (400 MHz, CDCl3) δ 8.74 (s, 2H), 7.68 (s, 1H), 7.23 - 7.15 (m, 2H), 6.85 (d, J = 6.4 Hz, 1H), 3.74 (tt, J = 6.0, 3.2 Hz, 1H), 3.25-3.16 (m, 1H), 3.05 - 2.95 (m, 1H), 2.85 - 2.77 (m, 1H), 2.75 - 2.60 (m, 2H), 2.43 (s, 3H), 2.18 - 2.07 (m, 1H), 1.95 - 1.83 (m, 1H), 0.83 - 0.76 (m, 4H).

[0729] Example 134: (-)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one and Example 135: (+)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one [ka]

[0730] By separating the enantiomers constituting racemic Examp...

Claims

1. Compound of formula (I): 【Chemistry 1】 (Here, G is N or CR ７ Selected from, E is N or CR ８ Selected from, However, if only one of G or E is N, Y is CR ９ And, R １ 、 R ２ 、 R ３ 、 R ４ 、 R ５ 、 R ６ 、 R ７ 、 R ８ and R ９ each is hydrogen, n is an integer selected from 0 or 1. Ar １ is a complex aryl that may be substituted by any other, Ar ２ (This is an aryl or complex aryl that may be substituted by any other element.) Alternatively, pharmaceutically acceptable salts and solvates thereof, or their optical isomers, racemates, diastereoisomers, enantiomers, or tautomers.

