Homopiperazinyl and homopiperidinyl quinazolin-4(3H)-one derivatives with diverse activities against pain

Abstract

The present invention relates to homopiperazinyl and homopiperidinyl quinazolin-4(3H)-one derivatives that have dual pharmacological activity on both the α2δ subunit of voltage-gated calcium channels and the sigma-1 (σ1) receptor, processes for preparing such compounds, pharmaceutical compositions containing them, and their use in therapy, particularly for the treatment of pain.

Description

[Technical field]

[0001] The present invention relates to a voltage-dependent calcium channel α 2 The present invention relates to compounds having dual pharmacological activity on both the δ subunit and the sigma-1 (σ1) receptor, more particularly to homopiperazinyl and homopiperidinyl quinazolin-4(3H)-one derivatives having this pharmacological activity, processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in therapy, particularly for the treatment of pain. [Background technology]

[0002] Proper management of pain is a significant challenge, as currently available treatments often provide only marginal improvement and many patients remain unrelieved (Turk DC, Wilson HD, Cahana A. Lancet; 2011, 377, 2226-2235). Pain affects a significant portion of the population, with an estimated prevalence of 20%, and its incidence, especially in the case of chronic pain, is increasing due to the aging of the population. Furthermore, pain is clearly associated with comorbidities such as depression, anxiety, and insomnia, which result in significant productivity loss and socioeconomic burden (Goldberg DS, McGee SJ, BMC Public Health, 2011, 11, 770). Existing pain therapies include nonsteroidal anti-inflammatory drugs (NSAIDs), opioid agonists, calcium channel blockers, and antidepressants, which are far from optimal in terms of their safety rates. All of these exhibit limited efficacy and various side effects that preclude their use, especially in the chronic phase.

[0003] Voltage-gated calcium channels (VGCCs) are required for many important functions in the body. Different subtypes of voltage-gated calcium channels have been described (Zamponi et al., Pharmacol. Rev. 2015, 67, 821-70). VGCCs are made up of different subunits, namely α 1(Ca v α 1 ), β(Ca v β)α 2 δ(Ca v α 2 δ), and γ(Ca v γ) interactions. 1 The subunits are the important porous-forming units of the channel complex and transport Ca 2+ Conduction and Ca 2+ It is involved in the generation of influx. 2 The δ, β, and γ subunits are auxiliary, but they do not mediate the α 1 They are of great importance for the regulation of channels, since they increase the expression and modulate the function of the subunits, resulting in functional diversity in different cell types. Based on their physiological and pharmacological properties, VGCCs are known to mediate the channel-forming Ca V Depending on the α subunit, low-voltage-activated T-type (Ca v 3.1 Ca v 3.2, and Ca v 3.3), and high-voltage-activated L-type (Ca v 1.1~Ca v 1.4), N-type (Ca v 2.2), P / Q type (Ca v 2.1), and R type (Ca v VGCCs can be subdivided into three subclasses: 1) neurotransmitter release, 2) membrane depolarization and hyperpolarization, 3) enzyme activation and deactivation, and 4) gene regulation. All five of these subclasses are found in the central and peripheral nervous system. The regulation of intracellular calcium through activation of these VGCCs plays an essential role in 1) neurotransmitter release, 2) membrane depolarization and hyperpolarization, 3) enzyme activation and deactivation, and 4) gene regulation (Perret and Luo, Neurotherapeutics 2009, 6, 679-92; Zamponi et al., 2015 (supra); Neumaier et al., Prog. Neurobiol. 2015, 129, 1-36). A large amount of data clearly implicates VGCCs in mediating various pathologies, including pain processing. Drugs that interact with different calcium channel subtypes and subunits have been developed. Current therapeutic agents include the L-type Ca channel, which is widely used in the treatment of hypertension.v 1.2 Drugs that target calcium channels, especially 1,4-dihydropyridines. T-type (Ca v 3) The N-type (Ca channel is the target of ethosuximide, a drug widely used in absence epilepsy. v 2.2) Ziconotide, a peptide blocker of calcium channels, has been approved for the treatment of intractable pain (Perret and Luo, 2009 (supra); Vink and Alewood, Br. J. Pharmacol. 2012, 167, 970-89).

[0004] Ca v 1 and Ca v The 2 subfamily is a complementary α-agonist that is a valuable therapeutic target for gabapentinoid drugs in certain epilepsy and chronic neuropathic pain. 2 Contains δ subunits. To date, there are four known α 2 There are δ subunits, each encoded by a unique gene, and all have splice variants. 2 The δ proteins are encoded by a single messenger RNA, are post-translationally cleaved, and subsequently linked by disulfide bonds. 2 Four genes encoding the δ subunits have now been cloned. 2 Delta-1 was first cloned from skeletal muscle and shows a fairly widespread distribution. 2 Delta-2 and Alpha 2 The delta-3 subunit was cloned from brain. 2 Delta-4 is mostly non-neuronal. Human alpha 2 The δ-4 protein sequence is 2 δ-1, α 2 δ-2 and α 2 It shares 30%, 32%, and 61% identity with the δ-3 subunit. 2 The gene structure of the δ subunit is similar. 2The δ subunit exhibits several splice variants (Davies et al., Trends Pharmacol. Sci. 2007, 28, 220-8.; Dolphin AC, Nat Rev Neurosci. 2012, 13, 542-55, Biochim. Biophys. Acta 2013, 1828, 1541-9).

[0005] Ca v α 2 The delta-1 subunit may play an important role in the development of neuropathic pain (Perret and Luo, 2009, supra; Vink and Alewood, 2012, supra). Biochemical data show that significant Ca2+ upregulation in the spinal dorsal horn and DRG after nerve injury is associated with the development of neuropathic pain. v α 2 Ca instead of δ-2 v α 2 We have shown that injury-induced DRG Ca upregulation in presynaptic terminals leads to upregulation of the δ-1 subunit. v α 2 Blocking axonal transport of the δ-1 subunit reduced tactile allodynia in nerve-injured animals, which was associated with elevated DRG Ca v α 2 These results suggest that the delta-1 subunit contributes to neuropathic allodynia.

[0006] Ca v α 2 δ-1 subunit (and Ca v α 2 δ-2 subunit, but Ca v α 2 δ-3 and Ca v α 2 The δ-4 subunit (except for the δ-4 subunit) is the binding site for gabapentin, which has anti-allodynic / hyperalgesic properties in patients and animal models. v α 2Delta-1 expression correlates with neuropathic pain, its development and maintenance, and various calcium channels are known to contribute to synaptic neurotransmission in the spinal cord and DRG neuron excitability, so injury-induced Ca v α 2 Upregulation of the δ-1 subunit may contribute to the initiation and maintenance of neuropathic pain by altering the properties and / or distribution of VGCCs in subpopulations of DRG neurons and their central terminals, thus regulating excitability and / or synaptic neuroplasticity in the dorsal horn. v α 2 Intrathecal antisense oligonucleotides against the delta-1 subunit inhibited nerve injury-induced Ca v α 2 Blocking the upregulation of delta-1 can prevent the development of allodynia and preserve established allodynia.

[0007] As mentioned above, the α 2 The δ subunit forms the binding site for gabapentin and pregabalin, structural derivatives of the inhibitory neurotransmitters GABA, but they do not bind to GABAA, GABAB, or benzodiazepine receptors or alter GABA regulation in animal brain preparations. v α 2 Binding of gabapentin and pregabalin to the δ subunit results in a reduction in calcium-dependent release of multiple neurotransmitters, providing efficacy and tolerability for neuropathic pain management. Gabapentinoids can also reduce excitability by inhibiting synaptogenesis (Perret and Luo, 2009, supra; Vink and Alewood, 2012, supra; Zamponi et al., 2015, supra).

[0008] The sigma-1 (σ1) receptor was discovered 40 years ago and was initially assigned to a novel subtype of the opioid family. This receptor is expressed both in the endoplasmic reticulum and in the plasma membrane and plays an important role in regulating intracellular calcium concentration. The signaling pathways associated with the activation of the σ1 receptor have not yet been described, but it is believed to function as an amplifier of the activation of intracellular cascades. In that sense, the σ1 receptor regulates and modulates the activity of many voltage-gated ion channels, including Ca2+-, K+-, Na+, Cl-, SK, and NMDA channels, as well as IP3 receptors.

[0009] It is also known that σ1 receptors are involved in analgesia, as σ1 receptor agonists counteract opioid receptor-mediated analgesia, while σ1 receptor antagonists such as haloperidol enhance it (Chien CC, Pasternak GW. Neurosci. Lett. 1995, 190, 137-9).

[0010] A large body of further preclinical evidence indicates a clear role for σ1 receptors in pain therapy (Zamanillo D, Romero L, Merlos M, Vela JM. Eur. J. Pharmacol., 2013, 716, 78-93). The generation of σ1 receptor knockout mice, which do not show any obvious phenotype and perceive sensory stimuli normally, was an important milestone in this endeavor. Under physiological conditions, the responses of σ1 receptor knockout mice to mechanical and thermal stimuli were found to be indistinguishable from those of WT, but they were shown to be much more resistant to the expression of pain behaviors than WT mice once hypersensitivity came into play. Thus, in σ1 receptor knockout mice, capsaicin did not induce mechanical hypersensitivity, both phases of formalin-induced pain were reduced, and cold and mechanical hypersensitivity were greatly reduced after partial sciatic nerve ligation or treatment with paclitaxel, which are models of neuropathic pain. Many of these effects have been confirmed by the use of σ1 receptor antagonists, leading one compound, S1RA, to advance to clinical trials for the treatment of various pain conditions. Compound S1RA significantly reduces neuropathic pain and anhedonia state after nerve injury (i.e., neuropathic pain state), and as demonstrated in operant self-administration model, nerve-injured mice obtain spontaneous responses to obtain this (presumably to obtain pain relief), but sham-operated mice do not, indicating that σ1 receptor antagonism reduces neuropathic pain and also addresses some of the comorbidities associated with pain conditions (i.e., anhedonia, a core symptom of depression) (Romero et al. Br J Pharmacol. 2012, 166, 2289-306).

[0011] Polypharmacology is the phenomenon whereby drugs bind to multiple targets rather than a single target with significant affinity. The effect of polypharmacology on therapy can be positive (effective therapy) and / or negative (side effects). Positive and / or negative effects can occur by binding to subsets of the same or different targets, and binding to some targets may have no effect. Multicomponent or multitarget drugs can overcome the toxicity and other side effects associated with high doses of a single drug by countering biological compensation, reducing the dosage of each compound, or accessing context-specific multitarget mechanisms. Because multitarget mechanisms require that their targets are available for coordinated action, synergistic effects are expected to occur in a narrower range of cellular phenotypes than the activity of a single agent, given differential expression of drug targets. Indeed, it has been experimentally demonstrated that synergistic drug combinations are generally more specific for a particular cellular context than single agent activity, and such selectivity is achieved by differential expression of the drug's targets in cell types that are relevant for therapeutic rather than toxic effects (Lehar et al., Nat. Biotechnol. 2009, 27, 659-666).

[0012] In the case of chronic pain, which is a multifactorial disease, multitarget drugs may provide a concerted pharmacological intervention of multiple targets and signaling pathways that promote pain. Because they exploit the biological complexity of the disease, multitarget (or multicomponent drug) approaches are among the most promising avenues for the treatment of multifactorial diseases such as pain (Gilron et al., Lancet Neurol. 2013, 12, 1084-95). In fact, positive synergistic interactions have been described for several compounds, including analgesics (Schroeder et al., J. Pharmacol. Exp Ther. 2011, 337, 312-20. Erratum in: J. Pharmacol. Exp. Ther. 2012, 342, 232; Zhang et al., Cell Death Dis. 2014, 5: e1138; Gilron et al., 2013 (supra)).

[0013] Given significant differences in pharmacokinetics, metabolism, and bioavailability, reformulation of drug combinations (multicomponent drugs) is difficult. Furthermore, two drugs that are generally safe when administered individually cannot be considered safe in combination. In addition to the possibility of adverse drug-drug interactions, if the theory of network pharmacology indicates that an effect on a phenotype can result from hitting multiple targets, the combined phenotypic perturbation can be either effective or harmful. A major challenge for both drug combination strategies is the regulatory requirement to demonstrate that each individual drug is safe, both as an individual agent and in combination (Hopkins et al, Nat. Chem. Biol. 2008, 4, 682-90).

[0014] An alternative strategy for multi-targeted therapy is to design single compounds with selective polypharmacology (multi-targeted drugs). Many approved drugs have been shown to act on multiple targets. Single compound dosing may have advantages over drug combinations in terms of equitable pharmacokinetics and biodistribution. Indeed, the trough of drug exposure due to incompatible pharmacokinetics between the components of a combination therapy may provide an opportunity for low dosing, where reduced selective pressure may lead to drug resistance. In terms of drug registration, approval of single compounds acting on multiple targets faces significantly lower regulatory barriers than approval of novel drug combinations (Hopkins, 2008 (supra)).

[0015] As mentioned above, the σ1 receptor and the α2δ1 subunit modulate intracellular calcium concentration and the activity of voltage-gated calcium channels. There is also robust clinical and preclinical evidence linking both targets to the treatment of chronic neuropathic pain. Thus, the present application aims to combine the α2δ1 subunit of the voltage-gated calcium channel in the same molecule to treat chronic pain. 2 The advantages of having dual activity towards the δ-1 subunit and σ1 receptors are also concerned.

[0016] Pain is diverse in nature, since in almost all pain conditions several mediators, signaling pathways and molecular mechanisms are involved. As a result, monomodal therapy can be complemented with dual mechanisms of action to provide complete pain relief. Nowadays, combining existing therapies is a common clinical practice, and great efforts are being made to evaluate the best combinations of available drugs in clinical research (Mao J, Gold MS, Backonja MJ Pain, 2011, 12, 157-166).

[0017] Thus, there remains a need to find compounds with alternative or improved pharmacological activity in the treatment of pain that are effective and exhibit the desired selectivity, and that also have good "druggability" properties, i.e., good pharmaceutical properties related to administration, distribution, metabolism, and excretion.

[0018] The authors of the present invention have discovered a novel method for the treatment of pain by inhibiting the α-terminal end of the voltage-gated calcium channel, which provides an innovative, effective, complementary and alternative solution to pain treatment. 2 δ subunits, especially α 2 A series of compounds that exhibit primary pharmacological activity against the delta-1 subunit, or the alpha subunit, of voltage-gated calcium channels. 2 δ subunits, especially α 2 Compounds have been discovered that exhibit dual pharmacological activity against both the δ-1 subunit and the σ1 receptor.

[0019] Considering the existing results of currently available therapies and clinical practice, the present invention provides a solution by combining a single compound that binds to two different targets relevant for pain treatment, mainly the σ1 receptor and the α1 receptor of the voltage-gated calcium channel. 2 δ subunits, especially α 2 This has been achieved by providing compounds of the present invention which bind to both the δ-1 subunits. Summary of the Invention [Means for solving the problem]

[0020] In this invention, the voltage-dependent calcium channel α 2 δ subunits, especially α 2 A family of structurally distinct homopiperazinyl and homopiperidinyl quinazolin-4(3H)-one derivatives encompassed by formula (I) which have pharmacological activity at both the δ-1 subunit and σ1 receptors has now been identified, thus solving the above-mentioned problem of identifying alternative or improved pain treatments by providing such compounds.

[0021] The main object of the present invention is to provide a method for the treatment of pain, comprising administering to a subject ... 2 δ subunits, especially α 2 The present invention relates to compounds that have dual activity by binding to the δ-1 subunit and the σ1 receptor.

[0022] The present invention is directed in a main aspect to compounds of general formula (I) [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', R y '''', W, w 1 , w 2 , w 3 , and w 4 is as defined in the detailed description below.

[0023] A further object of the present invention relates to a process for preparing the compounds of general formula (I).

[0024] A still further object of the present invention relates to the use of intermediate compounds for preparing compounds of general formula (I).

[0025] Pharmaceutical compositions containing the compounds of formula (I) are also an object of the present invention.

[0026] Finally, it is an object of the present invention to use the compounds as medicines, more specifically for treating pain and pain-related conditions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] The present invention relates to a voltage-dependent calcium channel α 2 δ subunits, especially α 2 The present invention relates to a family of structurally diverse homopiperazinyl and homopiperidinyl quinazolin-4(3H)-one derivatives that have dual pharmacological activity towards both the δ-1 subunit and σ1 receptors.

[0028] The present invention relates to a method for treating pain and related disorders comprising administering to the patient an α-terminal agonist of a voltage-gated calcium channel. 2 δ subunits, especially α 2 δ-1 subunit and σ 1 The present invention relates to compounds that have dual activity in binding to receptors.

[0029] The present invention relates to a voltage-dependent calcium channel α 2 δ subunits, especially α 2 δ-1 subunit and σ 1 The aim is to provide compounds, or a series of chemically related compounds, that act as dual ligands for the receptor, and therefore to provide compounds that respond to the following scales: K i Preferred are embodiments having bonds represented as: K i (σ 1) is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM. K i (α 2 δ-1) is preferably <10000 nM, more preferably <5000 nM, even more preferably <500 nM, or even more preferably <100 nM.

[0030] Preferably, K i (σ 1 ) >1000 nM, the following scale was adopted to represent binding to σ1 receptors: + K i (σ 1 )>1000nM, or a range of inhibition between 1% and 50%.

[0031] Preferably, K i (α 2 δ-1)>5000nM, α of voltage-dependent calcium channels 2 The following scale was adopted to describe binding to the δ-1 subunit: + K i (α 2 δ-1)>5000nM, 1%-50% inhibition range

[0032] The Applicant has surprisingly found that the problem of providing a new, effective and alternative solution for treating pain and pain-related disorders can be solved by an analgesic approach that combines two activities in a single drug (i.e., bifunctional and inhibits the sigma 1 receptor and the α1 voltage-gated calcium channel). 2 δ subunits, specifically α 2 They discovered that this could be resolved by using a dual ligand that binds to the δ-1 subunit.

[0033] As mentioned above, the σ1 receptor and the α2δ1 subunit modulate intracellular calcium concentration and the activity of voltage-gated calcium channels. There is also robust clinical and preclinical evidence linking both targets to the treatment of chronic neuropathic pain. Thus, the present invention provides a method for the treatment of pain by combining the α2δ1 subunit of the voltage-gated calcium channel in the same molecule. 2 It also relates to the advantages of having dual activity towards the δ-1 subunit and σ1 receptors (ie binding to two different targets relevant to the treatment of pain).

[0034] σ 1 Receptor and voltage-dependent calcium channel α 2 Dual compounds with binding to both δ subunits show great therapeutic potential by achieving excellent analgesia.

[0035] An additional advantage of using multiple designed ligands is that there is a lower risk of drug-drug interactions compared to cocktails or multi-component drugs, which leads to simpler pharmacokinetics and lower inter-patient variability. Furthermore, this approach can improve patient compliance and broaden therapeutic applications compared to monomechanistic drugs by addressing more complex pathogenesis.

[0036] However, it should be noted that the functions of "antagonism" and "agonism" are also subdivided into subfunctions such as partial agonism or inverse agonism with respect to their effects. Thus, the functionality of a compound should be considered within a relatively broad band.

[0037] Antagonists block or suppress agonist-mediated responses. Known secondary functions are neutral antagonists or inverse agonists.

[0038] An agonist increases the activity of a receptor above its base level. Known subfunctions are full agonism or partial agonism.

[0039] In its broader aspect, the present invention relates to compounds of general formula (I) [ka] During the ceremony, R y and R y ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Or, R y and R y ' together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; R y '' is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R y ''' and R y "'' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Or, R y ''' and R y " " together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; W is nitrogen or -CR w -, wherein R w is hydrogen or halogen, Or, R w and R 5 , R 5 ', R 5 '', or R 5 One of the '' forms a double bond, w1, w2, w3, and w4 are independently selected from the group consisting of nitrogen and carbon; R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 8 , -NR 8 R 8 ', -NR 8 C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R21 '', -SR 21 , -S(O)R 21 , -S(O) 2 R 21 , -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 is selected from In the formula, R 21 , R 21 ', and R 21 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R 3 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R 31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -CN, haloalkyl, haloalkoxy, -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR31 'R 31 '', and -C(CH 3 ) 3 OR 31 is selected from In the formula, R 31 , R 31 ', and R 31 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 3~6 Alkenyl, and substituted or unsubstituted C 3~6 alkynyl, R 4 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl; R 4 and R y together with the nitrogen and carbon atom to which they are attached, respectively, can form a substituted or unsubstituted heterocyclyl of 5 or 6 atoms; R 4 and R y "" together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 6-member substituted or unsubstituted heterocyclyl; R 5 , R 5 ', R 5 '', and R 5 ''' are independently hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Or, R 5 and R 5 ' and / or R 5 '' and R 5 ''' form a carbonyl group together with the carbon atom to which they are attached, R 6 , R 6 ', R 6 '', and R6 ''' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R 7 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 5 and R 5 ' is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 5 '' and R 5 One of the '''s is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 5 and R 5 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or R 5 and R 5 ' is R 6 '' and R 6 -[CH 2 ] n - forming crosslinks, or R 6 and R 6 ' is R 6 '' and R 6 -[CH 2 ] n - forming crosslinks, or R 6 and R6 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 6 '' and R 6 -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or wherein n is 1, 2, or 3; R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 It is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl.

