Pyrrolopyridine compounds for the treatment of mental illness

Abstract

This disclosure generally relates to compounds, methods for synthesizing them, and their use in the treatment of mental illness or central nervous system disorders.

Description

[Technical Field]

[0001] This application claims priority to Australian Provisional Application No. 2023902053 (filed on 28 June 2023), the entirety of which is incorporated herein by reference.

[0002] This disclosure generally relates to novel compounds, methods for synthesizing them, and their use in the treatment of psychosis or central nervous system disorders. [Background technology]

[0003] Psychosis encompasses many neuropsychiatric disorders that place a significant burden on the lives of those affected. Diagnoses of conditions such as treatment-resistant depression, major depressive disorder, eating disorders, substance abuse disorders, post-traumatic stress disorder, obsessive-compulsive disorder, attention deficit disorder, and schizophrenia can cause devastating symptoms that leave many affected individuals unable to lead normal lives.

[0004] Various serotonergic drugs, including antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors, are marketed to treat psychosis. Unfortunately, in many indications, these medications provide only limited benefit compared to placebo. Additionally, these medications can cause a wide range of side effects, including loss of libido, insomnia, fatigue, and weight gain. Despite their limited efficacy, these drugs continue to be used to treat neuropsychiatric conditions and a wide range of adjunctive medical indications. Since many of these drugs were launched, progress in new treatment options has been limited, and the pharmaceutical industry is under increasing financial pressure to avoid fully emphasizing neuroscience programs. There is a growing unmet need for more effective mental health treatments, and the global COVID-19 pandemic may increase the disease burden worldwide.

[0005] In the 1950s and 1960s, the use of psychedelic drugs to treat various psychotic illnesses was widely studied, and these substances showed promise as treatments for many disorders of the central nervous system (CNS). After decades of prohibition, scientific research into the application of psychedelics as a treatment for psychosis is gaining momentum. The serotonergic psychedelic psilocybin has been designated a Breakthrough Therapy by the FDA for the treatment of major depressive disorder (2019) and treatment-resistant depression (2018). Psilocybin is a prodrug compound produced by many types of mushrooms collectively known as psilocybin mushrooms or “magic mushrooms.” Psilocybin is rapidly metabolized to psilocine, a bioactive compound that results in altered states of consciousness, including altered perception, visual hallucinations, and a distorted sense of space, time, and self. Many patients report mental or “mystical” experiences that have a serious and lasting impact on their mood and behavior. Psilocybin has shown promise in over 50 clinical trials for neuropsychiatric indications, including numerous anxiety disorders, obsessive-compulsive disorder, anorexia nervosa, alcoholism, and nicotine addiction. Psilocybin, along with other psychedelic compounds such as N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), have both immediate and sustained effects on mental states, the latter lasting far beyond the duration of action, likely as a result of their ability to induce increased neuroplasticity in the brain, promote neurogenesis, and increase the spine density of synaptic neurons.

[0006] To date, psilocybin is classified as a controlled substance and / or a drug of abuse in most countries under national drug laws. However, recent clinical research has led to increased awareness of the potential of psychedelic drugs as a breakthrough treatment for CNS disorders, which represent a huge unmet medical need.

[0007] Despite their therapeutic potential, psilocybin and other psychedelics remain designated as abuse drugs in most countries, and the commercial channels for these drugs to the market as medicines are uncertain. As adjuncts to psychotherapy, the long duration of action of psilocybin and LSD makes treatment sessions expensive and impractical for widespread implementation. Despite a long history of safe human use, several adverse events have been reported in clinical trials, including those related to 5-HT 2A Signal transduction bias in (primary target), or, for example, 5-HT 2B This may be due to off-target activity at receptors (cardiac liability antitarget), 5-HT1A (anxiolytic target), or 5-HT2C receptors (e.g., disease-related targets for obesity and some hereditary epilepsy). Spontaneously occurring psychedelics provide important lead structures for a new generation of neurotherapeutic drugs with novel mechanisms of action and / or superior clinical efficacy compared to currently available psychotropic drugs.