2. - Ar １ The following: 【Chemistry 2】 (Here, m is the number of substituents A on the ring, and is an integer equal to 0, 1, 2, 3, or 4.) Represents a complex aryl selected from and / or - Ar ２ The following: 【Transformation 3】 (Here, p is the number of substituents B on the ring, and is an integer equal to 0, 1, 2, 3, 4, or 5.) Represents an aryl or complex aryl selected from (Here, A and B may be the same or different, and each may independently be hydrogen, halogen, -CN, and -NO) ２ -OH, -NH ２ , -CF ３ , and also, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C ３ -C ８ ) Cycloalkenyl, -(C １ -C ６ ) cyanoalkyl, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-aryl, -(C １ -C ６ ) Alkylene-heterocyclic ring, aryl, heteroaryl, heterocyclic ring, -OR １３ , - (C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ (C ２ -C ６ ) Alkilen-OR １４ , - (C ２ -C ６ ) Alkenylene-OR １３ , - (C ２ -C ６ ) Alkinylene-OR １３ , -NR １３ R １４ , - (C １ -C ６ ) Alkilen-NR １３ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ R １４ , -NR １３ -(C ２ -C ６ ) alkylene - NR １４ R １５ , -(C ２ -C ６ ) alkenylene - NR １３ R １４ , -(C ２ -C ６ ) alkynylene - NR １３ R １４ , -SR １３ , -(C １ -C ６ ) alkylene - SR １３ , -O-(C ２ -C ６ ) alkylene - SR １３ , -NR １３ -(C ２ -C ６ ) alkylene - SR １４ , -S(=O)-R １３ , -(C １ -C ６ ) alkylene - S(=O)-R １３ , -O-(C １ -C ６ ) alkylene - S(=O)-R １３ , -NR １３ -(C １ -C ６ ) alkylene - S(=O)-R １４ , -S(=O) ２ -R １３ , -(C １ -C ６ ) alkylene - S(=O) ２ -R １３ , -O-(C １ -C ６ ) alkylene - S(=O) ２ -R １３ , -NR １３ -(C １ -C ６ ) alkylene - S(=O) ２ -R １４ , -S(=O) ２ NR １３ R １４ , -(C １ -C ６ ) Alkylene-S (=O) ２ NR １３ R １４ , -O-(C １ -C ６ ) Alkylene-S (=O) ２ NR １３ R １４ , -NR １３ - (C １ -C ６ ) Alkylene-S (=O) ２ NR １４ R １５ , -NR １３ -S (=O) ２ R １４ , - (C １ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -S (=O) ２ R １５ , -C(=O)-NR １３ R １４ , - (C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -O-(C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-NR １４ R １５ , -NR １３ C(=O)-R １４ , - (C １ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ C(=O)-R １５ , -C(=O)-R １３ , - (C １ -C ６ ) Alkylene-C(=O)-R １３ , -O-(C １ -C ６ ) Alkylene-C(=O)-R １３ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-R １４ , -C(=O)-OR １３ , - (C １ -C ６ ) Alkylene-C(=O)-OR １３ , -O-(C １ -C ６ ) Alkylene-C(=O)-OR １３ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-OR １４ , -OC(=O)-R １３ , - (C １ -C ６ ) Alkylene-OC(=O)-R １３ , -O-(C ２ -C ６ ) Alkylene-OC(=O)-R １３ , -NR １３ - (C ２ -C ６ ) Alkylene-OC(=O)-R １４ , -NR １３ -C(=O)-NR １４ R １５ , - (C １ -C ６ ) Alkilen-NR １３ -C(=O)-NR １４ R １５ , -O-(C ２ -C ６ ) Alkilen-NR １３ -C(=O)-NR １４ R １５ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -C(=O)-NR １５ R １６ , -NR １３ -C (=O) -OR １４ , - (C １ -C ６ ) Alkilen-NR １３ -C (=O) -OR １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ -C (=O) -OR １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -C (=O) -OR １５ , -OC(=O)-NR １３ R １４ , - (C １ -C ６ ) Alkylene-O-C(=O)-NR １３ R １４ , -O-(C ２ -C ６ ) Alkylene-O-C(=O)-NR １３ R １４ , -NR １３ - (C ２ -C ６ ) Alkylene-O-C(=O)-NR １４ R １５ , -C(=O)-(C １ -C ６ ) Alkilen-NR １３ R １４ , - (C １ -C ６ ) Alkylene-C(=O)-(C １ -C ６ ) Alkilen-NR １３ R １４ , -C(=O)-(C １ -C ６ ) Alkilen-OR １３ , - (C １ -C ６ ) Alkylene-C(=O)-(C １ -C ６ ) Alkilen-OR １３ , -NR １３ -C(=S)-NR １４ R １５ , - (C １ -C ６ ) Alkilen-NR １３ -C(=S)-NR １４ R １５ , -NR １３ -C (=NR １４ ) - NR １５ R １６又は - (C １ -C ６ ) Alkilen-NR １３ -C (=NR １４ ) - NR １５ R １６ A radical which may be substituted by any of the group selected from the group, Selected from the group consisting of; Here, R １３ , R １４ , R １５ and R １６ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) Haloalkyl, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) cyanoalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heteroaryl, aryl, heterocyclic, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-heterocyclic rings, and -(C １ -C ６ ) Selected from alkylene-aryl, Here, R is chosen at will. １３ , R １４ , R １５ or R １６ Any two radicals selected from may together form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally halogen, cyano, nitro, hydroxyl, amino, -(C) １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, Here, any two radicals A and any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, heterocycle, aryl, or heteroaryl ring, where each ring is optionally a halogen, -CN, hydroxyl, amino, or -(C) １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. The compound according to claim 1.