[0040] These compounds according to the invention are optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0041] In another embodiment, these compounds according to the invention are optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof.

[0042] Please note that "or its corresponding salt" also means "or its corresponding pharma-ceutically acceptable salt". This also applies to all embodiments described below, and thus the use of "salt" is equivalent to "pharma-ceutically acceptable salt".

[0043] In certain embodiments, the following conditions apply: w1, w2, w3, and w4 are all carbon, or one or two of w1, w2, w3, and w4 are nitrogen while the others are carbon.

[0044] In a further embodiment, the compound according to the invention is a compound of general formula (I) [ka] During the ceremony, R y and R y ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Or, R y and R y ' together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; R y '' is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R y ''' and R y"'' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Or, R y ''' and R y " " together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; W is nitrogen or -CR w -, wherein R w is hydrogen or halogen, Or, R w and R 5 , R 5 ', R 5 '', or R 5 One of the '' forms a double bond, w1, w2, w3, and w4 are independently selected from the group consisting of nitrogen and carbon; w1, w2, w3, and w4 are all carbon or one or two of w1, w2, w3, and w4 are nitrogen while the others are carbon; R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 8 , -NR 8 R 8 ', -NR 8 C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; During the ceremony, R 1 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 11 , halogen, -CN, haloalkoxy, and -NR 11 R 11 ', and R 1 Cycloalkyl, arylheterocyclyl, as defined above in alkylcycloalkyl, alkylaryl, and alkylheterocyclyl, when substituted, are ═O, halogen, —R 11 , -OR 11 , -NO 2 , -NR 11 R 11 ', -NR 11 C(O)R 11 ', -NR 11 S(O) 2 R 11 ', -S(O) 2 NR 11 R 11 ', -NR 11 C(O)NR 11 'R 11 '', -SR 11 , -S(O)R 11 , -S(O) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(O)OR 11 , -C(O)NR 11 R 11 ',-OCH 2 CH 2 OR 11 , -NR 11 S(O) 2 NR 11 'R 11 '', -C(CH 3 ) 2 OR 11 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 11 , R 11 ', and R 11'' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; During the ceremony, R 8 or R 8 When substituted, alkyl, alkenyl, or alkynyl as defined in the above formula (I) may be selected from the group consisting of -OR 81 , halogen, -CN, haloalkoxy, and -NR 81 R 81 ', and R 8 or R 8 Cycloalkyl, heterocyclyl, or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 81 , -OR 81 , -NO 2 , -NR 81 R 81 ', -NR 81 C(O)R 81 ', -NR 81 S(O) 2 R 81 ', -S(O) 2 NR 81 R 81 ', -NR 81 C(O)NR81 'R 81 '', -SR 81 , -S(O)R 81 , -S(O) 2 R 81 , -CN, haloalkyl, haloalkoxy, -C(O)OR 81 , -C(O)NR 81 R 81 ',-OCH 2 CH 2 OR 81 , -NR 81 S(O) 2 NR 81 'R 81 '', and -C(CH 3 ) 2 OR 81 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; In the formula, R 81 , R 81 ', and R 81 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R 21 '', -SR21 , -S(O)R 21 , -S(O) 2 R 21 , -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 is selected from In the formula, R 21 , R 21 ', and R 21 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R 3 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R 31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -CN, haloalkyl, haloalkoxy, -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR 31 'R31 '', and -C(CH 3 ) 3 OR 31 is selected from In the formula, R 31 , R 31 ', and R 31 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 3~6 Alkenyl, and substituted or unsubstituted C 3~6 alkynyl, R 4 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl; During the ceremony, R 4 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 41 , halogen, -CN, -C(O)OR 41 , haloalkoxy, -NR 41 R 41 ', substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aryl; R 4 Cycloalkyl, as also defined in alkylcycloalkyl, or heterocyclyl in alkylheterocyclyl, or aryl in alkylaryl, may be substituted, and if the substitution is not otherwise defined, this may include halogen, -R 41 , -OR 41 , -NO 2 , -NR 41 R 41 ', -NR 41 C(O)R 41 ', -NR 41 S(O) 2 R 41 ', -S(O) 2 NR 41 R 41', -NR 41 C(O)NR 41 'R 41 '', -SR 41 , -S(O)R 41 , -S(O) 2 R 41 , -CN, haloalkyl, haloalkoxy, -C(O)OR 41 , -C(O)NR 41 R 41 ',-OCH 2 CH 2 OR 41 , -NR 41 S(O) 2 NR 41 'R 41 '', and -C(CH 3 ) 2 OR 41 and is substituted with one or more substituents selected from In the formula, R 41 , R 41 ', and R 41 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R 4 and R y together with the nitrogen and carbon atom to which they are attached, respectively, can form a substituted or unsubstituted heterocyclyl of 5 or 6 atoms; R 4 and R y "" together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 6-member substituted or unsubstituted heterocyclyl; R 5 , R 5 ', R 5 '', and R 5 ''' are independently hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C2~6 alkynyl, Or, R 5 and R 5 ' and / or R 5 '' and R 5 ''' form a carbonyl group together with the carbon atom to which they are attached, During the ceremony, R 5 , R 5 ', R 5 '', and R 5 When the alkyl, alkenyl, or alkynyl in ''' is substituted, it may be -OR 51 , -C(O)OR 51 , halogen, -CN, haloalkoxy, and -NR 51 R 51 ', and In the formula, R 51 and R 51 ' is independently selected from hydrogen, unsubstituted C1-5 alkyl, unsubstituted C2-5 alkenyl, and unsubstituted C2-5 alkynyl; R 6 , R 6 ', R 6 '', and R 6 ''' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, During the ceremony, R 6 , R 6 ', R 6 '', and R 6 When the alkyl, alkenyl, or alkynyl in ''' is substituted, it may be -OR 61 , -C(O)OR 61 , halogen, -CN, haloalkoxy, and -NR 61 R 61 ', and In the formula, R 61 and R 61 ' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl and unsubstituted C2~6 alkynyl, R 7 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; During the ceremony, R 7 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 71 , halogen, -CN, haloalkoxy, and -NR 71 R 71 ', and R 7 Cycloalkylheterocyclyl or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 71 , -OR 71 , -NO 2 , -NR 71 R 71 ', -NR 71 C(O)R 71 ', -NR 71 S(O) 2 R 71 ', -S(O) 2 NR 71 R 71 ', -NR 71 C(O)NR 71 'R 71 '', -SR 71 , -S(O)R 71 , -S(O) 2 R 71 , -CN, haloalkyl, haloalkoxy, -C(O)OR 71 , -C(O)NR 71 R 71 ',-OCH 2 CH 2 OR 71 , -NR 71S(O) 2 NR 71 'R 71 '', and -C(CH 3 ) 2 OR 71 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; In the formula, R 71 , R 71 ', and R 71 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, R 5 and R 5 ' is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 5 '' and R 5 One of the '''s is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 5 and R 5 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or R 5 and R 5 ' is R 6 '' and R 6 -[CH 2 ] n - forming crosslinks, or R 6 and R 6 ' is R 6 '' and R 6 -[CH 2 ]n - forming crosslinks, or R 6 and R 6 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 7 Together with -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 6 '' and R 6 -[CH 2 ] n - forming crosslinks, or R 9 and R 9 ' is R 5 '' and R 5 -[CH 2 ] n - forming crosslinks, or wherein n is 1, 2, or 3; R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; During the ceremony, R 9 or R 9 When substituted, alkyl, alkenyl, or alkynyl as defined in the above formula (I) may be selected from the group consisting of -OR 91 , halogen, -CN, haloalkoxy, and -NR 91 R 91', and R 9 or R 9 Cycloalkyl, heterocyclyl, or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 91 , -OR 91 , -NO 2 , -NR 91 R 91 ', -NR 91 C(O)R 91 ', -NR 91 S(O) 2 R 91 ', -S(O) 2 NR 91 R 91 ', -NR 91 C(O)NR 91 'R 91 '', -SR 91 , -S(O)R 91 , -S(O) 2 R 91 , -CN, haloalkyl, haloalkoxy, -C(O)OR 91 , -C(O)NR 91 R 91 ',-OCH 2 CH 2 OR 91 , -NR 91 S(O) 2 NR 91 'R 91 '', and -C(CH 3 ) 2 OR 91 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; In the formula, R 91 , R 91 ', and R 91 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6alkynyl, Alkyl, alkenyl, or alkynyl are substituted, and unless the substitution is otherwise defined, are represented by -OR 13 , halogen, -CN, haloalkoxy, and -NR 13 R 13 ', and In the formula, R 13 and R 13 ' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl and unsubstituted C 2~6 alkynyl, Any aryl, heterocyclyl, or cycloalkyl in alkylaryl, alkylheterocyclyl, or alkylcycloalkyl may be substituted, and unless the substitution is otherwise defined, may include halogen, -R 14 , -OR 14 , -NO 2 , -NR 14 R 14 ', -NR 14 C(O)R 14 ', -NR 14 S(O) 2 R 14 ', -S(O) 2 NR 14 R 14 ', -NR 14 C(O)NR 14 'R 14 '', -SR 14 , -S(O)R 14 , -S(O) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(O)OR 14 , -C(O)NR 14 R 14 ',-OCH 2 CH 2 OR 14 , -NR 14 S(O) 2 NR 14 'R 14 '', and -C(CH 3 ) 2 OR 14 and is substituted with one or more substituents selected from In the formula, R 14 , R 14 ', and R 14 '' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl, unsubstituted C 2~6 selected from alkynyl, unsubstituted aryl, unsubstituted cycloalkyl, and unsubstituted heterocyclyl; Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0045] In a further embodiment, the compound according to the invention of the general formula (I) ’ ) [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', W, w 1 , w 2 , w 3 , and w 4 is as defined in the detailed description below, Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0046] In a further embodiment, the compound according to the invention of the general formula (I) 2 ') [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', W, w 1 , w 2 , w 3 , and w 4 is as defined in the detailed description below, Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0047] In a further embodiment, the compound according to the invention of the general formula (I) 3 ') [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , W, w 1 , w 2 , w 3 , and w 4 is as defined in the detailed description below, Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0048] In a further embodiment, the compound according to the invention of the general formula (I) 4 ') [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 6 '', R 7 , W, w 1 , w 2 , w 3 , and w 4 is as defined in the detailed description below, Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0049] In a further embodiment, the compound according to the invention of the general formula (I) 5 ') [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 7 , R 9 , W, w 1 , w 2 , w 3 , and w 4is as defined in the detailed description below, Optionally in the form of one of the stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of the stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0050] For clarity, all groups and definitions described herein and referring to compounds of general formula (I) are defined as compounds of general Markush formula (I') (I 2 '), (I 3 '), (I 4 '), or (I 5 This also applies to the general Markush formula (I') (I ') (where applicable), and to all synthetic intermediates (if these groups are present in the general Markush formula mentioned), 2 '), (I 3 '), (I 4 '), or (I 5 ') falls within the broader definition of the general Markush formula (I).

[0051] For clarity, e.g., "R 8 -R 8 'Ring in' is R 8 and R 8 ' means the ring resulting when R 1 ' and R 2 ' form a ring together with the atom to which they are attached. This ring may or may not subsequently be substituted. This definition is also generally applicable and may also be used in conjunction with, for example, "R i -R i’ The ring in R i and R i It can also be applied as a definition of any other ring (preferably cycloalkyls, heterocyclyls, or aryls) formed from two different functional groups, such as "a" means the ring obtained when they form a ring together with the atom to which they are attached, which ring may or may not be subsequently substituted.

[0052] In the context of the present invention, alkyl is understood to mean a saturated, straight or branched chain hydrocarbon which may be unsubstituted or substituted once or several times. This includes, for example, -CH 3 and -CH 2 -CH 3 Among these radicals, C 1~2 Alkyl represents C1 or C2 alkyl, C 1~3 Alkyl represents C1, C2, or C3 alkyl; 1~4 Alkyl represents C1, C2, C3, or C4 alkyl; 1~5 Alkyl represents C1, C2, C3, C4, or C5 alkyl; 1~6 Alkyl represents C1, C2, C3, C4, C5, or C6 alkyl; 1~7 Alkyl represents C1, C2, C3, C4, C5, C6, or C7 alkyl; 1~8 Alkyl represents C1, C2, C3, C4, C5, C6, C7, or C8 alkyl; 1~10 Alkyl represents C1, C2, C3, C4, C5, C6, C7, C8, C9, or C10 alkyl; 1~18 Alkyl represents C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17 or C18 alkyl. The alkyl radical is preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, and, if substituted, further CHF. 2 , C.F. 3 , or C.H. 2 Preferably, alkyl in the context of the present invention is C1-8 alkyl, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl, preferably C 1~6 Alkyl is understood as, for example, methyl, ethyl, propyl, butyl, pentyl or hexyl, more preferably C1-4 alkyl, for example methyl, ethyl, propyl or butyl.

[0053] Alkenyl is understood to mean an unsaturated straight or branched chain hydrocarbon which may be unsubstituted or substituted once or several times. This includes, for example, -CH=CH-CH 3 The alkenyl radical is preferably vinyl (ethenyl), allyl (2-propenyl). Preferably, in the context of the present invention, alkenyl is C2-10 alkenyl or C2-8 alkenyl, such as ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene, or C 2~6 Alkenyl, for example, ethylene, propylene, butylene, pentylene, or hexylene; or C2-4 alkenyl, for example, ethylene, propylene, or butylene.

[0054] Alkynyl is understood to mean an unsaturated straight or branched chain hydrocarbon which may be unsubstituted or substituted once or several times. This includes, for example, -C=C-CH 3 Preferably, alkynyl in the context of the present invention is C2-10 alkynyl or C2-8 alkynyl, such as ethyne, propyne, butyne, pentyne, hexyne, heptyne or octyne, or C 2~6 Alkynyl, such as ethyne, propyne, butyne, pentyne, or hexyne; or C2-4 alkynyl, such as ethyne, propyne, butyne, pentyne, or hexyne.

[0055] In connection with alkyl (and alkylaryl, alkylheterocyclyl, or alkylcycloalkyl), alkenyl, alkynyl, and O-alkyl, unless otherwise defined, the term substituted in the context of the present invention means that at least one hydrogen radical has been replaced with a halogen (F, Cl, Br, I), -NR k R k’ , -SR k , -S(O)R k , -S(O) 2 R k , -OR k , -C(O)R k, -C(O)OR k , -CN, -C(O)NR k R k’ , haloalkyl, haloalkoxy, R k is R 11 , R 13 , R 41 , R 51 , R 61 , R 71 , R 81 , or R 91 It is represented by (R k’ is R 11 ', R 13 ', R 41 ', R 51 ', R 61 ', R 71 ', R 81 ' or R 91 '), where R 1 ~R 91 '' is as defined herein, where the radical R 1 ~R 91 When both are present in formula I, they may be the same or different.

[0056] Most preferably, in relation to alkyl (and alkylaryl, alkylheterocyclyl, or alkylcycloalkyl), alkenyl, alkynyl, or O-alkyl, substituted means, in the context of the present invention, halogen (F, Cl, Br, I), -NR k R k’ , -OR k , -CN, -SR k , haloalkyl, haloalkoxy, any alkyl (and alkylaryl, alkylheterocyclyl, or alkylcycloalkyl), alkenyl, alkynyl, or O-alkyl substituted with one or more of the following: k is R 11 , R 13 , R 41 , R 51 , R 61 , R 71 , R 81 , or R 91 It is represented by (R k’ is R11 ', R 13 ', R 41 ', R 51 ', R 61 ', R 71 ', R 81 ' or R 91 '), where R 1 ~R 91 '' is as defined herein, where the radical R 1 ~R 91 When both are present in formula I, they may be the same or different.

[0057] Two or more substitutions with the same or different substituents are possible on the same molecule and on the same carbon atom. This is the case, for example, when three hydrogens are substituted with CF 3 on the same C atom, as in the case of, for example, -CH(OH)-CH=CH-CHCl 2 This includes substitutions at different positions on the same molecule, such as in the case of

[0058] In the context of the present invention, haloalkyl is understood to mean that alkyl is substituted one or several times with halogen (selected from F, Cl, Br, I). This means, for example, -CH 2 Cl, -CH 2 F, -CHCl 2 , -CHF 2 , -CCl 3 , -CF 3 , and -CH 2 -CHCI 2 Preferably, haloalkyl is understood in the context of the present invention as meaning halogen-substituted C1-4 alkyl, which represents halogen-substituted C1, C2, C3 or C4 alkyl. Thus, halogen-substituted alkyl radicals are preferably methyl, ethyl, propyl and butyl. Preferred examples include -CH 2 Cl, -CH 2 F, -CHCl 2 , -CHF 2 , and -CF 3 Examples include:

[0059] In the context of the present invention, haloalkoxy is understood to mean that -O-alkyl is substituted one or several times with halogen (selected from F, Cl, Br, I). This means, for example, -OCH 2 Cl, -OCH 2 F, -OCHCl 2 , -OCHF 2 , -OCCl 3 , -OCF 3 , and -OCH 2 -CHCI 2 Preferably, haloalkoxy is understood in the context of the present invention as meaning that halogen-substituted -OC1-4 alkyl represents halogen-substituted C1, C2, C3 or C4 alkoxy. Thus, halogen-substituted alkyl radicals are preferably O-methyl, O-ethyl, O-propyl and O-butyl. Preferred examples include -OCH 2 Cl, -OCH 2 F, -OCHCl 2 , -OCHF 2 , and -OCF 3 Examples include:

[0060] In the context of the present invention, cycloalkyl is understood to mean saturated and unsaturated (but not aromatic) cyclic hydrocarbons (containing no heteroatoms in the ring), which may be unsubstituted or substituted once or several times. Further, C3-4 cycloalkyl represents C3 or C4 cycloalkyl, C3-5 cycloalkyl represents C3, C4 or C5 cycloalkyl, C3-6 cycloalkyl represents C3, C4, C5 or C6 cycloalkyl, C3-7 cycloalkyl represents C3, C4, C5, C6 or C7 cycloalkyl, C3-8 cycloalkyl represents C3, C4, C5, C6, C7 or C8 cycloalkyl, C4-5 cycloalkyl represents C4 or C5 cycloalkyl, C4-6 cycloalkyl represents C4, C5 or C6-cycloalkyl, C4-7 cycloalkyl represents C4, C5, C6 or C7 cycloalkyl, C5-6 cycloalkyl represents C5 or C6 cycloalkyl and C5-7 cycloalkyl represents C5, C6 or C7 cycloalkyl. Examples are cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, and also adamantyl. Preferably, in the context of the present invention, cycloalkyl is a C3-8 cycloalkyl thereof, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, or a C3-7 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, or a C3-6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, in particular cyclopentyl or cyclohexyl.

[0061] Aryl is understood to mean a 5-18 membered monocyclic or polycyclic ring system containing at least one aromatic ring but not containing any heteroatoms in the ring. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl or indanyl, 9H-fluorenyl or anthracenyl radicals, which may be unsubstituted or substituted once or several times. Most preferably, aryl is understood in the context of the present invention to be phenyl, naphthyl or anthracenyl, preferably phenyl.

[0062] A heterocyclyl radical or group (hereinafter also referred to as heterocyclyl) is understood as meaning a 5-18 membered mono- or polycyclic heterocyclic ring system containing at least one saturated or unsaturated ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur in the ring. The heterocyclic group may also be substituted once or several times.

[0063] Subgroups within heterocyclyl as understood herein include heteroaryl and non-aromatic heterocyclyl. Heteroaryl (corresponding to heteroaromatic radical or aromatic heterocyclyl) is an aromatic 5-18 membered mono- or polycyclic heterocyclic ring system of one or more rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur, preferably a 5-18 membered mono- or polycyclic aromatic heterocyclic ring system of one or two rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur, more preferably selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, oxazole, thiophene and benzimidazole, - non-aromatic heterocyclyl is a 5-18 membered mono- or polycyclic heterocyclic ring system of one or more rings, at least one of which (wherein this (or these) rings) contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and / or sulfur, preferably a 5-18 membered mono- or polycyclic heterocyclic ring system of one or two rings, at least one of which (wherein this (or these) rings) contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and / or sulfur, more preferably selected from oxazepane, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, in particular benzodioxane, morpholine, tetrahydropyran, piperidine, oxopyrrolidine and pyrrolidine.