[0008] Considering the above, there is a continuing need to develop new compounds that may be useful in treating mental illness or central nervous system disorders.

[0009] Any reference to prior art in this specification does not constitute an endorsement or presentation that the prior art forms part of common general knowledge in any jurisdiction, or that the prior art is understood, considered relevant, and / or can be reasonably expected to be combined with other parts of the prior art by those skilled in the art. [Overview of the project]

[0010] Compounds having potential efficacy in the treatment of psychosis or central nervous system disorders are described in international application PCT / AU2022 / 051591. The compounds described herein are 5HT 2A It exhibits remarkably high activity at serotonin receptors. Preferred compounds also exhibit 5HT 2B and / or 5HT 2CMore selective for 5HT than for serotonin receptors 2A can be surprisingly selective for 5HT 2B and 5HT 2C can be surprisingly selective for 5HT 2A over both serotonin receptors. Also, the compounds described herein can surprisingly have enhanced metabolic stability while retaining the desired activity. Thus, the compounds described herein can also be useful in the treatment of psychiatric or central nervous system disorders.

[0011] In one aspect, the disclosure provides a compound of formula (I):

Chemical formula

[0012] In embodiments of the compound of formula (I), R 1 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R 2 These are, independently, hydrogen and C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 1 and R 2 These, together with the atoms to which they are bonded, form O, S, S(O), SO2, N, and NR. 4 C containing 0, 1, or 2 additional ring heteroparts selected from 3~8 Forms heterocycloalkyl groups, C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R 3 is hydrogen, C 1~6 Alkyl, C 3~8Cycloalkyl, or C 4~14 Selected from alkylene cycloalkyl, Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, C 3~12 Forms heterocycloalkyl groups, C 3~12 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 4 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~7 Selected from heterocycloalkyl groups, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Each R 5 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. One or more substituents R 7 , R 8 , R 9 , R 10 , and R 11 These are, independently, hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each molecule is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. One or more substituents.

[0013] Any compound of formula (I) may be provided in the form of a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug.

[0014] In this embodiment, the compound of formula (I) is none of the following: [ka] [ka] [ka] [ka]

[0015] In this embodiment, the compound of formula (I) is none of the following: [ka]

[0016] In another aspect, the present disclosure provides pharmaceuticals comprising a compound described in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0017] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound described in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, and a pharmaceutically acceptable excipient.

[0018] In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound described in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, an additional therapeutic agent, and a pharmaceutically acceptable excipient.

[0019] In another aspect, the present disclosure relates to a method for treating a disease, disorder, or condition by activating a serotonin receptor, wherein the method involves a compound of formula (I) being applied to a subject requiring it. The present invention provides a method comprising administering a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0020] In another aspect, the Disclosure provides a method for treating a disease, disorder, or condition by activation of serotonin receptors, the method comprising administering to a subject in need thereof a compound of formula (I) as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, in combination with another known agent useful for treating a disease, disorder, or condition by activation of serotonin receptors.

[0021] In another aspect, the Disclosure provides a method for treating mental illness, the method comprising administering to a subject in need of it a compound of formula (I) as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0022] In some embodiments, psychosis is selected from anxiety disorders, depression, mood disorders, psychotic disorders, impulse control and addiction disorders, substance addiction, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), stress response syndromes, dissociative disorders, depersonalization disorders, factitious disorders, sexual and gender disorders, somatic symptom disorders, hallucinations, delusions, psychopathy, and combinations thereof.

[0023] In another aspect, the Disclosure provides a method for treating a disease, disorder or condition of the central nervous system (CNS) and / or a disease, disorder or condition of the nervous system, the method comprising administering to a subject in need of it a compound of formula (I) as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0024] In some embodiments, CNS diseases, disorders, or conditions and / or neurological diseases, disorders, or conditions include neurodevelopmental disorders and neurodegenerative diseases such as Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, Parkinson's disease, and Parkinson's disease-related disorders such as Parkinsonian dementia, corticobasal degeneration, and supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; brittle X syndrome; Angelman syndrome; and genetic disorders. Selected from neurological disorders including ataxia; neuro-otological and oculomotor disorders; neurodegenerative diseases such as retinal amyotrophic lateral sclerosis; tardive dyskinesia; hyperactivity disorder; attention deficit hyperactivity disorder and attention deficit disorder; restless legs syndrome; Tourette syndrome; schizophrenia; autism spectrum disorder; tuberous sclerosis; Rett syndrome; cerebral palsy; reward system disorders including eating disorders such as anorexia nervosa and bulimia nervosa; bulimia nervosa, trichotillomania, dermatopruriticism, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology, as well as combinations thereof.