3. Formula (II): 【Chemistry 4】 (Here - Ar １ The following: 【Transformation 5】 Represents a complex aryl selected from, Here, - m is the number of substituents A on the ring, and is an integer equal to 0, 1, 2, 3, or 4. - A may be the same or different, and each can be independently hydrogen, halogen, -CN, and -CF ３ -OH, -NH ２ , and also - (C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-heterogeneous ring, heterogeneous ring, aryl, heteroaryl, -OR １３ , - (C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ (C ２ -C ６ ) Alkilen-OR １４ , -NR １３ R １４ , - (C １ -C ６ ) Alkilen-NR １３ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ R １５ , -SR １３ , - (C １ -C ６ ) Alkilen-SR １３ , -O-(C ２ -C ６ ) Alkilen-SR １３ , -NR １３ - (C ２ -C ６ ) Alkilen-SR １４ , -S (=O) -R １３ , -S (=O) ２ -R １３ , -S (=O) ２ NR １３ R １４ , - (C １ -C ６ ) Alkylene-S (=O) ２ NR １３ R １４ , -NR １３ -S (=O) ２ R １４ , - (C １ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -S (=O) ２ R １５ , -C(=O)-NR １３ R １４ , - (C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -O-(C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-NR １４ R １５ , -NR １３ C(=O)-R １４ , - (C １ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ C(=O)-R １５ , -C(=O)-R １３ , -C(=O)-OR １３ , - (C １ -C ６ ) Alkylene-C(=O)-OR １３ , -O-(C １ -C ６ ) Alkylene-C(=O)-OR １３ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-OR １４ , -OC(=O)-R １３ , - (C １ -C ６ ) Alkylene-OC(=O)-R １３ , -O-(C ２ -C ６ ) Alkylene-OC(=O)-R １３ , -NR １３ - (C ２ -C ６ ) Alkylene-OC(=O)-R １４ , or -NR １３ -C (=O) -OR １４ A group consisting of radicals that may be optionally substituted, selected from the group, - Here, R １３ , R １４ and R １５ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heteroaryl, aryl, heterocyclic, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-heterocyclic rings, and -(C １ -C ６ ) Selected from alkylene-aryl, - Here, optionally R on substituent A １３ , R １４ or R １５ Any two radicals selected from may together form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally a halogen, -CN, or -NO ２ -OH, -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Here, any two radicals A may form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring with the intervening atom, where each ring may optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, and / or - Ar ２ The following: 【Transformation 6】 Represents an aryl or complex aryl selected from, Here - p is the number of substituents B on the ring, and is an integer equal to 0, 1, 2, 3, 4, or 5. - B may be the same or different, and each can be independently hydrogen, halogen, -CN, and -CF ３ , and also, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) alkylene-heterocycle, -(C1-C6)alkylene-aryl, heterocycle, -OR １３ , - (C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ (C ２ -C ６ ) Alkilen-OR １４ , -NR １３ R １４ , - (C １ -C ６ ) Alkilen-NR １３ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ R １５ , -SR １３ , - (C １ -C ６ ) Alkilen-SR １３ , -O-(C ２ -C ６ ) Alkilen-SR １３ , -NR １３ - (C ２ -C ６ ) Alkilen-SR １４ , -S (=O) -R １３ , - (C １ -C ６ ) Alkilen-S(=O)-R １３ , -O-(C １ -C ６ ) Alkilen-S(=O)-R １３ , -NR １３ - (C １ -C ６ ) Alkilen-S(=O)-R １４ , -S (=O) ２ -R １３ , - (C １ -C ６ ) Alkylene-S (=O) ２ -R １３ , -O-(C １ -C ６ ) Alkylene-S (=O) ２ -R １３ , -NR １３ - (C １ -C ６ ) Alkylene-S (=O) ２ -R １４ , -S (=O) ２ NR １３ R １４ , - (C １ -C ６ ) Alkylene-S (=O) ２ NR １３ R １４ , -O-(C １ -C ６ ) Alkylene-S (=O) ２ NR １３ R １４ , -NR １３ - (C １ -C ６ ) Alkylene-S (=O) ２ NR １４ R １５ , -NR １３ -S (=O) ２ R １４ , - (C １ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ -S (=O) ２ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -S (=O) ２ R １５ , -C(=O)-NR １３ R １４ , - (C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -O-(C １ -C ６ ) Alkylene-C(=O)-NR １３ R １４ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-NR １４ R １５ , -NR １３ C(=O)-R １４ , - (C １ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ C(=O)-R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ C(=O)-R １５ , -C(=O)-R １３ , - (C １ -C ６ ) Alkylene-C(=O)-R １３ , -O-(C １ -C ６ ) Alkylene-C(=O)-R １３ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-R １４ , -C(=O)-OR １３ , - (C １ -C ６ ) Alkylene-C(=O)-OR １３ , -O-(C １ -C ６ ) Alkylene-C(=O)-OR １３ , -NR １３ - (C １ -C ６ ) Alkylene-C(=O)-OR １４ , -OC(=O)-R １３ , - (C １ -C ６ ) Alkylene-OC(=O)-R １３ , -O-(C ２ -C ６ ) Alkylene-OC(=O)-R １３ , -NR １３ - (C ２ -C ６ ) Alkylene-OC(=O)-R １４ , - (C １ -C ６ ) Alkilen-NR １３ -C(=O)-NR １４ R １５ , -NR １３ -C (=O) -OR １４ , - (C １ -C ６ ) Alkilen-NR １３ -C (=O) -OR １４ , -O-(C ２ -C ６ ) Alkilen-NR １３ -C (=O) -OR １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ -C (=O) -OR １５ , -OC(=O)-NR １３ R １４ , - (C １ -C ６ ) Alkylene-O-C(=O)-NR １３ R １４ , -O-(C ２ -C ６ ) Alkylene-O-C(=O)-NR １３ R １４ , -NR １３ - (C ２ -C ６ ) Alkylene-O-C(=O)-NR １４ R １５ , -C(=O)-(C １ -C ６ ) Alkilen-NR １３ R １４ , -C(=O)-(C １ -C ６ ) Alkilen-OR １３ A radical selected from the group which may be substituted by any of the following, - Here, R １３ , R １４ and R １５ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) Haloalkyl, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) cyanoalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heteroaryl, aryl, heterocyclic, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-heterocyclic rings, and -(C １ -C ６ ) Selected from alkylene-aryl, - Here, optionally, R on substituent B １３ , R １４ or R １５ Any two radicals selected from may together form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally a halogen, -CN, or -NO ２ -OH, -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring may optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. The compound according to claim 1 or 2.