[0064] Preferably, in the context of the present invention, heterocyclyl is defined as a 5-18 membered mono- or polyheterocyclic ring system with one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur.Preferably, this is a 5-18 membered mono- or polyheterocyclic ring system with one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur.

[0065] Preferred examples of heterocyclyl include oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, tetrahydroisoquinoline, phthalazine, benzo-1,2, These include 5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole, and quinazoline, in particular pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyran, pyrazole, imidazole, piperidine, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, pyrimidine, oxazepanazetidine, and pyrrolidine.

[0066] In the context of the present invention, oxopyrrolidine is understood as meaning pyrrolidin-2-one.

[0067] N-containing heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring nitrogen and optionally one or more further heteroatoms selected from the group consisting of nitrogen, oxygen and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, The aryl group is selected from tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzimidazole, indazole, benzothiazole, benzodiazole, morpholine, indoline, triazole, isoxazole, pyrazole, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, carbazole, or thiazole.

[0068] In the context of the present invention, a cyclic amide is defined as at least one sequence which forms part of a ring. [ka] (as defined above). The cyclic amides may be optionally fused with a ring system. Preferably, the cyclic amides are "indolin-2-ones". The cyclic amides may be substituted or unsubstituted as defined above for heterocyclyl.

[0069] In the context of the present invention, a cyclic urea is defined as a ring having at least one sequence forming part of the ring. [ka] (as defined above). The cyclic urea may be optionally fused with a ring system. Preferably, the cyclic urea is "1H-benzo[d]imidazol-2(3H)-one". The cyclic urea may be substituted or unsubstituted as defined above for heterocyclyl.

[0070] In relation to aromatic heterocyclyl (heteroaryl), non-aromatic heterocyclyl, aryl and cycloalkyl, when a ring system simultaneously meets two or more of the above definitions, if at least one aromatic ring contains a heteroatom, the ring system is first defined as aromatic heterocyclyl (heteroaryl). If the aromatic ring does not contain a heteroatom, if at least one non-aromatic ring contains a heteroatom, the ring system is defined as non-aromatic heterocyclyl. If the non-aromatic ring does not contain a heteroatom, if the ring system contains at least one aryl ring, it is defined as aryl. If no aryl is present, if at least one non-aromatic cyclic hydrocarbon is present, the ring system is defined as cycloalkyl.

[0071] In the context of the present invention, alkylaryl is any of the C aryls which may be branched or linear and which are unsubstituted or substituted once or several times. 1~6 It is understood as meaning an aryl group (see above) connected to another atom via an alkyl (see above). Preferably, alkylaryl is a group having one to four (-CH 2 is understood to mean an aryl group (see above) connected to another atom via a -) group. Most preferably, alkylaryl is benzyl (i.e., -CH 2 -phenyl). More preferably, the "alkyl" in alkylaryl is an unsubstituted alkyl.

[0072] In the context of the present invention, alkylheterocyclyl is intended to mean any heterocyclic or heterocyclic group which may be branched or straight-chain and which is unsubstituted or substituted once or several times. 1~6It is understood as meaning a heterocyclyl group connected to another atom via an alkyl (see above). Preferably, an alkylheterocyclyl is a heterocyclyl group having one to four (-CH 2 is understood to mean a heterocyclyl group (see above) connected to another atom via a -) group. More preferably, alkylheterocyclyl is -CH 2 -pyridine. More preferably, the "alkyl" in alkylheterocyclyl is an unsubstituted alkyl.

[0073] In the context of the present invention, alkylcycloalkyl is intended to mean any alkyl group which may be branched or linear and which is unsubstituted or substituted once or several times. 1~6 It is understood as meaning a cycloalkyl group connected to another atom via an alkyl (see above). Preferably, alkylcycloalkyl is a cycloalkyl group having 1 to 4 (-CH 2 is understood to mean a cycloalkyl group (see above) connected to another atom via a -) group. Most preferably, alkylcycloalkyl is -CH 2 -cyclopropyl. More preferably, the "alkyl" in alkylcycloalkyl is an unsubstituted alkyl.

[0074] Preferably, the aryl is a monocyclic aryl. More preferably, the aryl is a 5, 6, or 7 membered monocyclic aryl. Even more preferably, the aryl is a 5 or 6 membered monocyclic aryl.

[0075] Preferably, the heteroaryl is a monocyclic heteroaryl. More preferably, the heteroaryl is a 5-, 6-, or 7-membered monocyclic heteroaryl. Even more preferably, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl.

[0076] Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably, the non-aromatic heterocyclyl is a 4-, 5-, 6-, or 7-membered monocyclic non-aromatic heterocyclyl. Even more preferably, the non-aromatic heterocyclyl is a 5- or 6-membered monocyclic non-aromatic heterocyclyl.

[0077] Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferably, the cycloalkyl is a 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic cycloalkyl. Even more preferably, the cycloalkyl is a 3-, 4-, 5-, or 6-membered monocyclic cycloalkyl.

[0078] Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzimidazole, benzofuran ... The benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, oxaspirodecan, or thiazole.

[0079] Generally, such heterocyclyls may contain 3 to 32 atoms in the ring (preferably 4 to 20 atoms in the ring, or most preferably 5 to 18 atoms in the ring). Thus, in the case of a heterocyclyl of one saturated or unsaturated ring, the heterocyclyl may contain 3 to 12 atoms in the ring (preferably 4 to 10 atoms in the ring, or 5 to 8 atoms in the ring, or 5 to 6 atoms in the ring). Such heterocyclyls may also, in the case of a heterocyclyl of two saturated or unsaturated rings, contain 5 to 22 atoms in total for both rings, preferably 6 to 16 atoms in total for both rings, or 7 to 12 atoms in total for both rings, or 8 to 10 atoms in total for both rings). Such heterocyclyls may also contain, in the case of heterocyclyls of three saturated or unsaturated rings, 7 to 32 atoms in total for the three rings (preferably 10 to 22 atoms in total for the three rings, or 12 to 20 atoms in total for the three rings, or 10 to 18 atoms in total for the three rings).

[0080] In relation to aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted means, unless otherwise defined, halogen (F, Cl, Br, I), -R k , -OR k , -CN, -NO 2 , -NR k R k’ , -C(O)OR k , -NR k C(O)R k’ , -C(O)NR k R k’ , -NR k S(O) 2 R k’ , =O, -OCH 2 CH 2 OH, -NR k C(O)NR k’ R k’’ , -S(O) 2 NR k R k’ , -NR k S(O) 2 NR k’ Rk’’ , haloalkyl, haloalkoxy, -SR k , -S(O)R k , -S(O) 2 R k , or -C(CH 3 ) OR k or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, R k , R k’ , and R k’’ are independently H or saturated or unsaturated, linear or branched, substituted or unsubstituted C 1~6 Alkyl, saturated or unsaturated, straight or branched, substituted or unsubstituted C 1~6 Alkyl, saturated or unsaturated, straight or branched chain, substituted or unsubstituted -OC 1~6 Alkyl (alkoxy), saturated or unsaturated, straight or branched chain, substituted or unsubstituted -SC 1~6 Alkyl, saturated or unsaturated, straight or branched chain, substituted or unsubstituted -C(O)-C 1~6 Alkyl groups, saturated or unsaturated, straight or branched chain, substituted or unsubstituted -C(O)-OC 1~6 alkyl group, substituted or unsubstituted aryl or alkyl-aryl, substituted or unsubstituted cycloalkyl or alkyl-alkyl, substituted or unsubstituted heterocyclyl or alkyl-heterocyclyl, R k is R 11 , R 14 , R 41 , R 71 , R 81 , or R 91 is one of (R k ' is R 11 ', R 14 ', R 41 ', R 71 ', R 81 ' or R 91' and R k '' is R 11 '', R 14 '', R 41 '', R 71 '', R 81 '', or R 91 ''), where R 1 ~R 91 '' is as defined herein, where the radical R 1 ~R 91 When both are present in formula I, they may be the same or different.

[0081] Most preferably, in relation to aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkyl-heterocyclyl), substituted means in the context of the present invention that any aryl, cycloalkyl, and heterocyclyl that is substituted is selected from the group consisting of halogen (F, Cl, Br, I), -R k , -OR k , -CN, -NO 2 , -NR k R k’’’ , N.R. k C(O)R k’ , -NR k S(O) 2 R k’ , -S(O) 2 NR k R k’ , -NR k C(O)NR k’ R k’’ , haloalkyl, haloalkoxy, -SR k , -S(O)R k , or -S(O) 2 R k or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl (as well as alkylaryl, alkylcycloalkyl, or alkylheterocyclyl); k is R 11 , R 14 , R 41 , R71 , R 81 , or R 91 is one of (R k ' is R 11 ', R 14 ', R 41 ', R 71 ', R 81 ' or R 91 ' and R k '' is R 11 '', R 14 '', R 41 '', R 71 '', R 81 '', or R 91 ''), where R 1 ~R 91 '' is as defined herein, where the radical R 1 ~R 91 When both are present in formula I, they may be the same or different.

[0082] In relation to cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl), i.e. non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted means, unless otherwise defined, [ka] (resulting in a spiro structure), and / or by ═O, is understood to mean the substitution of a cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl ring system.

[0083] Furthermore, in relation to cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl), i.e. non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted is understood to mean that the substitution of the cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl ring system is spiro substituted or substituted with =O, unless otherwise defined.

[0084] Furthermore, in relation to cycloalkyl (including alkyl-cycloalkyl), or heterocyclyl (including alkylheterocyclyl), i.e. non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), substituted is understood to mean, unless otherwise defined, the replacement of the cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl ring system by =O.

[0085] A ring system is an organic system consisting of at least one ring of connected atoms, but also includes systems in which two or more rings of connected atoms are joined (polycyclic ring systems), where "jointed" means that each ring shares one (as in a spiro structure), two or more atoms that are member(s) of both joined rings.

[0086] The term "polycyclic ring" means a ring system made up of two or more rings joined by sharing at least one atom.

[0087] The term "leaving group" refers to a molecular fragment that leaves with a pair of electrons in a heterolytic bond cleavage. Leaving groups can be anionic or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters such as tosylate (TsO-) or mesylate.

[0088] The term "salt" should be understood to mean any form of the active compound used according to the invention, which is in ionic form or charged, combined with counterions (cations or anions) or in solution form. This also includes complexes of the active compound with other molecules and ions, in particular complexes resulting from ionic interactions.

[0089] The term "physiologically acceptable salt" in the context of the present invention means any salt which is physiologically acceptable (meaning in most cases not toxic, in particular not resulting in toxicity due to counter ions) when used appropriately in therapy, in particular when used or applied to humans and / or mammals.

[0090] These physiologically acceptable salts may be formed with cations or bases and are understood in the context of the present invention, in particular when used in humans and / or mammals, to mean salts of at least one of the compounds used according to the invention as an anion (usually a (deprotonated) acid) and at least one physiologically acceptable, preferably inorganic, cation. Salts of alkali metals and alkaline earth metals, and also NH 4 Of these, the (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium, or calcium salts are particularly preferred.

[0091] Physiologically acceptable salts may also be formed with anions or acids, and in the context of the present invention, particularly when used in humans and / or mammals, are understood to mean salts of at least one of the compounds used according to the present invention as cations and at least one physiologically acceptable anion.By this, in particular in the context of the present invention, salts formed with physiologically acceptable acids are understood, i.e., in particular when used in humans and / or mammals, salts of certain active compounds with physiologically acceptable inorganic or organic acids.Examples of physiologically acceptable salts of certain acids are the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.

[0092] The compounds of the invention may exist in crystalline form or in the form of a free compound such as a free base or acid.

[0093] Any compound that is a solvate of the compound according to the present invention, such as the compound according to general formula I defined above, is also understood to be included in the scope of the present invention. Methods of solvation are generally known in the art. Suitable solvates are pharma-ceutically acceptable solvates. The term "solvate" according to the present invention should be understood to mean any form of the active compound according to the present invention, in which another molecule (possibly a polar solvent) is bound via a non-covalent bond. Particularly preferred examples include hydrates and alcoholates, such as methanolates or ethanolates.

[0094] Any compound that is a prodrug of a compound according to the present invention, such as a compound according to general formula I defined above, is also understood to be included in the scope of the present invention. The term "prodrug" is used in its broadest sense and includes derivatives that are converted to the compounds of the present invention in vivo. Such derivatives can be easily imagined by those skilled in the art and include, depending on the functional groups present in the molecule, the following derivatives of the compounds of the present invention, but are not limited to: esters, amino acid esters, phosphate esters, metal salts, sulfonates, carbamates, and amides. Examples of well-known methods for generating prodrugs of a given active compound are known to those skilled in the art and can be found, for example, in Krogsgaard-Larsen et al. "Textbook of Drug design and Discovery" Taylor & Francis (April 2002).

[0095] It is understood that any compound that is an N-oxide of a compound according to the invention, such as a compound according to general formula I defined above, is also included within the scope of the present invention.

[0096] Unless otherwise specified, the compounds of the invention are also intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, the replacement of hydrogen by deuterium or tritium, or 13 C or 14 Replacement of carbon with C-rich carbon, or 15 Compounds having the present structures except for the replacement of a nitrogen with an N-rich nitrogen are within the scope of this invention, and this is particularly true of the provisos above, such that any reference to hydrogen or any "H" in the formula also includes deuterium or tritium.

[0097] The compound of formula (I) and its salts or solvates of this compound are preferably in pharma-ceutically acceptable or substantially pure form. Pharmaceutically acceptable form means, inter alia, having a pharma-ceutically acceptable level of purity, excluding normal pharmaceutical excipients such as diluents and carriers, and not containing materials that are considered toxic at normal dosage levels. The purity level of the drug substance is preferably greater than 50%, more preferably greater than 70%, and most preferably greater than 90%. In a preferred embodiment, this is greater than 95% of the compound of formula (I) or its salt. This also applies to its solvates or prodrugs.