[0025] In another aspect, the Disclosure provides a method for increasing neuronal plasticity and / or increasing dendritic spine density, the method comprising contacting a neuron with a compound of formula (I) as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, in an amount sufficient to increase neuronal plasticity and / or increase the dendritic spine density of the neuron.

[0026] In another aspect, the present disclosure provides a method for treating weight, comprising administering an effective amount of the compound of the present invention to a subject in need thereof. Treatment of weight may include the treatment of weight gain; weight loss; metabolic disorders; weight gain associated with pharmacokinetic interventions; weight gain associated with psychosis (including those described herein); eating disorders such as anorexia, bulimia, cachexia; eating behaviors; obesity; diabetes mellitus; insulin resistance; prediabetes; glucose intolerance; hyperlipidemia; and cardiovascular disease.

[0027] In another aspect, the Disclosure provides a method for activating serotonin receptors in cells of either a biological sample or a patient, comprising administering a compound of formula (I) as defined in any one of the embodiments disclosed herein to the cells.

[0028] In any embodiment or configuration, the compound of the present invention may be any one of compounds S1 to S42.

[0029] Any embodiment described herein should be applied mutatis mutandis to any other embodiment unless otherwise specified.

[0030] This disclosure should not be limited in scope by the specific embodiments described herein, which are intended to be illustrative only. Functionally equivalent products, compositions, and methods are clearly within the scope of the present invention, as described herein.

[0031] Further aspects of the present invention and further embodiments of the aspects described in the preceding paragraph will become apparent from the following description and are given by example and with reference to the accompanying drawings. [Brief explanation of the drawing]

[0032] [Figure 1] Plasma concentrations of subsets of exemplary compounds P-8, P-5, P-3, and P-1 in male C57BL / 6 mice after IP administration at 10 mg / kg, as described in Example 76. [Figure 2]Time binning and mean ± SD (n=3) HTR counts of subsets of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration over several doses, as described in Example 77. [Figure 3] Temperature results, shown as mean ± SD (n=3) for subsets of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 77. [Figure 4] Spontaneous motility results (total distance) are shown as mean ± SD(n=3) HTR counts for subsets of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration over several doses, as described in Example 77. [Figure 5] Spontaneous motor outcomes (distance / time), expressed as mean ± SD(n=3) HTR counts for subsets of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 77. [Figure 6] Time-fixed results from tail suspension test (TST) experiments described in Example 78 for compounds P-3.2HCl (3 mg / kg, 10 mg / kg) and P-8.2HCl (3 mg / kg, 10 mg / kg, 30 mg / kg) compared to ketamine (10 mg / kg) and vehicle. [Modes for carrying out the invention]

[0033] The present invention, as disclosed and defined herein, will be understood to encompass all alternative combinations of two or more of the individual features mentioned or revealed in the text or drawings. All of these different combinations constitute various alternative embodiments of the present invention.

[0034] definition For the purposes of interpreting this specification, terms used in the singular form also include their plural forms, and vice versa.

[0035] As used herein, unless otherwise required by the context, the term “comprise,” and variations such as “comprising,” “comprises,” and “comprised,” are not intended to exclude further additives, components, integers, or steps.

[0036] The terms “treatment” or “treating” in relation to the subject matter include delaying, slowing, stabilizing, curing, healing, reducing, alleviating, altering, restoring, improving, enhancing, or influencing a disease or condition, its signs or symptoms, or the risk (or susceptibility) to the disease or condition. The term “treating” means any sign of success in treating or improving an injury, condition, or pathology, including any objective or subjective parameters such as reduction; remission; slowing the rate of progression; reducing the severity of the disease; stabilization; reducing signs or symptoms or making the injury more tolerable to the individual; slowing the rate of degeneration or decline; or making the final stage of degeneration less debilitating.