4. - A may be the same or different, and each can be independently hydrogen, halogen, -CN, and -CF ３ , -OH, and -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-heterogenetic ring, heterogenetic ring, -OR １３ , - (C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ (C ２ -C ６ ) Alkilen-OR １４ , -O(C ２ -C ６ ) Alkilen-NR １３ R １４ , -NR １３ - (C ２ -C ６ ) Alkilen-NR １４ R １５ , -NR １３ R １４ , - (C １ -C ６ ) Alkilen-NR １３ R １４ , -NR １３ C(=O)-R １４ , -C(=O)-NR １３ R １４ , S (=O) ２ NR １３ R １４ or -NR １３ -S (=O) ２ R １４ A radical selected from the group which may be substituted by any of the following, - Here, R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ３ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heterocyclic, and -(C １ -C ６ ) Selected from alkylene-heterogenes, - Here, optionally, radical R on substituent A １３ and R １４ These may together form a 3-6 membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ They may be further substituted by 1 to 5 radicals independently selected from and / or - B may be the same or different, and each independently is hydrogen, halogen, -CF ３ , -CN, and -(C １ -C ６ ), alkyl, -(C １ -C ６ ), haloalkyl, -(C ３ -C ７ ), cycloalkyl, -(C １ -C ６ ), alkylene-(C ３ -C ７ ), cycloalkyl, -(C １ -C ６ ), alkylene-aryl, heterocyclic ring, -OR １３ , -(C １ -C ６ ), alkylene-OR １３ , -O-(C ２ -C ６ ), alkylene-OR １３ 、 -NR １３ (C ２ -C ６ ), alkylene-OR １４ , -NR １３ R １４ , -SR １３ , -(C １ -C ６ ), alkylene-SR １３ , -S(=O)-R １３ , -S(=O) ２ -R １３ , -NR １３ C(=O)-R １４ , -C(=O)-NR １３ R １４ , -C(=O)-OR １３ , -OC(=O)-R １３ , -C(=O)-(C １ -C ６ ), alkylene-OR １３ or -C(=O)-R １３ and is selected from the group consisting of optionally substituted radicals; - Here, R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heteroaryl, aryl, heterocyclic, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-heterocyclic rings, and -(C １ -C ６ ) Selected from alkylene-aryl, - Here, optionally, R on substituent B １３ and R １４ Any two radicals selected from may together form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally a halogen, CN, -OH, -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ They may be further substituted by 1 to 5 radicals independently selected from and / or - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring may optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. The compound according to claim 2 or 3.