[0098] In a further embodiment, the compounds according to the invention of general formula (I) are R y and R y ' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0099] In a further embodiment, the compounds according to the invention of general formula (I) are R y and R y ' are both hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0100] In a further embodiment, the compounds according to the invention of general formula (I) are R y '' is hydrogen and substituted or unsubstituted C 1~6alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0101] In a further embodiment, the compounds according to the invention of general formula (I) are R y '' is hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0102] In a further embodiment, the compounds according to the invention of general formula (I) are R y ''' and R y '''' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0103] In a further embodiment, the compounds according to the invention of general formula (I) are R y ''' and R y '''' are both hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0104] In a further embodiment, the compounds according to the invention of general formula (I) are R w is hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0105] In a further embodiment, the compounds according to the invention of general formula (I) are R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 8 , -NR 8 R 8 ', -NR 8 C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0106] In a further embodiment, the compounds according to the invention of general formula (I) are R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 8 , -NR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted aryl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0107] In a further embodiment, the compounds according to the invention of general formula (I) are R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R 21 '', -SR 21 , -S(O)R 21 , -S(O) 2 R 21, -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 is selected from Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0108] In a further embodiment, the compounds according to the invention of general formula (I) are R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl and -OR 21 is selected from Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0109] In a further embodiment, the compounds according to the invention of general formula (I) are R 3 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR 31 'R 31 '', and -C(CH 3 ) 3 OR 31 is selected from Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0110] In a further embodiment, the compounds according to the invention of general formula (I) are R 3 is hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0111] In a further embodiment, the compounds according to the invention of general formula (I) are R 4 is substituted or unsubstituted C 1~6 selected from alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0112] In a further embodiment, the compounds according to the invention of general formula (I) are R 4 is hydrogen, substituted or unsubstituted C 1~6 selected from alkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylcycloalkyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0113] In a further embodiment, the compounds according to the invention of general formula (I) are R 4 and R y together with the nitrogen and carbon atom to which they are attached, can form a 6-member substituted or unsubstituted heterocyclyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0114] In a further embodiment, the compounds according to the invention of general formula (I) are R 4 and R y "" together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 6-member substituted or unsubstituted heterocyclyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0115] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 , R 5 ', R 5 '', and R 5 ''' independently represents hydrogen, halogen, and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0116] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 , R 5 ', R 5 '', and R 5 ''' are all hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0117] In a further embodiment, the compounds according to the invention of general formula (I) are R 6 , R 6 ', R 6 '', and R 6 ''' is independently hydrogen and substituted or unsubstituted C 1~6alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0118] In a further embodiment, the compounds according to the invention of general formula (I) are R 7 is hydrogen, substituted or unsubstituted C 1~6 selected from the group consisting of alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0119] In a further embodiment, the compounds according to the invention of general formula (I) are R 7 is hydrogen, substituted or unsubstituted C 1~6 selected from the group consisting of alkyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0120] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 and R 5' is R 7 Together with -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0121] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 '' and R 5 One of the '''s is R 7 Together with -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0122] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 and R 5 ' is R 5 '' and R 5 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0123] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 and R 5 ' is R 6 '' and R 6 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0124] In a further embodiment, the compounds according to the invention of general formula (I) are R 6 and R 6 ' is R 6 '' and R 6 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0125] In a further embodiment, the compounds according to the invention of general formula (I) are R 6 and R 6 ' is R 5 '' and R 5 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0126] In a further embodiment, the compounds according to the invention of general formula (I) are R 9 and R 9 ' is R 6 '' and R 6 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0127] In a further embodiment, the compounds according to the invention of general formula (I) are R 9 and R 9 ' is R 5 '' and R 5 -[CH 2 ] n - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0128] In a further embodiment, the compounds according to the invention of general formula (I) are n is 2, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0129] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 and R 5 ' is R 7 With -CH 2 CH 2 - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0130] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 '' and R 5 One of the '''s is R 7 With -CH 2 CH 2 - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0131] In a further embodiment, the compounds according to the invention of general formula (I) are R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6selected from the group consisting of alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0132] In a further embodiment, the compounds according to the invention of general formula (I) are R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 selected from the group consisting of alkyl, and substituted or unsubstituted heterocyclyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0133] In a further embodiment, the compounds according to the invention of general formula (I) are R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 selected from the group consisting of alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0134] In a further embodiment, the compounds according to the invention of general formula (I) are R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , and substituted or unsubstituted C 1~6 is selected from the group consisting of alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0135] In a further embodiment, the compounds according to the invention of general formula (I) are R 11 , R 11 ', and R 11 '' is independently hydrogen, substituted or unsubstituted C 1~6 selected from alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0136] In a further embodiment, the compounds according to the invention of general formula (I) are R 11 , R 11 ', and R 11 '' is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0137] In a further embodiment, the compounds according to the invention of general formula (I) are R 13 and R 13 ' are independently hydrogen and unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0138] In a further embodiment, the compounds according to the invention of general formula (I) are R 14 , R 14 ', and R 14 '' are independently hydrogen, unsubstituted C 1~6 selected from alkyl, unsubstituted aryl, unsubstituted cycloalkyl, and unsubstituted heterocyclyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0139] In a further embodiment, the compounds according to the invention of general formula (I) are R 21 , R 21 ', and R 21 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0140] In a further embodiment, the compounds according to the invention of general formula (I) are R 21 is substituted or unsubstituted C 1~6 is alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0141] In a further embodiment, the compounds according to the invention of general formula (I) are R 31 , R 31 ', and R 31 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0142] In a further embodiment, the compounds according to the invention of general formula (I) are R 41 , R 41 ', and R 41'' is independently hydrogen, substituted or unsubstituted C 1~6 selected from alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0143] In a further embodiment, the compounds according to the invention of general formula (I) are R 41 , R 41 ', and R 41 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0144] In a further embodiment, the compounds according to the invention of general formula (I) are R 51 and R 51 ' is independently selected from hydrogen and unsubstituted C1-5 alkyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0145] In a further embodiment, the compounds according to the invention of general formula (I) are R 61 and R 61 ' are independently hydrogen and unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0146] In a further embodiment, the compounds according to the invention of general formula (I) are R 71 , R 71 ', and R 71 '' is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0147] In a further embodiment, the compounds according to the invention of general formula (I) are R 81 , R 81 ', and R 81 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0148] In a further embodiment, the compounds according to the invention of general formula (I) are R 81 is substituted or unsubstituted C 1~6 is alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0149] In a further embodiment, the compounds according to the invention of general formula (I) are R 91 , R 91 ', and R 91 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0150] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R y and R y ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or Or, R y and R y ' together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; and / or R y '' is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R y ''' and R y " " is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or Or, R y ''' and R y " " together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; and / or W is nitrogen or -CR w - and and / or R w is hydrogen or halogen, and / or R w and R 5 , R 5 ', R 5 '', or R 5 One of the '' forms a double bond, and / or w1 is selected from the group consisting of nitrogen and carbon; and / or w2 is selected from the group consisting of nitrogen and carbon; and / or w3 is selected from the group consisting of nitrogen and carbon; and / or w4 is selected from the group consisting of nitrogen and carbon; and / or R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 8 , -NR 8 R 8 ', -NR 8C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R 21 '', -SR 21 , -S(O)R 21 , -S(O) 2 R 21 , -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 is selected from and / or R 3 is hydrogen, halogen, substituted or unsubstituted C1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R 31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -CN, haloalkyl, haloalkoxy, -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR 31 'R 31 '', and -C(CH 3 ) 3 OR 31 is selected from and / or R 4 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl; and / or R 4 and R y together with the nitrogen and carbon atom to which they are attached, respectively, can form a substituted or unsubstituted heterocyclyl of 5 or 6 atoms; and / or R 4 and R y"" together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 6-member substituted or unsubstituted heterocyclyl; and / or R 5 , R 5 ', R 5 '', and R 5 ''' are independently hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R 5 and R 5 ' and / or R 5 '' and R 5 ''' form a carbonyl group together with the carbon atom to which they are attached, and / or R 6 , R 6 ', R 6 '', and R 6 ''' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R 7 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 5 and R 5 ' is R 7 Together with -[CH 2 ] n - Forms bridges, and / or n is 1, 2, or 3; and / or R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 11 , R 11 ', and R 11 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 13 and R 13 ' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl and unsubstituted C 2~6 alkynyl, and / or R 14 , R 14 ', and R 14 '' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl, unsubstituted C 2~6 selected from alkynyl, unsubstituted aryl, unsubstituted cycloalkyl, and unsubstituted heterocyclyl; and / or R 21 , R 21 ', and R 21 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R 31 , R 31 ', and R 31 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 3~6 Alkenyl, and substituted or unsubstituted C 3~6 alkynyl, and / or R 41 , R 41 ', and R 41 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; and / or R 51 and R 51 ' is independently selected from hydrogen, unsubstituted C1-5 alkyl, unsubstituted C2-5 alkenyl, and unsubstituted C2-5 alkynyl; and / or R 61and R 61 ' are independently hydrogen, unsubstituted C 1~6 Alkyl, unsubstituted C 2~6 Alkenyl and unsubstituted C 2~6 alkynyl, and / or R 71 , R 71 ', and R 71 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R 81 , R 81 ', and R 81 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, and / or R 91 , R 91 ', and R 91 '' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0151] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R y and R y 'In C 1~6alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0152] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R y In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0153] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R y ''' and R y In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, etc. 3~7 Cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.3~6 is cycloalkyl, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0154] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 1 In The alkyl in the alkylaryl, alkylheterocyclyl, alkylcycloalkyl, haloalkyl, or haloalkoxy is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 alkyl, more preferably alkyl is methyl; and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 alkyl is methyl or ethyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl, more preferably aryl is phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0155] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 2 In The alkyl in the haloalkyl or haloalkoxy is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, etc. 1~6 is alkyl, and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0156] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 3 In The alkyl in the haloalkyl or haloalkoxy is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, etc. 1~6 is alkyl, and / or C 1~6alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0157] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 4 In The alkyl in the alkylaryl, alkylheterocyclyl, alkylcycloalkyl, haloalkyl, or haloalkoxy is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 alkyl, more preferably alkyl is methyl; and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 alkyl is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or isopentyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, more preferably cycloalkyl is cyclopropyl; and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thi ... selected from azole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazoleoctahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline, preferably heterocyclyl is furan; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0158] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 5 , R 5 ', R 5 '', and R 5 In ''', C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0159] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 6 , R 6 ', R 6 '', and R 6 In ''', C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0160] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 7 In The alkyl in the alkylaryl, alkylheterocyclyl, or alkylcycloalkyl is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 alkyl, more preferably alkyl is methyl; and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 alkyl is methyl or ethyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl, more preferably aryl is phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0161] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 8 and R 8'In The alkyl in the alkylaryl, alkylheterocyclyl, or alkylcycloalkyl is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 is alkyl, and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazolyl, benzodiazole ... azole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazoleoctahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline, preferably heterocyclyl is piperidine; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0162] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 9 and R 9 'In The alkyl in the alkylaryl, alkylheterocyclyl, alkylcycloalkyl, haloalkyl, or haloalkoxy is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl.1~6 is alkyl, and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0163] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 11 , R 11 ', and R 11 In The alkyl in the alkylaryl, alkylheterocyclyl, or alkylcycloalkyl is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 is alkyl, and / or C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0164] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 13 and R 13 'In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0165] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 14 , R 14 ', and R 14 In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8 cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0166] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 21 , R 21 ', and R 21 In C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0167] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 31 , R 31 ', and R 31 In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0168] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 41 , R 41 ', and R 41 In The alkyl in the alkylaryl, alkylheterocyclyl, or alkylcycloalkyl is C 1, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl. 1~6 is alkyl, and / or C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; and / or Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, etc. 3~8cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. 3~7 cycloalkyl, more preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3~6 is cycloalkyl, and / or aryl is selected from phenyl, naphthyl, or anthracene, preferably naphthyl and phenyl; and / or Heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, preferably a heterocyclic ring system of one or two saturated or unsaturated rings, at least one of which contains in the ring one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and / or sulfur, more preferably oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, selected from benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspirondecane, indolin-2-one, and quinazoline; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0169] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 51 and R 51 'In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0170] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 61 and R 61 'In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0171] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 71 , R 71 ', and R 71 In C 1~6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0172] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 81 , R 81 ', and R 81 In C 1~6Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0173] In another preferred embodiment of the invention according to general formula (I), the compound is one in which R 91 , R 91 ', and R 91 In C 1~6 Alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably C 1~6 The alkyl is methyl; and / or C 2~6 alkyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene, and isobutylene; and / or C 2~6 Alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne, and isobutyne; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0174] In another preferred embodiment of the invention according to general formula (I), the compound has the formula W is nitrogen or -CR w -, wherein R w is hydrogen or halogen, and preferably W is nitrogen or -CR w -, wherein R w is hydrogen, more preferably W is nitrogen or -CH-; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0175] In another preferred embodiment of the invention according to general formula (I), the compound has the formula w 1 is nitrogen or carbon, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0176] In another preferred embodiment of the invention according to general formula (I), the compound has the formula w 2 is nitrogen or carbon, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0177] In another preferred embodiment of the invention according to general formula (I), the compound has the formula w 3 is nitrogen or carbon, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0178] In another preferred embodiment of the invention according to general formula (I), the compound has the formula w 4 is nitrogen or carbon, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0179] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R y and R y ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y and R y ' are both hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0180] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R y '' is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y '' is hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0181] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R y ''' and R y " " is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y and R y ' are both hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0182] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 8 , -NR 8 R 8 ', -NR 8 C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 is selected from the group consisting of: -, ... 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 8 , -NR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted aryl, and substituted or unsubstituted alkylaryl, more preferably R 1 is hydrogen, bromine, chlorine, fluorine, iodine, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, -NH (methylpiperidine), -CN, -OCH 3 , -OH, -CF 3 , -OCF 3 , substituted or unsubstituted phenyl, substituted or unsubstituted benzyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0183] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R 21 '', -SR 21 , -S(O)R 21 , -S(O) 2 R 21 , -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 Preferably, R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl and -OR 21 More preferably, R 2 is hydrogen, fluorine, bromine, chlorine, substituted or unsubstituted methyl, and -OCH 3 is selected from Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0184] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 3 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R 31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -CN, haloalkyl, haloalkoxy, -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR 31 'R 31 '', and -C(CH 3 ) 3 OR 31 Preferably, R 3 is hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0185] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 4 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl, preferably R 4 is hydrogen, substituted or unsubstituted C 1~6 is selected from alkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylcycloalkyl, more preferably R 4 is hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted isobutyl, substituted or unsubstituted isopentyl, -CH 2 COOH, -CH 2 CH 2 OCH 3 , substituted or unsubstituted -CH 2 -cyclopropyl, and substituted or unsubstituted -CH 2 - Selected from Franc, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0186] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R4 and R y together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 5- or 6-membered substituted or unsubstituted heterocyclyl, preferably R 4 and R y can form, together with the nitrogen and carbon atoms to which they are attached, a 6-membered substituted or unsubstituted heterocyclyl, more preferably R 4 and R y together with the nitrogen and carbon atoms to which they are attached can form a substituted or unsubstituted piperidine, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0187] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 5 , R 5 ', R 5 '', and R 5 ''' are independently hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 5 , R 5 ', R 5 '', and R 5 ''' are all hydrogen, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0188] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 6 , R6 ', R 6 '', and R 6 ''' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 6 , R 6 ', R 6 '', and R 6 ''' is independently hydrogen and substituted or unsubstituted C 1~6 alkyl, more preferably R 6 , R 6 ', R 6 '', and R 6 "'' is independently selected from hydrogen and substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0189] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 7 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 7 is hydrogen, substituted or unsubstituted C 1~6 More preferably, R is selected from the group consisting of alkyl, and substituted or unsubstituted alkylaryl. 7 is selected from the group consisting of hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted benzyl, and substituted or unsubstituted phenethyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0190] In a further embodiment, the compounds according to the invention of general formula (I) are R 5 and R 5 ', but R 7 Together with -[CH 2 ] n - forms a bridge, preferably R 5 and R 5 ', but R 7 With -CH 2 CH 2 - Forms bridges, Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0191] In a further embodiment, the compounds according to the invention of general formula (I) are R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 is selected from the group consisting of alkyl, and substituted or unsubstituted heterocyclyl, more preferably R8 and R 8 ' is independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, and substituted or unsubstituted piperidine; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0192] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , and substituted or unsubstituted C 1~6 alkyl, more preferably R 9 and R 9 ' are independently hydrogen, fluorine, -CH 2 OCH 3 , —OH, substituted or unsubstituted methyl, and substituted or unsubstituted ethyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0193] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 21 , R 21 ', and R 21 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 21 is substituted or unsubstituted C 1~6 is preferably alkyl, more preferably R 21 is substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0194] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 41 , R 41 ', and R 41 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, preferably R 41 is selected from hydrogen and substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0195] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 81 is substituted or unsubstituted C 1~6 alkyl, preferably R 81 is substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0196] In another preferred embodiment of the invention according to general formula (I), the compound has the formula R 91 , R 91 ', and R 91 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, preferably R 91 is selected from hydrogen and substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0197] In another preferred embodiment of the invention according to general formula (I), the compound has the formula W is nitrogen or -CR w -, wherein R w is hydrogen or halogen, and / or w 1 is nitrogen or carbon, and / or w 2 is nitrogen or carbon, and / or w 3 is nitrogen or carbon, and / or w 4 is nitrogen or carbon, and / or R y and R y ' is independently hydrogen, substituted or unsubstituted C 1~6Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y and R y ' are both hydrogen, and / or R y '' is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y '' is hydrogen, and / or R y ''' and R y " " is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R y and R y ' are both hydrogen, and / or R 1 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 8 , -NR 8 R 8 ', -NR 8 C(O)R 8 ', -NR 8 C(O)OR 8 ', -C(O)NR 8 R 8 ', -C(O)OR 8 , -OCHR 8 R 8 is selected from the group consisting of: -, ... 1is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, -OR 8 , -NR 8 R 8 ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted aryl, and substituted or unsubstituted alkylaryl, more preferably R 1 is hydrogen, bromine, chlorine, fluorine, iodine, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, -NH (methylpiperidine), -CN, -OCH 3 , -OH, -CF 3 , -OCF 3 , substituted or unsubstituted phenyl, substituted or unsubstituted benzyl; and / or R 2 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 21 , -NO 2 , -NR 21 R 21 ', -NR 21 C(O)R 21 ', -NR 21 S(O) 2 R 21 ', -S(O) 2 NR 21 R 21 ', -NR 21 C(O)NR 21 'R 21 '', -SR 21 , -S(O)R 21 , -S(O) 2 R 21 , -CN, haloalkyl, haloalkoxy, -C(O)OR 21 , -C(O)NR 21 R 21 ', -NR 21 S(O) 2 NR 21 'R 21 '', and -C(CH 3 ) 2 OR 21 Preferably, R 2is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl and -OR 21 More preferably, R 2 is hydrogen, fluorine, bromine, chlorine, substituted or unsubstituted methyl, and -OCH 3 is selected from and / or R 3 is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, -OR 31 , -NO 3 , -NR 31 R 31 ', -NR 31 C(O)R 31 ', -NR 31 S(O) 3 R 31 ', -S(O) 3 NR 31 R 31 ', -NR 31 C(O)NR 31 'R 31 '', -SR 31 , -S(O)R 31 , -S(O) 3 R 31 , -CN, haloalkyl, haloalkoxy, -C(O)OR 31 , -C(O)NR 31 R 31 ', -NR 31 S(O) 3 NR 31 'R 31 '', and -C(CH 3 ) 3 OR 31 Preferably, R 3 is hydrogen, and / or R 4 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl, preferably R 4 is hydrogen, substituted or unsubstituted C 1~6 is selected from alkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylcycloalkyl, more preferably R 4 is hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted isobutyl, substituted or unsubstituted isopentyl, -CH 2 COOH, -CH 2 CH 2 OCH 3 , substituted or unsubstituted -CH 2 -cyclopropyl, and substituted or unsubstituted -CH 2 - Selected from Franc, and / or R 4 and R y together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 5- or 6-membered substituted or unsubstituted heterocyclyl, preferably R 4 and R y can form, together with the nitrogen and carbon atoms to which they are attached, a 6-membered substituted or unsubstituted heterocyclyl, more preferably R 4 and R y together with the nitrogen and carbon atoms to which they are attached can form a substituted or unsubstituted piperidine, and / or R 5 , R 5 ', R 5 '', and R 5 ''' are independently hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 5 , R 5 ', R 5 '', and R 5 ''' are all hydrogen, and / or R 6 , R 6 ', R 6 '', and R 6 ''' are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 6 , R 6 ', R 6 '', and R 6 ''' is independently hydrogen and substituted or unsubstituted C 1~6 alkyl, more preferably R 6 , R 6 ', R 6 '', and R 6 "'' is independently selected from hydrogen and substituted or unsubstituted methyl; and / or R 7 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 7 is hydrogen, substituted or unsubstituted C 1~6 More preferably, R is selected from the group consisting of alkyl, and substituted or unsubstituted alkylaryl. 7 is selected from the group consisting of hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted benzyl, and substituted or unsubstituted phenethyl; and / or R 5 , R 5 ', R 5 '', and R 5 One of the '''s is R 7 With -CH 2 CH 2 - forms a bridge, preferably R 5 and R 5' is R 7 With -CH 2 CH 2 - forming bridges, and / or R 5 '' and R 5 One of the '''s is R 7 With -CH 2 CH 2 -bridges, more preferably R 5 and R 5 ' is R 7 With -CH 2 CH 2 - Forming bridges or and / or R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 8 and R 8 ' is independently hydrogen, substituted or unsubstituted C 1~6 is selected from the group consisting of alkyl, and substituted or unsubstituted heterocyclyl, more preferably R 8 and R 8 ' is independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, and substituted or unsubstituted piperidine; and / or R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6is selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl, preferably R 9 and R 9 ' are independently hydrogen, halogen, -OR 91 , and substituted or unsubstituted C 1~6 alkyl, more preferably R 9 and R 9 ' are independently hydrogen, fluorine, -CH 2 OCH 3 , —OH, substituted or unsubstituted methyl, and substituted or unsubstituted ethyl; and / or R 21 , R 21 ', and R 21 '' is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, and substituted or unsubstituted C 2~6 alkynyl, preferably R 21 is substituted or unsubstituted C 1~6 is preferably alkyl, more preferably R 21 is substituted or unsubstituted methyl; and / or R 41 , R 41 ', and R 41 '' are independently hydrogen and substituted or unsubstituted C 1~6 alkyl, preferably R 41 is selected from hydrogen and substituted or unsubstituted methyl; and / or R 81 is substituted or unsubstituted C 1~6 alkyl, preferably R 81 is substituted or unsubstituted methyl; and / or R 91 , R 91 ', and R 91 '' are independently hydrogen and substituted or unsubstituted C 1~6alkyl, preferably R 91 is selected from hydrogen and substituted or unsubstituted methyl; Optionally, the compound is in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0198] In a preferred embodiment, W is nitrogen or -CR w -It is.

[0199] In a preferred embodiment, R w is hydrogen.

[0200] In a preferred embodiment, w 1 is nitrogen or carbon.

[0201] In a preferred embodiment, w 2 is nitrogen or carbon.

[0202] In a preferred embodiment, w 3 is nitrogen or carbon.

[0203] In a preferred embodiment, w 4 is nitrogen or carbon.

[0204] In a preferred embodiment, w 1 , w 2 , w 3 , and w 4 is all carbon.

[0205] In a preferred embodiment, w 1 is nitrogen, while w 2 , w 3 , and w 4 is all carbon.

[0206] In a preferred embodiment, w 2 is nitrogen, while w 1 , w3 , and w 4 is all carbon.

[0207] In a preferred embodiment, w 3 is nitrogen, while w 2 , w 1 , and w 4 is all carbon.

[0208] In a preferred embodiment, w 4 is nitrogen, while w 2 , w 3 , and w 1 is all carbon.

[0209] In a preferred embodiment, R y and R y ' are both hydrogen.

[0210] In a preferred embodiment, R y '' is hydrogen.

[0211] In a preferred embodiment, R y and R y ' are both hydrogen.

[0212] In a preferred embodiment, R 1 is hydrogen, bromine, chlorine, fluorine, iodine, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, -NH (methylpiperidine), -CN, -OCH 3 , -OH, -CF 3 , -OCF 3 , substituted or unsubstituted phenyl, and substituted or unsubstituted benzyl.

[0213] In a preferred embodiment, R 2 is hydrogen, fluorine, bromine, chlorine, substituted or unsubstituted methyl, and -OCH 3 is selected from.

[0214] In a preferred embodiment, R 3 is hydrogen.

[0215] In a preferred embodiment, R 4 is hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted isobutyl, substituted or unsubstituted isopentyl, -CH 2 COOH, -CH 2 CH 2 OCH 3 , substituted or unsubstituted -CH 2 -cyclopropyl, and substituted or unsubstituted -CH 2 -Fran is selected.

[0216] In a preferred embodiment, R 4 and R y can form a substituted or unsubstituted piperidine together with the nitrogen and carbon atoms to which they are attached.

[0217] In a preferred embodiment, R 5 , R 5 ', R 5 '', and R 5 ''' are all hydrogen.

[0218] In a preferred embodiment, R 6 , R 6 ', R 6 '', and R 6 "'' is independently selected from hydrogen and substituted or unsubstituted methyl.

[0219] In a preferred embodiment, R 6 is selected from hydrogen and substituted or unsubstituted methyl.

[0220] In a preferred embodiment, R 6 is selected from hydrogen.

[0221] In a preferred embodiment, R 6 '' is selected from hydrogen and substituted or unsubstituted methyl.

[0222] In a preferred embodiment, R 6 ``'' is selected from hydrogen and substituted or unsubstituted methyl.

[0223] In a preferred embodiment, R 6 is selected from hydrogen and substituted or unsubstituted methyl, while R 6 ' is hydrogen.

[0224] In a preferred embodiment, R 6 is substituted or unsubstituted methyl, while R 6 ' is hydrogen.

[0225] In a preferred embodiment, R 6 and R 6 ' are both hydrogen.

[0226] In a preferred embodiment, R 6 '' is selected from hydrogen and substituted or unsubstituted methyl, while R 6 ``'' is selected from hydrogen and substituted or unsubstituted methyl.

[0227] In a preferred embodiment, R 6 '' is selected from hydrogen, while R 6 ``'' is selected from hydrogen and substituted or unsubstituted methyl.

[0228] In a preferred embodiment, R 6 '' is a substituted or unsubstituted methyl, while R 6 ``'' is selected from hydrogen and substituted or unsubstituted methyl.

[0229] In a preferred embodiment, R 6 '' and R 6 Both ''' are hydrogen.

[0230] In a preferred embodiment, R 6 '' and R 6 Both "'' are substituted or unsubstituted methyl.

[0231] In a preferred embodiment, R 7 is selected from the group consisting of hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted benzyl, and substituted or unsubstituted phenethyl.

[0232] In a preferred embodiment, R 5 and R 5 ' is R 7 With -CH 2 CH 2 - Forming bridges.

[0233] In a preferred embodiment, R 8 and R 8 ' is independently selected from the group consisting of hydrogen, substituted or unsubstituted methyl, and substituted or unsubstituted piperidine.