[0037] In particularly preferred embodiments, the methods of the present invention may prevent or alleviate the severity of signs or symptoms of the diseases or conditions described herein, or inhibit or minimize their progression. Therefore, the methods of the present invention have therapeutic and preventive applications.

[0038] As used herein, “prevention” or “prevention” is intended to mean at least reducing the likelihood of acquiring the risk (or susceptibility) to the disease or disability (i.e., preventing at least one of the clinical signs or symptoms of the disease from developing in an individual who may be exposed to or susceptible to the disease but has not yet experienced or shown any signs or symptoms of the disease). Biological and physiological parameters for identifying such patients are provided herein and are well known to physicians.

[0039] In this specification, the terms “subject” and “patient” may be used interchangeably. The terms “individual” and “patient” refer, respectively, to animals treatable by the compounds and / or methods, including, but not limited to, dogs, cattle, horses, sheep, pigs, cattle, and humans and non-human primates. Unless otherwise specified, “subject” or “patient” may include both male and female sexes. Furthermore, this also includes subjects or patients, preferably humans, who are suitable to receive treatment with the pharmaceutical compositions and / or methods of the present invention.

[0040] The term "selective" means higher activity against a first target (e.g., a 5-HT receptor subtype) compared to a second target (e.g., a second 5-HT receptor subtype). In some embodiments, the compound has a selectivity at least 1.25 times, at least 1.5 times, at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 10 times, or at least 100 times higher than the first target compared to the second target. In some embodiments, the compounds described herein are 5-HT 2B and / or 5-HT 2C Preferably 5-HT 2B Compared to one or more other 5-HT receptor subtypes, such as 5-HT 2A It is selective for the receptor. In some embodiments, the compounds described herein are 5-HT 2A and / or 5-HT 2B Preferably 5-HT2B It is selective for the 5-HT2c receptor compared to one or more other 5-HT receptor subtypes.

[0041] When used herein to refer to measurable values ​​such as quantity or duration of time, “about” means to include variations of ±20% or ±10%, in some cases ±5%, in some cases ±1%, and in some cases ±0.1% from a given value, such variations being appropriate for carrying out the disclosed method.

[0042] Scope: Throughout this disclosure, various aspects of the invention may be presented in range form. It should be understood that descriptions in range form are merely for convenience and conciseness and should not be interpreted as inflexible limitations on the scope of the invention. Therefore, range descriptions should be considered to specifically disclose all possible subranges and individual numbers within that range. For example, a range description such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and individual numbers within that range, e.g., 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the range.

[0043] As used herein, the term "alkyl" refers to a linear or branched hydrocarbon radical having 1 to 12 carbon atoms, or any range between them; that is, it contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms. Alkyl alkyl groups are optionally substituted with substituents. As used herein, examples of "alkyl" include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, and isopentyl.

[0044] As used herein, the terms “C1-C2 alkyl,” “C1-C3 alkyl,” and “C1-C6 alkyl” refer to alkyl groups as defined herein, each containing at least one and up to two, three, or six carbon atoms, or any range in between (for example, an alkyl group containing two to five carbon atoms is also within the C1-C6 range).

[0045] The term "alkylene" refers to a linear or branched saturated aliphatic radical having the indicated number of carbon atoms and at least two other groups, i.e., divalent hydrocarbon radicals. The two groups linked to the alkylene may be bonded to the same atom or to different atoms of the alkylene group. For example, a linear alkylene is -(CH2) n It can be a divalent radical, where n is 1, 2, 3, 4, 5, or 6. Typical alkylene groups include, but are not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, pentylene, and hexylene.

[0046] The term "alkenyl," whether used alone or as part of another group, refers to a linear or branched saturated alkylene group, i.e., a saturated carbon chain containing substituents at its two ends. The number of possible carbon atoms in the referenced alkylene group is determined by the prefix "C". n1~n2 This is shown as ". For example, C 2~6 The term alkylene refers to an alkylene group having 2, 3, 4, 5, or 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl(ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexadienyl.