5. Formula (III): 【Transformation 7】 (Here - A may be the same or different and each independently is hydrogen, halogen, -CN, -CF ３ , and -OH, -(C １ -C ６ ), alkyl, -(C １ -C ６ ), haloalkyl, -(C ３ -C ７ ), cycloalkyl, -(C １ -C ６ ), alkylene-(C ３ -C ７ ), cycloalkyl, -(C １ -C ６ ), alkylene - heterocyclic ring, heterocyclic ring, -OR １３ , -(C １ -C ６ ), alkylene - OR １３ , -O-(C ２ -C ６ ), alkylene - OR １３ 、 -NR １３ (C ２ -C ６ ), alkylene - OR １４ , -O(C ２ -C ６ ), alkylene - NR １３ R １４ , -NR １３ -(C ２ -C ６ ), alkylene - NR １４ R １５ , -NR １３ R １４ , -(C １ -C ６ ), alkylene - NR １３ R １４ , -NR １３ C(=O)-R １４ , -C(=O)-NR １３ R １４ , S(=O) ２ NR １３ R １４ or -NR １３ -S(=O) ２ R １４ is selected from the group consisting of optionally substituted radicals, - Here, R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ３ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heterocyclic, and -(C １ -C ６ ) Selected from alkylene-heterogenes, - Here, optionally, radical R on substituent A １３ and R １４ These may together form a 3-6 membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Here, any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ They may be further substituted by 1 to 5 radicals independently selected from and / or - B may be the same or different, and each can be independently hydrogen, halogen, and -CF ３ , -CN, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-aryl, heterocycle, -OR １３ , - (C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ (C ２ -C ６ ) Alkilen-OR １４ , -NR １３ R １４ , -SR １３ , - (C １ -C ６ ) Alkilen-SR １３ , -S (=O) -R １３ , -S (=O) ２ -R １３ , -NR １３ C(=O)-R １４ , -C(=O)-NR １３ R １４ , -C(=O)-OR １３ , -OC(=O)-R １３ , -C(=O)-(C １ -C ６ ) Alkilen-OR １３ or -C(=O)-R １３ A radical selected from the group which may be substituted by any of the following, - Here, R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heteroaryl, aryl, heterocyclic, -(C １ -C ６ ) Alkylene-complex aryl, -(C １ -C ６ ) Alkylene-heterocyclic rings, and -(C １ -C ６ ) Selected from alkylene-aryl, - Here, optionally, R on substituent B １３ and R １４ Any two radicals selected from may together form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally a halogen, CN, -OH, -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ They may be further substituted by 1 to 5 radicals independently selected from and / or - Here, any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring may optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. The compound according to claim 2.

6. - A may be the same or different, and each can be independently hydrogen, halogen, -CN, and -CF ３ , -OH, and -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-heterogenetic ring, heterogenetic ring, -O-(C １ -C ６ ) alkyl, O-(C １ -C ３ ) Alkyl-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkilen-OR １３ , -O-(C ２ -C ６ ) Alkilen-OR １３ 、 -NR １３ R １４ , - (C １ -C ６ ) Alkilen-NR １３ R １４ or -NR １３ C(=O)-R １４ A group consisting of radicals that may be optionally substituted by a radical selected from the group; - R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ３ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, or -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Selected from cycloalkyl, - Optionally, radical R on substituent A １３ and R １４ These may together form a 3- to 6-membered carbon ring or heteroring, where each ring can optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Any two radicals A may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring may optionally be a halogen, -CN, or -(C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. 、 The compound according to any one of claims 2 to 5.