[0234] In a preferred embodiment, R 8 is selected from the group consisting of hydrogen, and substituted or unsubstituted methyl.

[0235] In a preferred embodiment, R 8 ' is a substituted or unsubstituted piperidine.

[0236] In a preferred embodiment, R 8 is selected from the group consisting of hydrogen and substituted or unsubstituted methyl, while R 8 ' is a substituted or unsubstituted piperidine.

[0237] In a preferred embodiment, R 8 is hydrogen, while R 8 ' is a substituted or unsubstituted piperidine.

[0238] In a preferred embodiment, R 9 and R 9 ' are independently hydrogen, fluorine, -CH 2 OCH 3 , —OH, substituted or unsubstituted methyl, and substituted or unsubstituted ethyl.

[0239] In a preferred embodiment, R 9 are hydrogen, fluorine, -CH 2 OCH 3 , —OH, substituted or unsubstituted methyl, and substituted or unsubstituted ethyl, while R9 ' is selected from the group consisting of hydrogen, and substituted or unsubstituted methyl.

[0240] In a preferred embodiment, R 9 is substituted or unsubstituted methyl, while R 9 ' is selected from the group consisting of hydrogen, and substituted or unsubstituted methyl.

[0241] In a preferred embodiment, R 9 is substituted or unsubstituted methyl, while R 9 ' is hydrogen.

[0242] In a preferred embodiment, R 9 and R 9 Both ' are substituted or unsubstituted methyl.

[0243] In a preferred embodiment, R 9 is substituted or unsubstituted ethyl, while R 9 ' is hydrogen.

[0244] In a preferred embodiment, R 9 is -OH, while R 9 ' is hydrogen.

[0245] In a preferred embodiment, R 9 and R 9 ' are both hydrogen.

[0246] In a preferred embodiment, R 9 and R 9 ' are both fluorine.

[0247] In a preferred embodiment, R 21 is substituted or unsubstituted methyl.

[0248] In a preferred embodiment, R 41 is selected from hydrogen and substituted or unsubstituted methyl.

[0249] In a preferred embodiment, R 81is substituted or unsubstituted methyl.

[0250] In a preferred embodiment, R 91 is selected from hydrogen and substituted or unsubstituted methyl.

[0251] In a preferred embodiment, haloalkyl is -CF 3 It is.

[0252] In a preferred embodiment, the haloalkoxy is -OCF 3 It is.

[0253] In a preferred embodiment, R 1 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 11 , halogen, -CN, haloalkoxy, and -NR 11 R 11 ' is substituted with one or more substituents selected from

[0254] In a preferred embodiment, R 1 When substituted, alkyl, alkenyl, or alkynyl as defined herein are substituted with one or more halogens.

[0255] In a preferred embodiment, R 1 Alkyl as defined herein, when substituted, is substituted with one or more halogens.

[0256] In a preferred embodiment, R 1 Cycloalkyl, arylheterocyclyl, as defined above in alkylcycloalkyl, alkylaryl, and alkylheterocyclyl, when substituted, are ═O, halogen, —R 11 , -OR 11 , -NO 2 , -NR 11 R 11 ', -NR 11 C(O)R 11 ', -NR 11 S(O) 2 R 11 ', -S(O) 2 NR11 R 11 ', -NR 11 C(O)NR 11 'R 11 '', -SR 11 , -S(O)R 11 , -S(O) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(O)OR 11 , -C(O)NR 11 R 11 ',-OCH 2 CH 2 OR 11 , -NR 11 S(O) 2 NR 11 'R 11 '', -C(CH 3 ) 2 OR 11 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl.

[0257] In a preferred embodiment, R 8 or R 8 When substituted, alkyl, alkenyl, or alkynyl as defined in the above formula (I) may be selected from the group consisting of -OR 81 , halogen, -CN, haloalkoxy, and -NR 81 R 81 ' is substituted with one or more substituents selected from

[0258] In a preferred embodiment, R 8 or R 8 ' is an alkyl group as defined above, when substituted, such as -OR 81 , halogen, -CN, haloalkoxy, and -NR 81 R 81 ' is substituted with one or more substituents selected from

[0259] In a preferred embodiment, R 8 or R 8Cycloalkyl, heterocyclyl, or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 81 , -OR 81 , -NO 2 , -NR 81 R 81 ', -NR 81 C(O)R 81 ', -NR 81 S(O) 2 R 81 ', -S(O) 2 NR 81 R 81 ', -NR 81 C(O)NR 81 'R 81 '', -SR 81 , -S(O)R 81 , -S(O) 2 R 81 , -CN, haloalkyl, haloalkoxy, -C(O)OR 81 , -C(O)NR 81 R 81 ',-OCH 2 CH 2 OR 81 , -NR 81 S(O) 2 NR 81 'R 81 '', and -C(CH 3 ) 2 OR 81 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl.

[0260] In a preferred embodiment, R 8 or R 8 ' and also within alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, cycloalkyl, heterocyclyl, or aryl, when substituted, may include one or more -R 81 is replaced by.

[0261] In a preferred embodiment, R 4 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 41 , halogen, -CN, -C(O)OR 41 , haloalkoxy, -NR 41 R 41 ', substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aryl.

[0262] In a preferred embodiment, R 4 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 41 and -C(O)OR 41 is substituted with one or more substituents selected from:

[0263] In a preferred embodiment, R 4 When substituted, alkyl may be -OR 41 and -C(O)OR 41 is substituted with one or more substituents selected from:

[0264] In a preferred embodiment, R 4 Cycloalkyl, as also defined in alkylcycloalkyl, or heterocyclyl in alkylheterocyclyl, or aryl in alkylaryl, may be substituted, and if the substitution is not otherwise defined, it may be selected from halogen, -R 41 , -OR 41 , -NO 2 , -NR 41 R 41 ', -NR 41 C(O)R 41 ', -NR 41 S(O) 2 R 41 ', -S(O) 2 NR 41 R 41 ', -NR 41 C(O)NR 41 'R 41 '', -SR 41 , -S(O)R 41, -S(O) 2 R 41 , -CN, haloalkyl, haloalkoxy, -C(O)OR 41 , -C(O)NR 41 R 41 ',-OCH 2 CH 2 OR 41 , -NR 41 S(O) 2 NR 41 'R 41 '', and -C(CH 3 ) 2 OR 41 is substituted with one or more substituents selected from:

[0265] In a preferred embodiment, R 5 , R 5 ', R 5 '', and R 5 When the alkyl, alkenyl, or alkynyl in ''' is substituted, it may be -OR 51 , -C(O)OR 51、 Halogen, -CN, haloalkoxy, and -NR 51 R 51 ' is substituted with one or more substituents selected from

[0266] In a preferred embodiment, R 5 , R 5 ', R 5 '', and R 5 If the alkyl in ''' is substituted, it can be -OR 51 , -C(O)OR 51、 Halogen, -CN, haloalkoxy, and -NR 51 R 51 ' is substituted with one or more substituents selected from

[0267] In a preferred embodiment, R 6 , R 6 ', R 6 '', and R 6 When the alkyl, alkenyl, or alkynyl in ''' is substituted, it may be -OR 61 , -C(O)OR 61 , halogen, -CN, haloalkoxy, and -NR61 R 61 ' is substituted with one or more substituents selected from

[0268] In a preferred embodiment, R 6 , R 6 ', R 6 '', and R 6 If the alkyl in ''' is substituted, it can be -OR 61 , -C(O)OR 61 , halogen, -CN, haloalkoxy, and -NR 61 R 61 ' is substituted with one or more substituents selected from

[0269] In a preferred embodiment, R 7 When substituted, alkyl, alkenyl, or alkynyl as defined above may be selected from the group consisting of -OR 71 , halogen, -CN, haloalkoxy, and -NR 71 R 71 ' is substituted with one or more substituents selected from

[0270] In a preferred embodiment, R 7 When substituted, alkyl may be -OR 71 , halogen, -CN, haloalkoxy, and -NR 71 R 71 ' is substituted with one or more substituents selected from

[0271] In a preferred embodiment, R 7 Cycloalkylheterocyclyl or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 71 , -OR 71 , -NO 2 , -NR 71 R 71 ', -NR 71 C(O)R 71 ', -NR 71 S(O) 2 R 71 ', -S(O) 2 NR 71R 71 ', -NR 71 C(O)NR 71 'R 71 '', -SR 71 , -S(O)R 71 , -S(O) 2 R 71 , -CN, haloalkyl, haloalkoxy, -C(O)OR 71 , -C(O)NR 71 R 71 ',-OCH 2 CH 2 OR 71 , -NR 71 S(O) 2 NR 71 'R 71 '', and -C(CH 3 ) 2 OR 71 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl.

[0272] In a preferred embodiment, R 9 or R 9 When substituted, alkyl, alkenyl, or alkynyl as defined in the above formula (I) may be selected from the group consisting of -OR 91 , halogen, -CN, haloalkoxy, and -NR 91 R 91 ' is substituted with one or more substituents selected from

[0273] In a preferred embodiment, R 9 or R 9 ' is an alkyl group as defined above, when substituted, such as -OR 91 , halogen, -CN, haloalkoxy, and -NR 91 R 91 ' is substituted with one or more substituents selected from

[0274] In a preferred embodiment, R 9 or R 9When substituted, alkyl, alkenyl, or alkynyl as defined in the above may be one or more -OR 91 is replaced by.

[0275] In a preferred embodiment, R 9 or R 9 ' may be substituted with one or more -OR 91 is replaced by.

[0276] In a preferred embodiment, R 9 or R 9 Cycloalkyl, heterocyclyl, or aryl, as defined in and among alkylcycloalkyl, alkylheterocyclyl, and alkylaryl, when substituted, may include ═O, halogen, —R 91 , -OR 91 , -NO 2 , -NR 91 R 91 ', -NR 91 C(O)R 91 ', -NR 91 S(O) 2 R 91 ', -S(O) 2 NR 91 R 91 ', -NR 91 C(O)NR 91 'R 91 '', -SR 91 , -S(O)R 91 , -S(O) 2 R 91 , -CN, haloalkyl, haloalkoxy, -C(O)OR 91 , -C(O)NR 91 R 91 ',-OCH 2 CH 2 OR 91 , -NR 91 S(O) 2 NR 91 'R 91 '', and -C(CH 3 ) 2 OR 91, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl.

[0277] In preferred embodiments, the alkyl, alkenyl, or alkynyl is substituted, and unless the substitution is otherwise defined, is -OR 13 , halogen, -CN, haloalkoxy, and -NR 13 R 13 ' is substituted with one or more substituents selected from

[0278] In preferred embodiments, alkyl is substituted, and unless the substitution is otherwise defined, is -OR 13 , halogen, -CN, haloalkoxy, and -NR 13 R 13 ' is substituted with one or more substituents selected from

[0279] In preferred embodiments, the aryl, heterocyclyl, or cycloalkyl in alkylaryl, alkylheterocyclyl, or alkylcycloalkyl is substituted, and unless the substitution is otherwise defined, is selected from halogen, -R 14 , -OR 14 , -NO 2 , -NR 14 R 14 ', -NR 14 C(O)R 14 ', -NR 14 S(O) 2 R 14 ', -S(O) 2 NR 14 R 14 ', -NR 14 C(O)NR 14 'R 14 '', -SR 14 , -S(O)R 14 , -S(O) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(O)OR 14 , -C(O)NR14 R 14 ',-OCH 2 CH 2 OR 14 , -NR 14 S(O) 2 NR 14 'R 14 '', and -C(CH 3 ) 2 OR 14 is substituted with one or more substituents selected from:

[0280] In a preferred embodiment, the α2δ subunit of a voltage-gated calcium channel, in particular the α2δ-1 subunit, and σ 1 Acts as a dual ligand for the receptor:

[0281] [Table 1]

[0282] [Table 2]

[0283] [Table 3]

[0284] [Table 4]

[0285] [Table 5]

[0286] [Table 6]

[0287] [Table 7]

[0288] [Table 8]

[0289] [Table 9]

[0290] [Table 10]

[0291] [Table 11]

[0292] [Table 12]

[0293] [Table 13]

[0294] [Table 14]

[0295] Optionally, the compound is selected in the form of one of its stereoisomers, preferably enantiomers or diastereoisomers, a racemate, or a mixture of at least two of its stereoisomers, preferably enantiomers and / or diastereoisomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

[0296] Hereinafter, the phrase "compounds of the invention" will be used. These compounds are represented by the general formula (I'), (I 2 '), (I 3 '), (I 4 '), or (I 5') is understood as any compound according to the invention as described above.

[0297] The compounds of the present invention represented by formula (I) above may include enantiomers depending on the presence of chiral centers, or isomers depending on the presence of multiple bonds (e.g., Z, E). Single isomers, enantiomers, or diastereoisomers, and mixtures thereof, are included within the scope of the present invention.

[0298] For clarity, "e.g., R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', R y '''', W, w 1 , w 2 , w 3 , and w 4 is as defined in the Detailed Description below" (as well as the phrase "a compound of formula (I) as defined in any one of claims, e.g. claims 1 to 8" found in the claims) refers to a compound of formula (I) 1 etc. (also from the cited claims) apply. Moreover, this also means that one or more disclaimers or provisos defined in the specification (particularly with respect to the claims) (or used in any of the cited claims, e.g. claim 1) are also applicable to define the respective compound. Thus, for example, a disclaimer or proviso found in claim 1 is also used to define a compound "of formula (I) as defined in the corresponding relevant claim, e.g. any one of claims 1 to 8."

[0299] Generally, the process is described in the experimental section below. Starting materials are either commercially available or can be prepared by conventional methods.

[0300] Preferred embodiments of the present invention are those in which, unless otherwise defined, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', R y '''', W, w 1 , w 2 , w 3 , and w 4 is a process for producing a compound of formula (I), wherein LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate, or triflate).

[0301] In certain embodiments, a process for producing a compound according to formula (I) is provided, comprising the steps of: 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', Ry '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein, W is nitrogen, and the above process produces a compound of formula VIII [ka] of formula IX [ka] with a suitable amine, triethylamine, K, in a suitable solvent, such as acetonitrile or dimethylformamide. 2 CO 3 or N,N-diisopropylethylamine at a suitable temperature comprised between room temperature and reflux, preferably with heating.

[0302] In another particular embodiment, a process for producing a compound according to formula (I) is provided, comprising the steps of: 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein, W is carbon, and the above process produces a compound of formula XIV [ka] The compound of formula XV [ka] with a suitable base such as lithium bis(trimethylsilyl)amide in a suitable solvent such as tetrahydrofuran at a suitable temperature such as room temperature.

[0303] In certain embodiments, in formula R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein, The above process can be repeated when W is nitrogen to give the compound of formula VIII [ka] of formula IX [ka] with a suitable amine, triethylamine, K, in a suitable solvent, such as acetonitrile or dimethylformamide. 2CO 3 or N,N-diisopropylethylamine in the presence of a base, at a suitable temperature comprised between room temperature and reflux, preferably with heating; Or, When W is carbon, the above process can be expressed as formula XIV [ka] The compound of formula XV [ka] with a suitable base such as lithium bis(trimethylsilyl)amide in a suitable solvent such as tetrahydrofuran at a suitable temperature such as room temperature.

[0304] In a particular embodiment, there is a process for producing a compound according to formula (I) by reductive reaction of a carbonyl derivative with a suitable reducing agent, preferably sodium borohydride, in an organic solvent, preferably MeOH, to give a hydroxyl compound.

[0305] In certain embodiments, there is a process for producing a compound according to formula (I) by deprotecting a compound of formula I containing an amine protecting group such as a carbamate, preferably tert-butoxycarbonyl, by any suitable method such as treatment with an acid, preferably HCl or trifluoroacetic acid, in a suitable solvent such as 1,4-dioxane, DCM, ethyl acetate, or a mixture of an organic solvent and water.

[0306] In a particular embodiment, there is a process for producing a compound according to formula (I) by reductive amination reaction of a compound of formula I containing an amino group with an aldehyde, preferably carried out using a reducing agent, preferably sodium triacetoxyborohydride, in an organic solvent, preferably DCE, in the presence of an organic base, preferably DIPEA or TEA. Alternatively, the reaction can be carried out in the presence of an acid, preferably acetic acid.

[0307] In certain embodiments, a process for producing a compound according to formula (I) is provided, comprising the steps of: reacting a base, preferably DIPEA or K, in an organic solvent, preferably acetonitrile, at a suitable temperature, such as in the range of 0-120° C. 2 CO 3

[0023] There is a process by which a compound of formula I containing an amino group is reacted with an alkylating agent in the presence of

[0308] In certain embodiments, there is a process for producing a compound according to formula (I) by reacting a compound of formula I containing an amino group with a vinyl derivative in an organic solvent, preferably 2-methoxyethanol, at a suitable temperature, such as in the range of 20-140° C.

[0309] A particular embodiment of the invention relates to the use of a compound of formula (IIa) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0310] A particular embodiment of the invention relates to the use of a compound of formula (IIb) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0311] A particular embodiment of the invention relates to the use of a compound of formula (III) for preparing a compound of formula (I), H 2 NR 4 III In the formula, R 4 has the meaning defined herein.

[0312] A particular embodiment of the invention relates to the use of a propylmagnesium compound of formula (IV) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0313] A particular embodiment of the invention relates to the use of an allyl derivative of formula (V) for the preparation of a compound of formula (I), [ka] In the formula, R y , R y ', R y '', R y ''', and R y ",'' has the meaning defined herein.

[0314] A particular embodiment of the invention relates to the use of a compound of formula (VI) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R y , R y ', R y '', R y ''', R y '''', W, w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0315] A particular embodiment of the invention relates to the use of a compound of formula (VII) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0316] A particular embodiment of the invention relates to the use of a compound of formula (VIIa) for preparing a compound of formula (I), [ka] In the formula, Y 2 -Y 3 -CHR y ''CHR y '''Ry '''' means R 1 , R 2 , R 3 , R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0317] A particular embodiment of the invention relates to the use of a compound of formula (VIII) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein, and LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate, or triflate).

[0318] A particular embodiment of the invention relates to the use of a butylzinc compound of formula (IX) for preparing a compound of formula (I), [ka] In the formula, R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R7 , R 9 , and R 9 ' has the meaning defined herein.

[0319] A particular embodiment of the invention relates to the use of a compound of formula (XII) for preparing a compound of formula (I), [ka] In the formula, R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , and R 9 ' has the meaning defined herein and Z represents OH or a halogen atom.

[0320] A particular embodiment of the invention relates to the use of a compound of formula (XIII) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0321] A particular embodiment of the invention relates to the use of a compound of formula (XIV) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0322] A particular embodiment of the invention relates to the use of a compound of formula (XV) for preparing a compound of formula (I), [ka] In the formula, R y , R y ', R y '', R y ''', R y "'', has the meaning defined herein, and LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate, or triflate).

[0323] A particular embodiment of the invention relates to the use of a compound of formula (XVI) for preparing a compound of formula (I), [ka] In the formula, R y , R y ', R y'', R y ''', and R y "", has the meaning defined herein, and Z represents OH or a halogen atom.

[0324] A particular embodiment of the invention relates to the use of a compound of formula (XVII) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0325] A particular embodiment of the invention relates to the use of a compound of formula (XVIII) for preparing a compound of formula (I), [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R y , R y ', R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 has the meaning defined herein.

[0326] A particular embodiment of the invention relates to the use of a compound of formula (XIX) for preparing a compound of formula (I), [ka] In the formula, Y 2 -Y 3 -CHR y ''CHR y '''R y '''' means R y '', R y ''', and R y "" has the meaning defined herein.

[0327] A particular embodiment of the invention relates to the use of a compound of formula IIa, IIb, III, IV, V, VI, VII, VIIa, VIII, IX, XII, XIII, XIV, XV, XVI, XVII, XVIII or XIX for the preparation of a compound of formula (I), [ka] [ka] In the formula, Y 2 -Y 3 -CHR y ''CHR y '''R y '''' means R 1 , R 2 , R 3 , R 4 , R 5 , R 5 ', R 5 '', R 5 ''', R 6 , R 6 ', R 6 '', R 6 ''', R 7 , R 9 , R 9 ', R y , R y ', R y '', R y ''', Ry '''', W, w 1 , w 2 , w 3 , and w 4 has the meaning defined herein, LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate, or triflate), and Z represents OH or a halogen atom.

[0328] The resulting reaction products may be purified, if desired, by conventional methods, such as crystallization and chromatography. Where the above-described processes for preparing the compounds of the invention give rise to mixtures of stereoisomers, these isomers can be separated by conventional techniques, such as preparative chromatography. Where chiral centers are present, the compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution.

[0329] One preferred pharmaceutically acceptable form of the compound of the present invention is crystalline form, including this form in pharmaceutical composition.In the case of the salt and also solvate of the compound of the present invention, additional ions and solvent moieties must also be non-toxic.The compound of the present invention may show various polymorphic forms, and it is intended that the present invention encompasses all such forms.