[0047] As used herein, the term “alkynyl” means a linear or branched unsaturated alkynyl group containing at least one triple bond, whether used alone or as part of another group. The number of possible carbon atoms in the referenced alkyl group is determined by the prefix “C n1~n2 This is shown as ". For example, C 2~6 The term alkynyl refers to an alkynyl group having 2, 3, 4, 5, or 6 carbon atoms. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butazinyl, 1-pentynyl, 2-pentynyl, isopentinyl, 1,3-pentadinyl, 1,4-pentadinyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadinyl, 1,4-hexadinyl, 1,5-hexadinyl, 2,4-hexadinyl, or 1,3,5-hexatriinyl.

[0048] The term "cycloalkyl" is intended to include monocyclic, bicyclic, or tricyclic alkyl groups. The number of carbon atoms possible in the referenced cycloalkyl group is determined by the prefix "C". n1~n2 This is shown as ". For example, C 3~8The term cycloalkyl refers to a cycloalkyl group having 3, 4, 5, 6, 7, or 8 carbon atoms. In some embodiments, the cycloalkyl group has 3 to 12, 3 to 10, 3 to 8, 3 to 6, or 3 to 5 carbon atoms in the ring. In some embodiments, the cycloalkyl group has 5 or 6 ring carbon atoms. Examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, the cycloalkyl group has 3 to 8, 3 to 7, 3 to 6, 4 to 6, 3 to 5, or 4 to 5 ring carbon atoms. Bicyclic and tricyclic ring systems include bridging, spiro, and condensed cycloalkyl ring systems. Examples of bicyclic and tricyclic cycloalkyl systems include, but are not limited to, bicyclo[3.1.0]hexanyl, bicyclo[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, adamantyl, and dekalinyl.

[0049] The term "alkylene cycloalkyl" refers to a radical having an alkyl component and a cycloalkyl component, where the alkyl component is linked to the cycloalkyl component at its bonding site. The alkyl component is as previously defined, except that it is at least a divalent alkylene and is linked to the cycloalkyl component and its bonding site. In some cases, the alkyl component may be absent. The alkyl component is C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 It may contain any number of carbon atoms, such as the cycloalkyl components as defined herein. x~y Alkylenecycloalkyl 」The numerical range x to y relates to the total number of alkyl carbons and cycloalkyl ring atoms. Examples of alkylene cycloalkyl groups include, but are not limited to, methylenecyclopropyl, methylenecyclobutyl, methylenecyclopentyl, and methylenecyclohexyl.

[0050] The term "aryl" refers to an aromatic ring system having any preferred number of ring atoms and any preferred number of rings. The number of carbon atoms possible in the referenced aryl group is determined by the prefix "C". n1~n2 This is shown as ". For example, C 6~12 The term "aryl" refers to an aryl group having 6, 7, 8, 9, 10, 11, or 12 carbon atoms. An aryl group may contain any preferred number of ring atoms, e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 ring atoms, as well as 6-10, 6-12, or 6-14 ring members. An aryl group may be monocyclic and may condense to form a bicyclic or tricyclic group, or may be bonded to form a biaryl group. Representative aryl groups include phenyl, naphthyl, and biphenyl. Other aryl groups include benzyl with a methylene linkage. Some aryl groups have 6-12 ring members, such as phenyl, naphthyl, or biphenyl. Other aryl groups have 6-10 ring members, such as phenyl or naphthyl. Some other aryl groups have 6 ring members, such as phenyl.

[0051] The term "alkylene aryl" refers to a radical having an alkyl component and an aryl component, where the alkyl component is linked to the aryl component at its bonding site. The alkyl component is as previously defined, except that the alkyl component is at least a divalent alkylene and is linked to the aryl component and its bonding site. The alkyl component is C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 1~6 , C 2~3 , C 2~4 , C2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 It can contain any number of carbon atoms, such as those listed above. In some cases, the alkyl component may be absent. The aryl component is defined as previously mentioned. "C x~y The numerical range x to y in "alkylenearyl" relates to the total number of alkyl carbons and aryl ring atoms. Examples of alkylenearyl groups include benzyl and ethylenephenyl, but are not limited to these.