7. - B may be the same or different, and each can be independently hydrogen, halogen, and -CF ３ , and also, -(C １ -C ６ ) alkyl, -(C １ -C ６ ) Haloalkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, heterocyclic, -O-(C １ -C ６ ) alkyl, -O-(C ３ -C ７ ) Cycloalkyl, -O-(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkilen-OR １３ , -O-(C １ -C ６ ) alkylene-aryl, -O-(C ２ -C ６ ) Alkylene-O-(C １ -C ６ ) alkyl, -NR １３ R １４ or -C(=O)-R １３ A radical selected from the group which may be substituted by any of the following, - R １３ and R １４ Each of these may be independently substituted with hydrogen, or optionally with (C １ -C ６ ) alkyl, -(C ３ -C ７ ) Cycloalkyl, -(C １ -C ６ ) Alkylene-(C ３ -C ７ ) Selected from cycloalkyl, - Optionally, radical R on substituent B １３ and R １４ These may together form a 3-6 membered carbon ring, hetero ring, aryl ring, or heteroaryl ring, where each ring can optionally be a halogen, -CN, -OH, or -NH ２ , - (C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ -C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above, - Any two radicals B may, together with the intervening atom, form a 3- to 10-membered carbon ring, hetero ring, aryl or heteroaryl ring, where each ring is optionally a halogen, -CN, or -(C １ -C ６ ) alkyl 、 -O-(C １ -C ６ ) alkyl, and -N-((C １ C ６ )alkyl) ２ It may be further substituted by 1 to 5 radicals independently selected from the above. The compound according to any one of claims 2 to 6.

8. - Ar １ The following: 【Transformation 8】 Represents a complex aryl selected from, and / or, - Ar ２ The following: 【Chemistry 9】 Represents an aryl or complex aryl selected from, The compound according to any one of claims 2 to 7.