[0330] Another aspect of the present invention relates to a pharmaceutical composition comprising a compound of the present invention as described above according to general formula I, or a pharma- ceutically acceptable salt or stereoisomer thereof, and a pharma- ceutically acceptable carrier, adjuvant, or vehicle. Thus, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a pharma- ceutically acceptable salt or stereoisomer thereof, together with a pharma- ceutically acceptable carrier, adjuvant, or vehicle, for administration to a patient.

[0331] Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions, or emulsions) composition for oral, topical, or parenteral administration.

[0332] In a preferred embodiment, pharmaceutical composition is either solid or liquid oral dosage form.The suitable dosage form for oral administration can be tablet, capsule, syrup or liquid, and can contain conventional excipients known in the art, such as binder, for example, syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; filler, for example, lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; tableting lubricant, for example, magnesium stearate; disintegrant, for example, starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; or pharmaceutically acceptable wetting agent, for example, sodium lauryl sulfate.

[0333] Solid oral compositions can be prepared by conventional methods of mixing, filling or tabletting.Repeated mixing operations can be used to distribute active agent throughout these compositions using large amounts of filler.Such operations are conventional in the art.Tablets can be prepared, for example, by wet or dry granulation, and can be optionally coated, in particular with enteric coating, according to the methods well known in normal pharmaceutical practice.

[0334] The pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions, or lyophilized products in an appropriate unit dosage form. Suitable excipients, such as bulking agents, buffers, or surfactants, may be used.

[0335] The formulations described are prepared using standard methods, such as those described or cited in the Spanish Pharmacopoeia and the US Pharmacopoeia and similar references.

[0336] Administration of the compounds or compositions of the invention may be by any suitable method, such as intravenous injection, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred due to the convenience of the patient and the chronic nature of the disease being treated.

[0337] In general, the effective dosage of a compound of the invention will depend on the relative efficacy of the selected compound, the severity of the disorder being treated, and the weight of the patient. However, active compounds are typically administered one or more times a day, for example 1, 2, 3 or 4 times a day, with typical total daily dosages in the range of 0.1 to 1000 mg / kg / day.

[0338] The compounds and compositions of the invention can be used with other drugs to provide a combination therapy, which may form part of the same composition or may be provided as separate compositions for administration at the same time or at different times.

[0339] Another aspect of the present invention relates to the use of a compound of the present invention or a pharma- ceutically acceptable salt or isomer thereof in the manufacture of a medicament.

[0340] Another aspect of the present invention relates to a compound of the present invention as described above according to general formula I, or a pharma- ceutically acceptable salt or isomer thereof, for use as a medicament for the treatment of pain.Preferably, the pain is moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.This may include mechanical allodynia or thermal hyperalgesia.

[0341] Another aspect of the present invention relates to the use of compounds of the present invention in the manufacture of a medicament for the treatment or prophylaxis of pain.

[0342] In a preferred embodiment, the pain is selected from moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia (preferably also including mechanical allodynia or thermal hyperalgesia).

[0343] Another aspect of the invention relates to a method for treating or preventing pain, comprising administering a therapeutically effective amount of a compound as defined above or a pharmaceutical composition thereof to a patient in need of such treatment. Pain syndromes that may be treated include, inter alia, moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, but may also include mechanical allodynia or thermal hyperalgesia.

[0344] The invention will be explained below with the aid of examples, which are given by way of example only and are not intended to limit the general scope of the invention.

[0345] General Experiment Section Synthesis Description Compounds of formula I can be prepared by a four to five step process as described in Scheme 1, [ka] In the formula, R 1 , R 2 , R 3 , R 4 , R 5-5’’’ , R 6-6’’’ , R 9-9’ , R y-y’’’ ', W, w 1 , w 2 , w 3 , and w 4 has the meaning defined in claim 1, LG represents a leaving group (such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate) and Z represents OH or a halogen atom.

[0346] This process can be carried out as follows.

[0347] Step 1: Compounds of formula IV can be prepared by treating an acid of formula IIa with a suitable amine of formula III in the presence of a suitable coupling agent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate in the presence of a base such as triethylamine in a suitable solvent such as dimethylformamide at a suitable temperature, preferably room temperature. Alternatively, an oxazine derivative of formula IIb may be used as starting material, in which case the reaction with an amine of formula III is carried out in acetonitrile at a suitable temperature, such as by heating.

[0348] Step 2: Compounds of formula VI can be prepared by treating compounds of formula IV with a suitable acid derivative of formula V. When Z is a halogen atom, the reaction can be carried out in the presence of a base such as triethylamine in a suitable solvent such as dichloromethane at a suitable temperature such as room temperature. When Z is OH, the reaction can be carried out using similar conditions as those described in step 1.

[0349] Step 3: Compounds of formula VII can be prepared by treating compounds of formula VI with a suitable halogen, such as iodine, in the presence of a base, such as hexamethyldisilazane, in a suitable solvent, such as dichloromethane, at a suitable temperature, preferably room temperature. Alternatively, the reaction can be carried out with a strong base, such as lithium hydroxide, in a suitable solvent, such as ethylene glycol, at a suitable temperature, such as heating.

[0350] Step 4: Compounds of formula VIII, wherein LG represents a leaving group such as a halogen atom, can be prepared by reacting compounds of formula VII with a suitable halogenating agent such as bromine in the presence of a suitable base such as sodium acetate in a suitable solvent such as acetic acid at a suitable temperature, preferably heating.

[0351] Alternatively, the compound of formula VIII can be prepared by converting the hydroxyl group of the compound of formula XVIII to a leaving group. For example, it can be converted to a triflate group by using trifluoromethanesulfonic anhydride in the presence of a suitable base such as 2,6-lutidine at a suitable temperature such as -78°C to room temperature. The compound of formula XVIII can be obtained from the compound of formula XVII using the conditions described in step 3. XVII can then be prepared by coupling the compound of formula IV with the acid derivative of formula XVI using the conditions described in step 2. Alternatively, the compound of formula XVIII can be obtained from the compound of formula VII using a hydroxylating reagent such as (1R)-1-(((1,2-oxaziridin-2-yl)sulfonyl)methyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one in a suitable solvent such as tetrahydrofuran at a suitable temperature such as cooling to -60°C.

[0352] Step 5: Compounds of formula I, where W is nitrogen, can be prepared by reacting triethylamine, K, in a suitable solvent, such as acetonitrile or dimethylformamide, at a suitable temperature comprised between room temperature and reflux, preferably with heat. 2 CO 3 The compound of formula VIII can be prepared by reacting a compound of formula VIII with a suitable amine of formula IX in the presence of a base such as NH 3 , N,N-diisopropylethylamine, or N,N-diisopropylethylamine. Alternatively, the reaction can be carried out under microwave heating and optionally with an activating agent such as sodium iodide or potassium iodide.

[0353] Alternatively, compounds of formula I, where W is a carbon atom, can be prepared by reacting a compound of formula IV with a compound of formula XII under the conditions used in step 2 (step 2') to give a compound of formula XIII. This may be followed by cyclization under the conditions used in step 3 (step 3') and final alkylation of a compound of formula XIV with a compound of formula XV using a suitable base such as lithium bis(trimethylsilyl)amide in a suitable solvent such as tetrahydrofuran at a suitable temperature such as room temperature (step 4').

[0354] In addition, in the formula, Y 2 -Y 3 -CHR y ''CHR y '''R y Compounds of formula VIIa and R 1 , R 2 , R 3 , R y '', R y ''', R y '''',w 1 , w 2 , w 3 , and w 4 can be prepared by reaction of a compound of formula IIa by treatment with thionyl chloride at a suitable temperature, such as room temperature, followed by addition of a piperidone compound of formula XIX. [ka]

[0355] Additionally, certain compounds of the invention can also be obtained by functional group interconversions across compounds of formula I, or any of the intermediates shown in Scheme 1. The following transformations are examples of possible transformations. Aromatic halogen atoms, i.e. bromine atoms, can be removed by reaction with a base, such as potassium acetate, and Pd(dppf)FeCl in a suitable solvent, such as dioxane, at a suitable temperature, such as heating. 2 The boronic acid derivative can be converted to a suitable boronic derivative by reaction with a bis-pinacol in the presence of a palladium catalyst such as dimethylformamide, and subsequently converted to a hydroxyl group by reaction with sodium perborate in a suitable solvent such as a mixture of tetrahydrofuran and water at a suitable temperature such as room temperature. - Aromatic halogen atoms, i.e. bromine atoms, can be converted to aryl groups by reacting with a suitable arylboronic acid derivative in the presence of a Pd catalyst such as tetrakis(triphenylphosphine)palladium(0) in the presence of a base such as potassium carbonate, in a suitable solvent such as dimethoxyethane-water mixture at a suitable temperature such as heating. - Aromatic halogen atoms, i.e. bromine atoms, can be converted to amino derivatives by reaction with a suitable amine under Buchwald-Hartwig conditions using a Pd catalyst such as tris(dibenzylideneacetone)dipalladium(0) or palladium acetate, and a suitable ligand, preferably a phosphine ligand such as DavePhos, BINAP, or XPhos, with a suitable base such as sodium tert-butoxide or cesium carbonate, in a suitable solvent such as tert-butanol, toluene, or 1,4-dioxane at a suitable temperature, preferably heating. - Aromatic halogen atoms, i.e. bromine atoms, can be converted to alkyl derivatives by reaction with a suitable potassium trifluoroborate derivative using a Pd catalyst such as palladium acetate or bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) and a suitable base such as cesium carbonate in a suitable solvent such as a toluene-water mixture at a suitable temperature, preferably with heating and optionally under microwave irradiation.

[0356] In some of the above processes, it may be necessary to protect reactive or labile groups present with suitable protecting groups (such as, for example, Boc (tert-butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl), or benzyl for the protection of amino groups, and the common silyl protecting groups for the protection of hydroxyl groups). Procedures for introducing and removing these protecting groups are well known in the art and can be found fully explained in the literature.

[0357] Additionally, compounds of formula I can be obtained in enantiopure form by resolution of the racemic compounds of formula I, either by chiral preparative HPLC or by crystallization of diastereomeric salts or co-crystals. Alternatively, the resolution step may be carried out at an earlier stage using any suitable intermediate.

[0358] Compounds of formula IIa, IIb, III, V, IX, XII, XV, XVI, and XIX used in the methods disclosed above are commercially available or may be synthesized according to general procedures described in the literature and exemplified in the synthesis of some of the intermediates. EXAMPLES

[0359] In the examples, the following abbreviations are used: ACN: Acetonitrile AIBN: Azobisisobutyronitrile Aq: Water-based Anh: Anhydrous Chx: Cyclohexane DavePhos: 2-Dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl DCM: dichloromethane DME: Dimethoxyethane DMF Dimethylformamide Eq:Equivalent Et 2 O: Diethyl ether EtOAc; ethyl acetate EtOH: Ethanol h: time HATU: (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) HMDS: Hexamethyldisilazane HPLC: High-performance liquid chromatography KOAc: Potassium acetate LiHMDS: Lithium bis(trimethylsilyl)amide MeOH: Methanol MS: Mass spectrometry Min: Minutes NaOAc: Sodium acetate NaOtBu: Sodium tert-butoxide NBS: N-bromosuccinimide Pd 2 dba 3: Tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)FeCl 2 :[1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) Pd(PPh 3 ) 4 :[Tetrakis(triphenylphosphine)palladium(0) Quant: Quantitative Rt.: Retention time rt: room temperature Sat: Saturation Sol: solution TBAF: Tetrabutylammonium fluoride TEA: Triethylamine TFA: Trifluoroacetic acid THF: tetrahydrofuran TMSCl: Trimethylsilyl chloride XPhos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[0360] The following method was used to determine the HPLC-MS spectra. Method A Column: Aquity UPLC BEH C18 2.1×50 mm, 1.7 μm, flow rate 0.61 mL / min; A:NH 4 HCO 3 10 mM pH 10.6, B:ACN; gradient 98% A for 0.3 min, 98% to 0% A in 2.7 min; isocratic at 0% A for 2 min.

[0361] Method B Column: Acquity UPLC BEH C18 2.1×50 mm, 1.7 μm, flow rate 0.61 mL / min; A:NH 4 HCO 3 10 mM, B:ACN, C:MeOH+0.1% formic acid; gradient 98% A for 0.3 min, 98% A to 0:95:5 A:B:C in 2.7 min; 0:95:5 A:B:C to 100% B in 0.1 min, isocratic at 100% B for 2 min.

[0362] Method C Column: Aquity UPLC BEH C18 2.1×50 mm, 1.7 μm, flow rate 0.61 mL / min; A:NH 4 HCO 3 10 mM, B:ACN; gradient 98% A for 0.3 min, 98% to 0% A in 2.7 min; isocratic at 0% A for 2 min.

[0363] Method D Column Acquity UPLC BEH C18 2.1×50mm, 1.7μm, flow rate 0.60mL / min;A:NH 4 HCO 3 10 mM, B:ACN; gradient 90% A for 0.3 min, 90% A to 5% A in 2.7 min; isocratic 5% A for 0.7 min.

[0364] Method E Column Acquity UPLC BEH C18 2.1×50mm, 1.7μm, flow rate 0.60mL / min;A:NH 4 HCO 3 10Mm pH 10.6, B:ACN; gradient 0.3 min 90% A, 2.7 min 90% A to 5% A; 0.7 min isocratic 5% A.

[0365] Method F Column: Aquity UPLC BEH C18 2.1×50 mm, 1.7 μm, flow rate 0.61 mL / min; A:NH 4 HCO 3 10 mM, B:ACN; gradient 98% A for 0.3 min, 98% A to 100% B in 2.65 min; isocratic at 100% B for 2.05 min.

[0366] Method G Column Acquity UPLC BEH C18 2.1 × 50 mm, 1.7 μm, flow rate 0.6 mL / min; A: water + 0.1% v / v TFA, B: ACN + 0.1% v / v TFA; gradient 95% A to 5% A in 4 min, 5% A to 100B in 0.02 min, isocratic at 100% B in 0.48 min.

[0367] Synthesis of Examples [ka] Example 1. 6-Bromo-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Step a. 2-Amino-5-bromo-N-ethylbenzamide. To a solution of 2-amino-5-bromobenzoic acid (6 g, 28 mmol) in anhydrous DMF (75 mL) under argon atmosphere, TEA (8 mL, 57 mmol) and HATU (13.0 g, 33 mmol) were added and the reaction mixture was stirred at 0° C. for 10 min. Subsequently, ethylamine (2 M in THF, 31 mL, 42 mmol) was added dropwise and the reaction mixture was allowed to reach room temperature and stirred overnight. The reaction crude was dissolved in EtOAc:Et 2 Dilute with HO (1:1) and saturated NaHCO 3 The organic layer was washed with anhydrous Na 2 SO 4 The mixture was dried at 40° C., filtered and concentrated to dryness to give the title compound (7.0 g, yield: 99%).

[0368] Step b. 5-Bromo-N-ethyl-2-pentanamide benzamide. To a solution of the compound obtained in step a (7.0 g, 29 mmol) in anhydrous DCM (120 mL) under an argon atmosphere, TEA (6 mL, 43 mmol) was added dropwise and the mixture was stirred for 10 min. The solution was cooled to 0° C., pentanoyl chloride (4 mL, 33 mmol) was added dropwise, and the reaction mixture was allowed to reach room temperature and stirred overnight. The resulting mixture was diluted with DCM and saturated NaHCO 3 The organic layer was washed with anhydrous Na 2 SO 4 It was dried at 40° C., filtered and the solvent was removed in vacuo to give the title compound (10.0 g, yield: 98%).

[0369] Step c. 6-Bromo-2-butyl-3-ethylquinazolin-4(3H)-one. To a solution of the compound obtained in step b (10.0 g, 30 mmol) in anhydrous DCM (100 mL) was added iodine (15.0 g, 60 mmol) in portions and the mixture was stirred until complete solution was observed. The solution was cooled to 0° C., HMDS (25 mL, 120 mmol) was added dropwise, and the reaction mixture was allowed to reach room temperature and stirred overnight. DCM was added and the reaction mixture was diluted with 5% Na 2 S 2 O 3 The organic layer was washed with anhydrous Na 2 SO 4 Dry at 40° C., filter and remove the solvent in vacuo to give the title compound (9.0 g, yield: 99%).

[0370] Step d. 6-Bromo-2-(1-bromobutyl)-3-ethylquinazolin-4(3H)-one. To a solution of the compound obtained in step c (9.0 g, 28 mmol) in acetic acid (125 mL) was added NaOAc (2.8 g, 34 mmol) slowly and the reaction was stirred at room temperature for 15 min. Bromine (2.2 mL, 42 mmol) was added dropwise and the reaction mixture was heated at 50° C. for 3 h. The mixture was concentrated in vacuo and the residue was dissolved in EtOAc and diluted with 10% NaHSO 3 The organic layer was washed twice with aqueous solution and brine. 2 SO 4 The mixture was dried at rt and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient Chx to Chx:EtOAc (9:1)) to give the title compound (9.2 g, yield: 84%).

[0371] Step e. Title compound. To a solution of the compound obtained in step d (340 mg, 0.876 mmol) in anhydrous ACN (20 mL) was added TEA (0.488 mL, 3.54 mmol) and KI (14.5 mg, 0.088 mmol). The reaction was stirred at room temperature for 20 min and 1-methyl-1,4-diazepane (0.272 mL, 2.19 mmol) was added dropwise. The reaction mixture was heated at 90° C. and stirred overnight. The mixture was concentrated under reduced pressure and the crude residue was dissolved in EtOAc and saturated NaHCO 3The organic layer was washed twice with anhydrous Na 2 SO 4 The crude product was purified by flash chromatography (silica gel, gradient DCM to DCM:MeOH (9:1)) to give the title compound (140 mg, yield: 38%). HPLC-MS(A)Rt, 2.63 min; ESI+-MS m / z:421.0(M+1).

[0372] This method was used to prepare Examples 2-150 using the appropriate starting materials.

[0373] [Table 15]

[0374] [Table 16]

[0375] [Table 17]

[0376] [Table 18]

[0377] [Table 19]

[0378] [Table 20]

[0379] [Table 21]

[0380]

Table 22

[0381]

Table 23

[0382]

Table 24

[0383]

Table 25

[0384]

Table 26

[0385]

Table 27

[0386]

Table 28

[0387]

Table 29

[0388]

Table 30

[0389]

Table 31

[0390]

Table 32

[0391] [Table 33]

[0392] [Table 34]

[0393] [Table 35]

[0394] [Table 36]

[0395] Examples 15 and 16. (R)-3-Ethyl-6-methoxy-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and (S)-3-Ethyl-6-methoxy-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 15 and 16 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0396] Examples 35, 36, 37, and 38. 6-Bromo-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-Bromo-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-Bromo-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, and 6-Bromo-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one. Examples 35, 36, 37, and 38 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0397] Example 66. (R)-2-(1-(1,4-diazabicyclo[3.2.2]nonan-4-yl)butyl)-6-bromo-3-ethylquinazolin-4(3H)-one. Chiral preparative HPLC separation (column LUX C4 21.2×250 mm, 5 μm; temperature: room temperature; eluent: MeOH (0.2% v / v NH3); flow rate: 21 mL / min; Rt1: 4.7 min) was carried out starting from the compound obtained in Example 80 to give the title compound.