[0052] As used herein, the term “alkoxy” refers to an alkyl group as defined herein that is covalently bonded via an O-linking moiety. The alkoxy group is optionally substituted with a substituent. As used herein, examples of “alkoxy” include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, and pentoxy.

[0053] As used herein, the terms “C1-C2 alkoxy,” “C1-C3 alkoxy,” and “C1-C6 alkoxy” refer to alkoxy groups as defined herein, each containing at least one and up to two, three, or six carbon atoms, or any range in between (for example, an alkoxy group containing two to five carbon atoms is also within the C1-C6 range).

[0054] As used herein, the term “alkylamine” refers to an alkyl group as defined herein having one or more amino groups. The amino groups may be primary, secondary, or tertiary. Alkylamines may be further substituted with hydroxyl groups to form an amino-hydroxyl group. Examples of alkylamines include, but are not limited to, ethylamine, propylamine, isopropylamine, ethylenediamine, and ethanolamine. The amino group may be linked to the alkylamine at a bonding site with the rest of the compound, at the omega position of the alkyl group, or linked together with at least two carbon atoms of the alkyl group.

[0055] As used herein, the terms “C1-C2 alkylamine,” “C1-C3 alkylamine,” and “C1-C6 alkylamine” refer to alkylamine groups as defined herein, each containing at least one and up to two, three, or six carbon atoms, or any range in between (for example, an alkylamine group containing two to five carbon atoms is also within the C1-C6 range).

[0056] As used herein, the term “alkylsulfonyl” refers to an alkyl group as defined herein having one or more sulfonyl groups. The sulfonyl groups may be linked to the alkylsulfonyl at a bonding site with the rest of the compound, at the omega position of the alkyl group, or linked together with at least two carbon atoms of the alkyl group.

[0057] As used herein, the terms “C1-C2 alkylsulfonyl,” “C1-C3 alkylsulfonyl,” and “C1-C6 alkylsulfonyl” refer to alkylsulfonyl groups as defined herein, each containing at least one and up to two, three, or six carbon atoms, or any range in between (for example, an alkylsulfonyl group containing two to five carbon atoms is also within the C1-C6 range).

[0058] As used herein, the term “heteroatom” means an atom of any element other than carbon or hydrogen. Examples of heteroatoms include nitrogen, oxygen, sulfur, and phosphorus. Preferred heteroatoms include N, O, and S, preferably N and O.

[0059] As used herein, the term “heteromoite” means a chemical group containing a heteroatom. Examples of heteromoites include O, S, S(O), SO2, N, and NH.

[0060] As used herein, “substituent” refers to a molecular portion covalently bonded to an atom in the molecule of interest. A reference to “substituent” may include a single substituent or one or more substituents from the specified list. In some embodiments, a substituted portion may include one, two, three, four, five, or six substituents, preferably one, two, three, or four, more preferably one, two, or three, one or two, or just one substituent. For example, a “ring substituent” may be a portion such as a halogen, an alkyl group, or any other substituent described herein that is covalently bonded to an atom that is a ring member, preferably a carbon atom or a nitrogen atom. As used herein, the term “substituted” means that, provided that the valence of any one or more hydrogens on the specified atom does not exceed the normal valence of the specified atom, any one of them is replaced by a selection from the specified substituents, and the substitution results in a stable compound, i.e., a compound that can be isolated, characterized, and tested for biological activity.

[0061] Terms such as “optionally substituted” or “substitutable” are used throughout this specification to indicate that a group may or may not be further substituted or condensed with one or more nonhydrogen substituents (to form a polycyclic system). Preferred chemically viable substituents for particular functional groups will be obvious to those skilled in the art.