9. 6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, 6-(3-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, (-)-6-(2,4-dimethylphenyl)-2-pyridine-2-yl-5,6,7,8-tetrahydro-2H-phthalazine-1-one, 6-(2,4-dimethylphenyl)-2-(5-chloropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(4-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(3-chloropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(6-fluoropyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-fluoropyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(6-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-methoxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(6-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(3-methylpyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)picolinonitrile, 6-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile, 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl) isonicotinonitrile, 2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)nicotinonitrile, 6-(2,4-dimethylphenyl)-2-(5-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-hydroxypyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(methoxymethyl)pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridine-3-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyrimidine-5-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(thiazol-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(thiazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(1-methyl-1H-imidazol-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4,6-dimethylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(4-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-hydroxypyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-(hydroxymethyl)pyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(4-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-methoxypyrazine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-hydroxypyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(4-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridine-4-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-chloropyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-methoxypyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-fluoropyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(trifluoromethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(4-methoxy-5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-(morpholinomethyl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(dimethylamino)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(pyridine-2-yl)-6-(o-tolyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(1-hydroxyethyl)phenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-4-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-3-methylphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-4-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-3-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-(trifluoromethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-fluoro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-5-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methoxy-5-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-methyl-5-(pyrrolidine-1-yl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-fluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,5-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,3-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(methoxymethyl)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(cyclopentyloxy)phenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-methoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(1,5-dimethyl-1H-indazol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-Mesityl-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,6-difluoro-3-methoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one 6-(2-methoxyphenyl)-2-(pyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(dimethylamino)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(5-methoxy-2,4-dimethylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-chloro-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(4-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(3-methoxypropoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-ethoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(cyclopropylmethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-isopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(2-methoxyethoxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-(benzyloxy)-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-(pyrrolidine-1-yl)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-methoxy-2-methylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyridine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(5-morpholinopyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-(azetidine-1-yl)pyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, 6-(3-methoxy-2-methylphenyl)-2-(5-(2-methoxyethoxy)pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (2-(5-(2-hydroxyethoxy)-pyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(3-acetyl-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 6-(2,4-dimethylphenyl)-2-(pyridine-2-yl)-2,5,6,7-tetrahydro-1H-cyclopenta[d]-pyridazine-1-one, 7-(2,4-dimethylphenyl)-3-(pyridine-2-yl)-5,6,7,8-tetrahydroquinazoline-4(3H)-one, 6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-cyclopropylpyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(3-cyclopropoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, N-(2-(6-(3-cyclopropoxy-2-methylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2-chloro-3-cyclopropoxyphenyl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(3-cyclopropoxy-2-methylphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (+)-6-(2-chloro-3-methoxyphenyl)-2-(5-methylpyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (+)-N-(2-(6-(2,4-dimethylphenyl)-1-oxo-5,6,7,8-tetrahydrophthalazine-2(1H)-yl)pyrimidine-5-yl)acetamide, (+)-6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, (-)-6-(1-cyclopropyl-1H-indol-4-yl)-2-(pyrimidine-2-yl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(5-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyridine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyridine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, 2-(5-bromopyrimidine-2-yl)-6-(3-methoxy-2-methylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one, and 2-(5-bromo-4-methoxypyrimidine-2-yl)-6-(2,4-dimethylphenyl)-5,6,7,8-tetrahydrophthalazine-1(2H)-one A compound according to claim 1, selected from, or a pharmaceutically acceptable salt and solvate thereof, or an optical isomer, racemate, diastereoisomer, enantiomer, or tautomer thereof.

10. The compound according to any one of claims 1 to 9, in the form of a racemic mixture or in the form of one or both of the individual optical isomers.

11. A pharmaceutical composition comprising a therapeutically effective amount of the compound described in any one of claims 1 to 10 and a pharmaceutically acceptable excipient.

12. The pharmaceutical composition according to claim 11 for reducing, inhibiting, or negatively regulating the activity of the metabotropic glutamate receptor mGluR7.

13. The pharmaceutical composition according to claim 11 for the prevention or treatment of disorders associated with glutamate deficiency in mammals.

14. Anxiety disorders, agoraphobia, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder Disorders: PTSD, social phobias, other phobias, mood disorders, bipolar disorder (I & II), cyclothymic disorder, depression, dysthymic disorder, major depressive disorder, drug-induced mood disorders, mood disorders due to systemic conditions, mania, manic-depressive illness, seasonal affective disorder, muscle spasms and disorders associated with muscle spasms, tremors, epilepsy, convulsions, migraines, mild cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neurodegenerative disorders, schizophrenia, delusional disorder, schizoaffective disorder, schizophrenia-like disorder, drug-induced mental disorders, mental disorders, personality disorders, obsessive-compulsive personality disorder, schizoid, schizoid disorder, borderline personality disorder Personality disorders, anxiety-avoidant personality disorder, childhood disorders, attention deficit hyperactivity disorder, intellectual disability, Down syndrome, tic disorder, autism spectrum disorder, Rett syndrome, fragile X syndrome, autism, hearing impairment, inner ear disorders, disorders, functional impairments or conditions, sensorineural hearing loss, age-related hearing loss (presbycusis), Meniere's disease, sudden hearing loss, noise-induced hearing loss, drug-induced hearing loss, latent hearing loss, cisplatin-induced hearing loss, aminoglycoside-induced hearing loss, otitis media, toxic hearing loss, autoimmune inner ear disorders, acute tinnitus, chronic tinnitus, central auditory processing disorder, and vestibular disorders, gastrointestinal disorders, diarrhea, constipation, gastroesophageal reflux disease (GERD), lower esophageal sphincter disease or disorder, gastrointestinal motility disorders, colitis, Crohn's disease, or irritable bowel syndrome (IBS).A pharmaceutical composition according to claim 11 or 13 for the prevention or treatment of disorders selected from: syndrome (IBS), pain disorders, acute pain, chronic pain, severe pain, intractable pain, inflammatory pain, postoperative pain, headache, cancer pain, neuropathic pain, post-traumatic pain, and visceral pain, cognitive impairment and mood disorders associated with the aforementioned disorders, eye diseases, ocular hypertension, glaucoma, normal-tension glaucoma, neurodegenerative conditions of the retina and optic nerve, retinal dystrophy, age-related macular degeneration, eye conditions, conjunctivitis, keratoconjunctivitis sicca, and vernal keratoconjunctivitis, inflammation and / or neurodegeneration, traumatic brain injury, seizures, stroke, ischemia, spinal cord injury, cerebral hypoxia, cerebral hemorrhage or intracranial hematoma.