[0398] Examples 67, 68, 69, and 70. 6-Bromo-3-ethyl-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 67, 68, 69, and 70 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0399] Examples 73, 74, 75, and 76. 6-chloro-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-chloro-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-chloro-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, and 6-chloro-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one. Examples 73, 74, 75, and 76 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0400] Examples 92, 93, 94, and 95. 6-Bromo-3-ethyl-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((S)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 92, 93, 94, and 95 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0401] Examples 96, 97, 98, and 99. 6-Bromo-3-ethyl-7-fluoro-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-7-fluoro-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-7-fluoro-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-7-fluoro-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 96, 97, 98, and 991 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0402] Examples 101, 102, 103, and 104. 6-Bromo-3-ethyl-2-((S)-1-((S)-6-ethyl-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((R)-6-ethyl-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((R)-6-ethyl-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((R)-1-((S)-6-ethyl-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 101, 102, 103, and 104 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0403] Examples 105, 106, 107, and 108. 6-Bromo-3-ethyl-2-((R)-1-((S)-6-(methoxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((R)-6-(methoxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((S)-6-(methoxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((S)-1-((R)-6-(methoxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 105, 106, 107, and 108 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0404] Examples 109, 110, 111, and 112. 6,7-dichloro-3-ethyl-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6,7-dichloro-3-ethyl-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6,7-dichloro-3-ethyl-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6,7-dichloro-3-ethyl-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 109, 110, 111, and 112 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0405] Examples 113, 114, 115, and 116. 6-bromo-3-ethyl-2-((S)-1-((R)-6-hydroxy-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-bromo-3-ethyl-2-((R)-1-((R)-6-hydroxy-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-bromo-3-ethyl-2-((S)-1-((S)-6-hydroxy-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-bromo-3-ethyl-2-((R)-1-((S)-6-hydroxy-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 113, 114, 115, and 116 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0406] Examples 118, 119, 120, and 121. 6-chloro-3-ethyl-7-fluoro-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-chloro-3-ethyl-7-fluoro-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-chloro-3-ethyl-7-fluoro-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-chloro-3-ethyl-7-fluoro-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 118, 119, 120, and 121 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0407] Examples 123, 124, 125, and 126. 6-Bromo-3-ethyl-2-((R)-1-((S)-6-(hydroxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((R)-6-(hydroxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((R)-6-(hydroxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((S)-1-((S)-6-(hydroxymethyl)-4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 123, 124, 125, and 126 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0408] Examples 127, 128, 129, and 130. 6-bromo-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, 6-bromo-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, 6-bromo-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, and 6-bromo-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one. Examples 127, 128, 129, and 130 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0409] Examples 131, 132, 133, and 134. 6,7-dichloro-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6,7-dichloro-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6,7-dichloro-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, and 6,7-dichloro-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one. Examples 131, 132, 133, and 134 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0410] Examples 135, 136, 137, and 138. 6-chloro-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, 6-chloro-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, 6-chloro-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one, and 6-chloro-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoroquinazolin-4(3H)-one. Examples 135, 136, 137, and 138 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0411] Examples 139, 140, 141, and 142. 6-Bromo-3-ethyl-2-((R)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-Bromo-3-ethyl-2-((S)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-Bromo-3-ethyl-2-((R)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 139, 140, 141, and 142 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0412] Examples 143, 144, 145, and 146. 3-ethyl-6-fluoro-2-((R)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 3-ethyl-6-fluoro-2-((S)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 3-ethyl-6-fluoro-2-((R)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 3-ethyl-6-fluoro-2-((S)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 143, 144, 145, and 146 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0413] Examples 147, 148, 149, and 150. 6-chloro-3-methyl-2-((R)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-chloro-3-methyl-2-((R)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, 6-chloro-3-methyl-2-((S)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one, and 6-chloro-3-methyl-2-((S)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Examples 147, 148, 149, and 150 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0414] Examples 151 and 152. (R)-6-bromo-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and (S)-6-bromo-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Starting from the compound obtained in Example 1, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 80 / 20 / 0.06 v / v / v; flow rate 11 mL / min; Rt1: 6.9 min, Rt2: 10.3 min) to give the title compound.

[0415] Examples 153 and 154. (R)-6-bromo-3-ethyl-2-(1-(4-ethyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and (S)-6-bromo-3-ethyl-2-(1-(4-ethyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Starting from the compound obtained in Example 7, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 95 / 5 / 0.015 v / v / v; flow rate 14 mL / min; Rt1: 6.6 min, Rt2: 7.8 min) was run to give the title compound.

[0416] Examples 155 and 156. (R)-6-bromo-3-ethyl-7-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and (S)-6-bromo-3-ethyl-7-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Starting from the compound obtained in Example 13, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 80 / 20 / 0.06 v / v / v; flow rate 13 mL / min; Rt1: 5.5 min, Rt2: 6.6 min) was run to give the title compound.

[0417] Examples 157 and 158. (R)-2-(1-(1,4-diazepan-1-yl)butyl)-6-bromo-3-ethyl-7-fluoroquinazolin-4(3H)-one and (S)-2-(1-(1,4-diazepan-1-yl)butyl)-6-bromo-3-ethyl-7-fluoroquinazolin-4(3H)-one Starting from the compound obtained in Example 27, a chiral preparative SFC separation (column: Amy C, 20 × 250 mm, 5 μm; temperature: 40 °C; eluent: 40 / 60 EtOH / CO 2 (0.2% v / v NH 3 ); flow rate 50 mL / min; Rt1: 1.5 min, Rt2: 3.0 min) was run to give the title compound.

[0418] Examples 159 and 160. (R)-6-chloro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-3-propylquinazolin-4(3H)-one and (S)-6-chloro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-3-propylquinazolin-4(3H)-one Starting from the compound obtained in Example 23, a chiral preparative SFC separation (column: Chiralpak IG, 20×250 mm, 5 μm; temperature: 40° C.; eluent: 30 / 70 EtOH / CO 2 (0.5% v / v NH 3); flow rate 50 mL / min; Rt1: 2.4 min, Rt2: 2.9 min) to give the title compound.

[0419] Examples 161 and 162. (R)-6-bromo-3-ethyl-8-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and (S)-6-bromo-3-ethyl-8-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Starting from the compound obtained in Example 40, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 97 / 3 / 0.01 v / v / v; flow rate 12 mL / min; Rt1: 9.3 min, Rt2: 12.6 min) to give the title compound. [ka]

[0420] Example 163. 3-Ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one. Step a. 4-Aminonicotinoyl chloride To a solution of 4-aminonicotinic acid (4.02 g, 29 mmol) in toluene (19 mL) under argon atmosphere was added DMF (0.1 mL) and thionyl chloride (21 mL g, 291 mmol) and the reaction mixture was heated at 95° C. for 16 h. The reaction crude was cooled to room temperature and the solvent removed under vacuum and stripped down twice with toluene to give the title compound (4.6 g, quantitative yield).

[0421] Step b. 4-Amino-N-ethylnicotinamide. To a solution of the compound obtained in step a (4.6 g, 29 mmol) in anhydrous ACN (30 mL) was added dropwise ethylamine (2 M in THF, 29 mL, 58 mmol) and TEA (8 mL, 58 mmol) and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed under vacuum and the crude product was dissolved in EtOAc and saturated NaHCO 3 The aqueous layer was extracted with EtOAc, and the combined organic layer was washed with anhydrous Na 2 SO 4 and the solvent was removed in vacuo to give the title compound (2.13 g, yield: 44%).

[0422] Step c N-Ethyl-4-pentanamide nicotinamide. Following the experimental procedure described in step b of example 1 starting from the product obtained in step b (2.13 g, 13 mmol), the title compound was obtained (3.45 g, yield: 99%).

[0423] Step d. 2-Butyl-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one. To a solution of the compound obtained in step c (3.45 g, 12.9 mmol) in anhydrous THF was added TEA (10.8 mL, 77 mmol) and TMSCl (4.08 mL, 32 mmol) dropwise. The reaction mixture was heated at 85° C. for 16 h and NH 4 This was quenched by adding saturated Cl solution. The product was extracted with EtOAc and the combined organic layers were washed with brine and anhydrous Na 2 SO 4 The mixture was dried at 40° C. and filtered. The solvent was removed in vacuo and the crude product was purified by flash chromatography (silica gel, gradient Chx to Chx:EtOAc (4:6)) to give the title compound (1.97 g, yield: 66%).

[0424] Step e. 2-(1-Bromobutyl)-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one. To a solution of the compound obtained in step d (1.09 g, 4.7 mmol) in anhydrous ACN, NBS (1.048 g, 5.88 mmol) and AIBN (77 mg, 0.47 mmol) were added in small portions and the reaction was heated at 95° C. for 2.5 hours. The mixture was allowed to cool to room temperature and dissolved in EtOAc. The organic layer was extracted with Na 2 CO 3 Wash with saturated solution and brine, and add anhydrous Na 2 SO 4 After filtration, the solvent was removed under vacuum to give the title compound, which was used in the next step without further purification (1.4 g, yield: 66%).

[0425] Step f. 3-Ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one. To a solution of the compound obtained in step e (75 mg, 0.24 mmol) in anhydrous ACN, 1-methyl-1,4-diazepane (0.09 mL, 0.73 mmol) was added and the reaction was heated at 50° C. for 16 h. The mixture was allowed to cool to room temperature and dissolved in EtOAc. The organic layer was washed with saturated NaHCO 3 The organic layer was washed with anhydrous Na 2 SO 4 Dry at 40° C., filter, and remove the solvent in vacuo to give the title compound (56 mg, 59% yield). HPLC-MS (B) Rt, 1.49 min; ESI+-MS m / z: 344.2 (M+1).

[0426] This method was used to prepare Examples 164-172 using the appropriate starting materials.

[0427] [Table 37]

[0428] [Table 38]

[0429] Examples 164, 165, 166, and 167. 3-Ethyl-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one, 3-Ethyl-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one, 3-Ethyl-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one, and 3-Ethyl-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one Examples 164, 165, 166, and 167 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0430] Examples 168, 169, 170, and 171. 2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one, 2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one, 2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one, and 2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[4,3-d]pyrimidin-4(3H)-one Examples 168, 169, 170, and 171 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0431] Examples 173 and 174. (R)-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one and (S)-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[4,3-d]pyrimidin-4(3H)-one Starting from the compound obtained in Example 163, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 90 / 10 / 0.03 v / v / v; flow rate 12 mL / min; Rt1: 10.5 min, Rt2: 13.9 min) to give the title compound. [ka]

[0432] Example 175. 6-Bromo-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one. Step a. 2-Amino-5-bromo-N-ethylnicotinamide Starting from 2-amino-5-bromonicotinic acid (2 g, 9.21 mmol), the experimental procedure described in step a of example 1 was followed to give the title compound (2.4 g, yield: quantitative).

[0433] Step b. 6-Bromo-2-butyl-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one. To a solution of the compound obtained in step a (2.4 g, 9.8 mmol) in PPA (12 g) was added pentanoic acid (1.28 mL, 11.8 mmol) dropwise and the reaction was heated at 100° C. for 5 h. The reaction was allowed to cool to room temperature, EtOAc and 10% aqueous NaOH were added, and the crude mixture was stirred at room temperature overnight. The solution was extracted with EtOAc and the combined organic layers were washed with anhydrous Na2 SO 4 It was dried at 40° C., filtered and evaporated in vacuum to give the title compound (3.1 g, yield: 75%).

[0434] Step c, 6-bromo-2-(1-bromobutyl)-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one. Following the experimental procedure described in step d of example 1 starting from the compound obtained in step b (3.1 g, 7.49 mmol), the title compound was obtained (1.85 g, yield: 63%).

[0435] Step d. Title compound Following the experimental procedure described in step e of example 1 starting from the compound obtained in step c (80 mg, 0.21 mmol), the title compound was obtained (15 mg, yield: 17%). HPLC-MS(B)Rt, 1.8 min; ESI+-MS m / z:422.1(M+1).

[0436] This method was used to prepare Examples 176-200 using the appropriate starting materials.

[0437] [Table 39]

[0438] [Table 40]

[0439] [Table 41]

[0440] [Table 42]

[0441] Examples 186, 187, 188, and 189. 6-bromo-2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one, 6-bromo-2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one, 6-Bromo-2-((S)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one and 6-Bromo-2-((S)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylpyrido[2,3-d]pyrimidin-4(3H)-one Examples 186, 187, 188, and 189 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0442] Examples 193, 194, 195, and 196. 3-(cyclopropylmethyl)-6-fluoro-2-((S)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one, 3-(cyclopropylmethyl)-6-fluoro-2-((S)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one, 3-(cyclopropylmethyl)-6-fluoro-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one and 3-(cyclopropylmethyl)-6-fluoro-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one Examples 193, 194, 195, and 196 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0443] Examples 197, 198, 199, and 200. 6-bromo-3-ethyl-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one, 6-bromo-3-ethyl-2-((S)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one, 6-Bromo-3-ethyl-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one and 6-Bromo-3-ethyl-2-((S)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one Examples 197, 198, 199, and 200 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0444] Examples 201 and 202. (R)-3-ethyl-6-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one and (S)-3-ethyl-6-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)pyrido[2,3-d]pyrimidin-4(3H)-one Starting from the compound obtained in Example 182, a chiral preparative HPLC separation (column: Chiralpak AD-H, 20×250 mm, 5 μm; temperature: room temperature; eluent: n-heptane / EtOH / Et 2 NH 95 / 5 / 0.015 v / v / v; flow rate 13 mL / min; Rt1: 11.8 min, Rt2: 14.2 min) to give the title compound. [ka]

[0445] Example 203. 3-Ethyl-6-hydroxy-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. Step a. (3-Ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-4-oxo-3,4-dihydroquinazolin-6-yl)boronic acid. In a Schlenk flask, the compound obtained in Example 1 (221 mg, 0.52 mmol), bis-pinacol (199 mg, 0.78 mmol), KOAc (154 mg, 1.57 mmol), Pd(dppf)FeCl 2 (23 mg, 0.031 mmol) was charged, which was purged and backfilled with argon three times. Under an argon atmosphere, dioxane (5 mL) was added and the reaction mixture was heated at 90° C. for 2 h. The reaction was allowed to cool to room temperature, filtered through Celite, washed with EtOAc, and the solvent was removed in vacuo to give the title compound (189 mg, yield: 27%).

[0446] Step b. Title compound. THF:H 2 To a solution of the compound obtained in step a (36 mg, 0.09 mmol) in 20O (1 mL:0.5 mL) was added sodium perborate (26 mg, 0.032 mmol) and the reaction was stirred at room temperature overnight. The mixture was diluted with EtOAc and extracted twice with EtOAc. The combined organic layers were washed with brine and extracted with anhydrous Na 2 SO 4It was dried at 40° C., filtered and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient DCM to DCM:MeOH (9:1)) to give the title compound (4 mg, yield: 10%). HPLC-MS (B) Rt, 1.57 min; ESI+-MS m / z: 359.4 (M+1). [ka]

[0447] Example 204. 3-Ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-6-phenylquinazolin-4(3H)-one. The compound obtained in Example 1 (64 mg, 0.15 mmol) was placed in a microwave vial, and phenylboronic acid (30 mg, 0.25 mmol), K 2 CO 3 (35 mg, 0.25 mmol), Pd(PPh 3 ) 4 (8 mg, 0.07 mmol), and DME:H 2 A mixture of O (3 mL, 1:1) was added and the reaction mixture was heated at 130 °C for 20 min under MW irradiation (150 W). 3 The combined organic layers were washed with anhydrous Na 2 SO 4 The crude product was purified by flash chromatography (silica gel, gradient DCM to DCM:MeOH (90:10)) to give the title compound (13 mg, yield: 17%). HPLC-MS (B) Rt, 2.23 min; ESI+-MS m / z: 419.3 (M+1).

[0448] This method was used to prepare Example 205 using the appropriate starting materials.

[0449] [Table 43]

[0450] [ka]

[0451] Example 206. 3-Ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-6-((1-methylpiperidin-4-yl)amino)quinazolin-4(3H)-one. The product obtained in Example 1 (75 mg, 0.2 mmol) was added to a Schlenk flask. DavePhos (10 mg, 0.3 mmol), Pd 2 dba 3 (16 mg, 0.02 mmol), and NaO t Bu (68 mg, 0.7 mmol) was added and the mixture was degassed and backfilled with argon. Dioxane (2 mL) (degassed by bubbling argon through the solution for 5 min) and 1-methylpiperidin-4-amine (44 μL, 0.3 mmol) were added and the reaction mixture was heated at 100° C. overnight. The suspension was filtered through Celite, washed with EtOAc and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient DCM to MeOH (100%)) to give the title compound (22 mg, yield: 25%). HPLC-MS (B) Rt, 1.58 min; ESI+-MS m / z: 455.4 (M+1). [ka]

[0452] Example 207. 6-Benzyl-3-ethyl-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one. The product obtained in Example 1 (50 mg, 0.1 mmol) was added to a Schlenk flask. CsF (36 mg, 0.2 mmol), K 2 CO 3 (50, 0.4 mmol), Pd(ddppf)Cl 2(19 mg, 0.02 mmol) was added and the mixture was degassed and backfilled with argon. Dioxane (2 mL) (degassed by bubbling argon through the solution for 5 min) and 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (31 mg, 14 mmol) were added and the reaction mixture was heated at 80° C. overnight. Water was added and the product was extracted with EtOAc. The combined organic layers were washed with anhydrous Na 2 SO 4 The crude product was purified by flash chromatography (Al 2 O 3 , and purified by gradient Chx to Chx:EtOAc (4:1) to give the title compound (14 mg, yield: 28%). HPLC-MS(B)Rt, 2.5 min; ESI+-MS m / z:433.3(M+1). [ka]

[0453] Example 208. 2-(6-bromo-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-4-oxoquinazolin-3(4H)-yl)acetic acid. To a solution of ethyl 2-(6-bromo-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)-4-oxoquinazolin-3(4H)-yl)acetate (obtained according to the procedure described in Example 1, 127 mg, 0.273 mmol) in MeOH (5 mL) was added LiOH (20 mg, 0.819 mmol) at 0° C. The reaction was allowed to reach room temperature and stirred at this temperature overnight. The solvent was removed under vacuum and this was dissolved in 2N NH 3 The title compound was obtained by elution through an SCX column with hexanes to give the title compound (42 mg, yield: 34%). HPLC-MS (B) Rt, 1.58 min; ESI+-MS m / z: 451.2 (M+1). [ka]

[0454] Example 209. (R)-3-Ethyl-6-fluoro-2-(1-(4-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Step a. 2-Amino-N-ethyl-5-fluorobenzamide Starting from 2-amino-5-fluorobenzoic acid (4 g, 26.3 mmol), the procedure described in step a of example 1 was followed to give the title compound (4.9 g, yield: 99%).

[0455] Step b. (S)-N-Ethyl-5-fluoro-2-(2-hydroxypentanamido)benzamide. Following the procedure described in step b of example 1 starting from the compound obtained in step a (4.9 g, 26.3 mmol), the title compound was obtained (7.77 g, yield: 99%).

[0456] Step c. (S)-3-Ethyl-6-fluoro-2-(1-((trimethylsilyl)oxy)butyl)quinazolin-4(3H)-one. To a solution of the compound obtained in step b (7.77 g, 27.3 mmol) in anhydrous DCM (70 mL) was added iodine (13.8 g, 54 mmol) in small portions and the mixture was stirred until the iodine was completely dissolved. HMDS (22 mL, 109 mmol) was then added and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with DCM and washed with saturated Na 2 S 2 O 3 The organic layer was washed with anhydrous Na 2 SO 4 It was dried at 40° C., filtered and concentrated under reduced vacuum to give the title compound (7 g, Yield: 89%).

[0457] Step d. (S)-6-Chloro-2-(1-hydroxybutyl)-3-methylquinazolin-4(3H)-one. To a solution of the compound obtained in step c (7.7 g, 22.8 mmol) in anhydrous THF (125 mL) was added TBAF (1 M in THF, 25 mL, 25 mmol) and the reaction mixture was stirred at 0° C. for 30 min. The mixture was diluted with EtOAc and 2The organic layer was washed with anhydrous NaCl and saturated NaCl solution. 2 SO 4 It was dried at 40° C., filtered and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, gradient Chx to EtOAc) to give the title compound (3.1 g, yield: 52%).

[0458] Step e. Title compound. To a solution of the compound obtained in step d (50 mg, 0.2 mmol) in anhydrous DCM (3 mL) at -78°C, 2,6-lutidine (87 μL, 0.7 mmol) and triflate anhydride (1 M in DCM, 0.24 mL, 0.24 mmol) were added and the mixture was stirred at -78°C for 2 h. A solution of 1-methyl-1,4-diazepane (86 mg, 0.75 mmol) in DMF:DCM (1:1, 0.6 mL) was added and the mixture was allowed to reach room temperature during 4 h. NaHCO 3 The combined organic layers were washed with brine and anhydrous Na 2 SO 4 The mixture was dried at 40° C., filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient DCM to MeOH) to give the title compound (27 mg, yield: 70%). HPLC-MS (B) Rt, 1.96 min; ESI+-MS m / z: 361.3 (M+1).

[0459] This method was used to prepare Examples 210-265 using the appropriate starting materials.