15. Anxiety disorders, agoraphobia, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder Disorders: PTSD, social phobias, other phobias, mood disorders, bipolar disorder (I & II), cyclothymic disorder, depression, dysthymic disorder, major depressive disorder, drug-induced mood disorders, mood disorders due to systemic conditions, mania, manic-depressive illness, seasonal affective disorder, muscle spasms and disorders associated with muscle spasms, tremors, epilepsy, convulsions, migraines, mild cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neurodegenerative disorders, schizophrenia, delusional disorder, schizoaffective disorder, schizophrenia-like disorder, drug-induced mental disorders, mental disorders, personality disorders, obsessive-compulsive personality disorder, schizoid, schizoid disorder, borderline personality disorder Personality disorders, anxiety-avoidant personality disorder, childhood disorders, attention deficit hyperactivity disorder, intellectual disability, Down syndrome, tic disorder, autism spectrum disorder, Rett syndrome, fragile X syndrome, autism, hearing impairment, inner ear disorders, disorders, functional impairments, medical conditions, sensorineural hearing loss, age-related hearing loss (presbycusis), Meniere's disease, sudden hearing loss, noise-induced hearing loss, drug-induced hearing loss, latent hearing loss, cisplatin-induced hearing loss, aminoglycoside-induced hearing loss, otitis media, toxic hearing loss, autoimmune inner ear disorders, acute tinnitus, chronic tinnitus, central auditory processing disorder, and vestibular disorders, gastrointestinal disorders, diarrhea, constipation, gastroesophageal reflux disease (GERD), lower esophageal sphincter disease or disorder, gastrointestinal motility disorders, colitis, Crohn's disease, or irritable bowel syndrome (IBS).Use of a compound according to any one of claims 1 to 10 for the manufacture of a medicament for the prevention or treatment of a disorder selected from: syndrome (IBS), pain disorder, acute pain, chronic pain, severe pain, intractable pain, inflammatory pain, postoperative pain, headache, cancer pain, neuropathic pain, post-traumatic pain, and visceral pain, cognitive impairment and mood disorders associated with one or more of the aforementioned disorders, eye diseases, ocular hypertension, glaucoma, normal-tension glaucoma, neurodegenerative conditions of the retina and optic nerve, retinal dystrophy, age-related macular degeneration, eye conditions, conjunctivitis, keratoconjunctivitis sicca, and vernal keratoconjunctivitis, inflammation and / or neurodegeneration, traumatic brain injury, seizure, stroke, ischemia, spinal cord injury, cerebral hypoxia, cerebral hemorrhage or intracranial hematoma.

16. Use of the compound according to any one of claims 1 to 10 for the manufacture of a pharmaceutical for radiolabeled tracers for imaging the metabolically regulated glutamate receptor mGluR7 in mammals.

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