[0460] [Table 44]

[0461] [Table 45]

[0462] [Table 46]

[0463] [Table 47]

[0464] [Table 48]

[0465] [Table 49]

[0466] [Table 50]

[0467] [Table 51]

[0468] Examples 235 and 236. 3-Ethyl-6-fluoro-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-6-fluoro-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 235 and 236 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0469] Examples 237 and 238. 2-((R)-1-((R)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoro-6-methoxyquinazolin-4(3H)-one and 2-((R)-1-((S)-4,6-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethyl-7-fluoro-6-methoxyquinazolin-4(3H)-one Examples 237 and 238 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0470] Examples 239 and 240. 3-Ethyl-5,6-difluoro-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-5,6-difluoro-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 239 and 240 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0471] Examples 241 and 242. 3-Ethyl-6,7-difluoro-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-6,7-difluoro-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 241 and 242 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0472] Examples 243 and 244. 3-Ethyl-7-fluoro-6-methoxy-2-((R)-1-((R)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-7-fluoro-6-methoxy-2-((R)-1-((S)-6-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 243 and 244 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0473] Examples 245 and 246. 6-chloro-3-methyl-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 6-chloro-3-methyl-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 245 and 246 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0474] Examples 250 and 251. 3-Ethyl-6,8-difluoro-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-6,8-difluoro-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 250 and 251 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0475] Examples 254 and 257. 6-chloro-2-((R)-1-((S)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-methylquinazolin-4(3H)-one and 6-chloro-2-((R)-1-((R)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-methylquinazolin-4(3H)-one Examples 254 and 257 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0476] Examples 255 and 256. 6-Fluoro-3-methyl-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 6-Fluoro-3-methyl-2-((R)-1-((S)-5-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 255 and 256 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0477] Examples 258 and 259. 3-Ethyl-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)-6-(trifluoromethyl)quinazolin-4(3H)-one and 3-Ethyl-2-((R)-1-((R)-5-methyl-1,4-diazepan-1-yl)butyl)-6-(trifluoromethyl)quinazolin-4(3H)-one Examples 258 and 259 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0478] Examples 260 and 261. 3-Ethyl-6,7-difluoro-2-((R)-1-((S)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one and 3-Ethyl-6,7-difluoro-2-((R)-1-((R)-3-methyl-1,4-diazepan-1-yl)butyl)quinazolin-4(3H)-one Examples 260 and 261 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min.

[0479] Examples 262, 263, 264, and 265. 6-bromo-2-((R)-1-((S)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-bromo-2-((S)-1-((S)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, 6-bromo-2-((R)-1-((R)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one, and 6-bromo-2-((S)-1-((R)-4,5-dimethyl-1,4-diazepan-1-yl)butyl)-3-ethylquinazolin-4(3H)-one Examples 262, 263, 264, and 265 were directly separated using preparative HPLC: Column: SunFire C18, 10 μm, 19×150 mm; Temperature: 30° C.; Flow rate: 14 mL / min; A: CH 3 CN; B: 10 mM ammonium bicarbonate buffer pH 7; gradient: 5:95 in 8 min + 5:95 in 15 min to 80:20 + 80:20 in 7 min. [ka]

[0480] Example 266. 2-(1-(azepan-4-yl)butyl)-3-ethyl-6-fluoroquinazolin-4(3H)-one. Step a. tert-Butyl 4-(2-((2-(carbamoyl)-4-fluorophenyl)amino)-2-oxoethyl)azepane-1-carboxylate. To a solution of 2-(1-(tert-butoxycarbonyl)azepan-4-yl)acetic acid (0.6 g, 3.29 mmol) in anhydrous DMF (5 mL) under an argon atmosphere, TEA (1.14 mL, 8.2 mmol), HATU (1.5 g, 3.9 mmol), and 2-amino-5-bromo-N-ethylbenzamide (0.847 g, 3.29 mmol) were added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and diluted with NaHCO 3 The combined organic layers were washed with Na 2 SO 4It was dried at 40° C., filtered and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient Chx (100%) to EtOAc (100%)) to give the title compound (1.23 g, yield: 89%).

[0481] Step b. 2-(Azepan-4-ylmethyl)-3-ethyl-6-fluoroquinazolin-4(3H)-one. To a solution of the compound obtained in step a (1.23 g, 2.9 mmol) and iodine (1.48 g, 5.8 mmol) in DCM (50 mL) was added HMDS (2.44 mL, 11.7 mmol) dropwise and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with DCM and diluted with 5% Na 2 S 2 O 3 The organic layer was washed with aqueous solution of Na 2 SO 4 The mixture was dried at rt and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient DCM (100%) to MeOH (100%)) to give the title compound (0.809 g, yield: 91%).

[0482] Step c. tert-Butyl 4-((3-ethyl-6-fluoro-4-oxo-3,4-dihydroquinazolin-2-yl)methyl)azepane-1-carboxylate. To a solution of the compound obtained in step b (0.809 g, 0.226 mmol) in DCM (10 mL) was added TEA (0.743 mL, 5.33 mmol) and di-tert-butyl dicarbonate (0.873 g, 4 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with NaHCO 3 and brine, and the organic layer was washed with Na 2 SO 4 The mixture was dried at 40° C. and filtered. The solvent was removed in vacuum to give the title compound (0.96 g, yield: 89%).

[0483] Step d. tert-Butyl 4-(1-(3-ethyl-6-fluoro-4-oxo-3,4-dihydroquinazolin-2-yl)butyl)azepane-1-carboxylate. To a solution of the compound obtained in step c (0.96 g, 0.23 mmol) in THF (50 mL) under an argon atmosphere, LiHMDS (5.9 mL, 5.9 mmol) was added and the mixture was stirred at −78° C. for 45 min. 1-Iodopropane (2.32 mL, 23.8 mmol) was added and the reaction mixture was stirred at −78° C. for 1 h and at room temperature overnight. The reaction mixture was diluted with EtOAc and NH 4 The organic layer was diluted with water, Na 2 SO 3 The organic layer was washed with anhydrous Na 2 SO 4 The mixture was dried at rt and the solvent was removed under vacuum. The crude product was purified by flash chromatography (silica gel, gradient Chx (100%) to EtOAc (100%)) to give the title compound (0.685 g, yield: 65%).

[0484] Step e. Title compound. To a solution of the compound obtained in step d (0.685 g, 1.53 mmol) in anhydrous DCM (70 mL) was added TFA (2.3 mL) dropwise at 0° C. and the reaction mixture was stirred at room temperature overnight. The mixture was neutralized by adding 20% ​​aqueous NaOH, diluted with DCM and diluted with saturated NaHCO 3 The organic layer was washed with anhydrous Na 2 SO 4 Drying at 40° C., filtering and evaporating to dryness afforded the title compound (451 mg, yield: 85%). HPLC-MS (B) Rt, 1.75 min; ESI+-MS m / z: 346.2 (M+1).

[0485] This method was used to prepare Examples 267-268 using the appropriate starting materials.

[0486] [Table 52]

[0487] [ka]

[0488] Examples 269 and 270. (6S,7R)-2-Bromo-7-ethyl-6-(4-methyl-1,4-diazepan-1-yl)-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one and (6R,7S)-2-Bromo-7-ethyl-6-(4-methyl-1,4-diazepan-1-yl)-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one Step a. 2-Bromo-7-ethyl-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one. To a solution of 2-amino-5-bromobenzoic acid (1.7 g, 1.87 mmol) in anhydrous toluene (30 mL) was added thionyl chloride (5 mL, 39 mmol) at room temperature and the reaction mixture was heated at 80° C. for 2 h. The crude mixture was evaporated under vacuum, 4-ethylpiperidin-2-one (1.0 g, 1.87 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. The crude mixture was evaporated to dryness, dissolved in EtOAc and saturated NaHCO 3 The aqueous phase was extracted with EtOAc, and the organic layer was washed with anhydrous Na 2 SO 4 It was dried at 40° C., filtered and evaporated to dryness. The crude product was purified by flash chromatography (silica gel, gradient Chx to Chx:EtOAc (8:2)) to give the title compound (1.81 g, yield: 75%).

[0489] Step b. 2-Bromo-7-ethyl-6-hydroxy-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one. To a solution of the compound obtained in step a (1.81 g, 5.89 mmol) in anhydrous THF (20 mL) under Ar, LiHMDS (1 M in THF, 6.48 mL, 6.48 mmol) was added dropwise at −78° C. and the reaction mixture was stirred at −78° C. for 3 h. (1R)-1-(((1,2-oxaziridin-2-yl)sulfonyl)methyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one (1.98 g, 7.66 mmol) dissolved in anhydrous THF (15 mL) was added dropwise and the reaction mixture was stirred at −60° C. for 16 h. This was followed by addition of saturated NH4 Cl solution was added and THF was removed under vacuum. The crude mixture was dissolved in EtOAc, washed with water and the organic layer was washed with anhydrous Na 2 SO 4 The crude product was purified by flash chromatography (silica gel, gradient DCM to DCM:MeOH (85:15)) to give the title compound (1.08 g, yield: 56%).

[0490] Step c. Title compound Starting from the compound obtained in step b (300 mg, 0.93 mmol), the experimental procedure described in step e of example 209 was followed to give 2-bromo-7-ethyl-6-(4-methyl-1,4-diazepan-1-yl)-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one (140 mg, yield: 35%). Examples 269 and 270 were separated using preparative HPLC: Column: Chiralpak IG, 5 μm, 20×250 mm; Temperature: room temperature; Eluent: n-heptane / EtOH / Et 2 NH 90 / 10 / 0.3 v / v / v; flow rate: 16mL / min; Rt1: 21.6 min, Rt2: 24.2 min.

[0491] biological activity Pharmacological studies Ca v 2.2 Human α calcium channel 2 δ-1 subunit assay Human alpha 2 δ-1 enriched membranes (2.5 μg) were diluted with 15 nM radiolabeled [ 3H]-gabapentin. NSB (non-specific binding) was measured by adding 10 μM pregabalin. Binding of test compounds was measured either at one concentration (% inhibition at 1 or 10 μM) or at five different concentrations to determine affinity values ​​(Ki). After 60 min incubation at 27° C., binding reactions were terminated by filtration through Multiscreen GF / C (Millipore) presoaked in 0.5% polyethyleneimine in a vacuum manifold station, followed by washing three times with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4. Filter plates were dried for 1 h at 60° C. and radioactivity was read after adding 30 μL of scintillation cocktail to each well. Readings were performed in a Trilux 1450 Microbeta radioactivity counter (Perkin Elmer).

[0492] Human sigma 1 Receptor radioligand assay Transfected HEK-293 membranes (7 μg) were incubated with 5 nM [ 3 H](+)-pentazocine. NBS (non-specific binding) was measured by adding 10 μM haloperidol. Binding of test compounds was measured either at one concentration (% inhibition at 1 or 10 μM) or at five different concentrations to determine affinity values ​​(Ki). Plates were incubated at 37° C. for 120 min. After the incubation period, the reaction mix was then transferred to a MultiScreen HTS, FC plate (Millipore), filtered, and the plate was washed three times with ice-cold 10 mM Tris-HCL (pH 7.4). Filters were dried and counted in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail at approximately 40% efficiency.

[0493] result: The present invention relates to a voltage-dependent calcium channel α 2 δ subunits, and σ 1The present invention aims to provide compounds that act as dual ligands for the receptor, or a series of chemically related compounds, and thus inhibit the α receptor of the voltage-gated calcium channel. 2 δ subunits, and σ 1 Compounds that act as dual ligands for the receptor, particularly those that respond to the following scales: i Highly preferred is an embodiment in which a compound is selected having a bond represented as:

[0494] K i (σ 1 ) is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM.

[0495] K i (α 2 δ-1) is preferably <10000 nM, more preferably <5000 nM, even more preferably <500 nM.

[0496] The following measures are i was adopted to represent binding to the σ1 receptor, expressed as: + K i (σ 1 )>1000nM ++ 500nM<=K i (σ 1 )<=1000nM +++K i (σ 1 )<500nM

[0497] Preferably, K i (σ 1 ) >1000 nM, the following scale was adopted to represent binding to σ1 receptors: + K i (σ 1 )>1000nM, or a range of inhibition between 1% and 50%.

[0498] K i The α of voltage-gated calcium channels expressed as 2 The following scale was adopted to describe binding to the δ-1 subunit: + K i (α 2 δ-1)>5000nM ++ 500nM<=K i (α 2 δ-1) <= 5000nM +++K i (α 2 δ-1)<500nM

[0499] Preferably, K i (α 2 δ-1)>5000nM, α of voltage-dependent calcium channels 2 The following scale was adopted to describe binding to the δ-1 subunit: + K i (α 2 δ-1)>5000nM, 1%-50% inhibition range

[0500] All compounds prepared in this application inhibited the α-terminal domain of the voltage-dependent calcium channel. 2 δ-1 subunit and σ 1 Binding to the receptor is shown, and specifically, the following binding results are shown. σ 1 Receptor and voltage-dependent calcium channel α 2 Table of Examples Including Binding to the δ-1 Subunit:

[0501] [Table 53]

[0502] [Table 54]

[0503] [Table 55]

[0504] [Table 56]

[0505]

Table 57

[0506]

Table 58

[0507]

Table 59

Claims

1. A compound of general formula (I), 【Chemistry 1】 During the ceremony, R ｙ and R ｙ ′ is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, Or, R ｙ and R ｙ ' together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; R ｙ '' is hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, R ｙ ''' and R ｙ "" is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, Or, R ｙ ''' and R ｙ " " together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; W is nitrogen or -CR ｗ -, wherein R ｗ is hydrogen or halogen, Or, R ｗ and R ５ , R ５ ', R ５ '', or R ５ One of the ''s forms a double bond, w1, w2, w3, and w4 are independently selected from the group consisting of nitrogen and carbon; w1, w2, w3, and w4 are all carbon, or one or two of w1, w2, w3, and w4 are nitrogen, while the others are carbon; R １ is hydrogen, halogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, -OR ８ , -NR ８ R ８ ', -NR ８ C(O)R ８ ', -NR ８ C(O)OR ８ ', -C(O)NR ８ R ８ ', -C(O)OR ８ , -OCHR ８ R ８ ', haloalkyl, haloalkoxy, -CN, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; During the ceremony, R ８ and R ８ ′ is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; R ２ is hydrogen, halogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, -OR ２１ , -NO ２ , -NR ２１ R ２１ ', -NR ２１ C(O)R ２１ ', -NR ２１ S (O) ２ R ２１ ', -S(O) ２ N.R. ２１ R ２１ ', -NR ２１ C(O)NR ２１ 'R ２１ '', -SR ２１ , -S(O)R ２１ , -S(O) ２ R ２１ , -CN, haloalkyl, haloalkoxy, -C(O)OR ２１ , -C(O)NR ２１ R ２１ ', -NR ２１ S (O) ２ N.R. ２１ 'R ２１ '', and -C(CH ３ ) ２ OR ２１ is selected from In the formula, R ２１ , R ２１ ', and R ２１ '' are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, R ３ is hydrogen, halogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, -OR ３１ , -NO ３ , -NR ３１ R ３１ ', -NR ３１ C(O)R ３１ ', -NR ３１ S (O) ３ R ３１ ', -S(O) ３ N.R. ３１ R ３１ ', -NR ３１ C(O)NR ３１ 'R ３１ '', -SR ３１ , -S(O)R ３１ , -S(O) ３ R ３１ , -CN, haloalkyl, haloalkoxy, -C(O)OR ３１ , -C(O)NR ３１ R ３１ ', -NR ３１ S (O) ３ N.R. ３１ 'R ３１ '', and -C(CH ３ ) ３ OR ３１ is selected from In the formula, R ３１ , R ３１ ', and R ３１ '' are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ３～６ Alkenyl, and substituted or unsubstituted C ３～６ alkynyl, R ４ is hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylheterocyclyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylcycloalkyl; R ４ and R ｙ together with the nitrogen and carbon atom to which they are attached, respectively, can form a substituted or unsubstituted heterocyclyl of 5 or 6 atoms; R ４ and R ｙ "" together with the nitrogen and carbon atoms to which they are attached, respectively, can form a 6-member substituted or unsubstituted heterocyclyl; R ５ , R ５ ', R ５ '', and R ５ "" is independently hydrogen, halogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, Or, R ５ and R ５ ', and / or R ５ '' and R ５ ''' form a carbonyl group together with the carbon atom to which they are attached, R ６ , R ６ ', R ６ '', and R ６ "" is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, and substituted or unsubstituted C ２～６ alkynyl, R ７ is hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; Or, R ５ and R ５ One of the ' is R ７ Together with -[CH ２ ] ｎ - forming crosslinks, or R ５ '' and R ５ One of the '''s is R ７ Together with -[CH ２ ] ｎ - forming crosslinks, or R ５ and R ５ One of the ' is R ５ '' and R ５ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, or R ５ and R ５ One of the ' is R ６ '' and R ６ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, or R ６ and R ６ One of the ' is R ６ '' and R ６ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, or R ６ and R ６ One of the ' is R ５ '' and R ５ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, or R ９ and R ９ One of the ' is R ７ Together with -[CH ２ ] ｎ - forming crosslinks, or R ９ and R ９ One of the ' is R ６ '' and R ６ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, or R ９ and R ９ One of the ' is R ５ '' and R ５ ''' together with one of -[CH ２ ] ｎ - forming crosslinks, wherein n is 1, 2, or 3; R ９ and R ９ ' are independently hydrogen, halogen, -OR ９１ , substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ selected from the group consisting of alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylheterocyclyl, and substituted or unsubstituted alkylaryl; wherein R 91 is independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, and substituted or unsubstituted C 2-6 alkynyl; Optionally, the compound is in the form of one of the stereoisomers, a racemate or a mixture of at least two of the stereoisomers in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

2. The compound of formula (I) is a compound of formula (I'), 【Chemistry 2】 In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ５ ', R ５ '', R ５ ''', R ６ , R ６ ', R ６ '', R ６ ''', R ７ , R ９ , R ９ ', W, w １ , W ２ , W ３ , and w ４ The compound according to claim 1, wherein:

3. The compound of formula (I) is ２ ') 【Chemistry 3】 In the formula, R １ , R ２ , R ３ , R ４ , R ６ , R ６ ', R ６ '', R ６ ''', R ７ , R ９ , R ９ ', W, w １ , W ２ , W ３ , and w ４ The compound according to claim 1, wherein:

4. The compound of formula (I) is ３’ ), (I ４’ ), or (I ５’ ) 【Chemistry 4】 In the formula, R １ , R ２ , R ３ , R ４ , R ６ , R ６ '', R ７ , R ９ , W, w １ , W ２ , W ３ , and w ４ The compound according to claim 1, wherein:

5. R ７ is hydrogen and substituted or unsubstituted C １～６ The compound according to any one of claims 1 to 4, wherein the aryl group is selected from alkyl.

6. R ７ is hydrogen, while R ６ , R ６ '', and R ９ is substituted or unsubstituted C １～６ The compound of claim 4, which is alkyl.

7. R ７ is substituted or unsubstituted C １～６ alkyl, while R ６ , R ６ '', and R ９ The compound of claim 4 , wherein is hydrogen.

8. R ７ is substituted or unsubstituted C １～６ alkyl, while R ６ , R ６ '', and R ９ is substituted or unsubstituted C １～６ The compound of claim 4, which is alkyl.

9. The compound of formula (I) is ６’ ) or (I ７’ ) 【Chemistry 5】 In the formula, R １ , R ２ , R ３ , R ５ , R ５ ', R ５ '', R ５ ''', R ６ , R ６ ', R ６ '', R ６ ''', R ７ , R ９ , R ９ ', W, w １ , W ２ , W ３ , and w ４ The compound according to claim 1, wherein:

10. The compound of formula (I) is 【Table 1】 【Table 2】 【Table 3】 【Table 4】 【Table 5】 【Table 6】 【Table 7】 【Table 8】 【Table 9】 【Table 10】 【Table 11】 【Table 12】 【Table 13】 【Table 14】 The compound according to any one of claims 1 to 9, selected from:

11. A process for preparing a compound of formula (I) as defined in any one of claims 1 to 9, comprising When W is nitrogen, the compound of formula VIII 【Chemistry 6】 with a compound of formula IX 【Chemistry 7】 in a suitable solvent in the presence of a base at a suitable temperature comprised between room temperature and reflux temperature, Or, When W is carbon, the process is represented by formula XIV 【Chemistry 8】 The compound of formula XV 【Chemistry 9】 with a suitable base in a suitable solvent at room temperature, In the formula, R １ , R ２ , R ３ , R ４ , R ５ , R ５ ', R ５ '', R ５ ''', R ６ , R ６ ', R ６ '', R ６ ''', R ７ , R ９ , R ９ ', R ｙ , R ｙ ', R ｙ '', R ｙ ''', R ｙ "'', w １ , W ２ , W ３ , and w ４ has the meaning as defined in claim 1 for the preparation of a compound of formula (I) as defined in any one of claims 1 to 10, and LG is chloro, bromo, iodo, mesylate, tosylate, nosylate, or triflate.

12. A pharmaceutical composition comprising a compound of formula (I) as defined in any one of claims 1 to 10, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier, adjuvant, or vehicle.

13. A compound of formula (I) as defined in any one of claims 1 to 10 for use as a medicament.

14. A compound of formula (I) as defined in any one of claims 1 to 10 for use as a medicament in the treatment of pain.

15. A compound of formula (I) as defined in claim 14, wherein the pain is moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.

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