[0062] Examples of substituents include, but are not limited to, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C3-C7 heterocyclyl, C3-C7 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylsulfanyl, C1-C6 alkylsulfenyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonylamino, arylsulfonoamino, alkylcarboxy, alkylcarboxyamide, oxo, hydroxy, mercapto, amino, acyl, carboxy, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aroyl, aroylamino, heteroaloyl, acyloxy, aroyloxy, heteroaloyloxy, alkoxycarbonyl, nitro, cyano, halo, ureido, and C1-C6 perfluoroalkyl. Preferably, substituents include amino, halo, C1-C6 alkyl, amide, and hydroxyl.

[0063] As used herein, the term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I), and the term "halo" refers to the halogen radicals fluoro(-F), chloro(-Cl), bromo(-Br), and iodine(-I). Preferably, "halo" is fluoro or chloro.

[0064] As used herein, the term “haloalkyl” refers to an alkyl group as defined herein in which one or more (up to all) of the available hydrogen atoms are replaced by halogens. In some cases, the term “perfluoro” can be used to define a compound or radical in which all hydrogens are replaced by fluorine. For example, perfluoromethyl refers to 1,1,1-trifluoromethyl.

[0065] As used herein, the terms “C1-C2 haloalkyl,” “C1-C3 haloalkyl,” and “C1-C6 haloalkyl” refer to haloalkyls as defined herein, each containing at least one and up to two, three, or six carbon atoms, or any range in between (for example, a haloalkyl containing two to five carbon atoms is also within the C1-C6 range).

[0066] For example, the C1 haloalkyl group may be, but is not limited to, a fluoromethyl, difluoromethyl, or trifluoromethyl group.

[0067] As used herein, the term “haloalkenyl” refers to the previously defined alkenyl group in which one or more of the available hydrogen atoms are replaced by halogens. For example, “C 1~6 A "haloalkenyl" (or "C1-C6 haloalkenyl") refers to a previously defined C1-C6 linear or branched alkenyl group having one or more halogen substituents.

[0068] As used herein, the term "haloalkynyl" refers to the previously defined alkynyl group in which one or more of the available hydrogen atoms are replaced by halogens. For example, "C 1~6 A "haloalkynyl" (or "C1-C6 haloalkynyl") refers to a previously defined C1-C6 linear or branched alkynyl group having one or more halogen substituents.

[0069] As used herein, the term haloalkoxy refers to an alkoxy group as defined herein that is substituted with at least one halogen.

[0070] The term "amino" or "amine" refers to the group -NH2.

[0071] The terms "substituted amino" or "secondary amino" refer to amino groups in which hydrogen is substituted with, for example, C1-C6 alkyl groups ("C1-C6 alkylamino"), aryl or aralkyl groups ("arylamino," "aralkylamino"). For example, C1-C3 alkylamino groups such as methylamino (NHMe), ethylamino (NHEt), and propylamino (NHPr) are preferred.

[0072] The terms "disubstituted amino" or "tertiary amino" refer to an amino group in which two hydrogen atoms are substituted with, for example, C1-C6 alkyl groups ("dialkylamino"), aryl and alkyl groups ("aryl(alkyl)amino"), etc., which may or may not be the same. Di(C1-C3 alkyl)amino groups such as dimethylamino (NMe2), diethylamino (NEt2), dipropylamino (NPr2), and their variants (e.g., N(Me)(Et)) are preferred.

[0073] The term "nitro" refers to the group -NO2.

[0074] The terms "cyano" and "nitrile" refer to the group -CN.

[0075] The term "amide" refers to the group -C(O)NH2.

[0076] The term "substituted amide" refers to an amide group in which hydrogen is substituted with, for example, a C1-C6 alkyl group ("C1-C6 alkylamide" or "C1-C6 alkylamide"), an aryl group ("arylamide"), or an aralkyl group ("aralkylamide"). For example, C1-C3 alkylamide groups such as methylamide (-C(O)NHMe), ethylamide (-C(O)NHEt), and propylamide (-C(O)NHPr) are preferred, and this includes their reverse amides (e.g., NHMeC(O)-, -NHEtC(O)-, and -NHPrC(O)-).

[0077] The term "disubstituted amide" refers to an amide group in which two hydrogen atoms are replaced by, for example, a C1-C6 alkyl group ("di(C1-C6 alkyl)amide" or "di(C1-C6 alkyl)amide"), an aralkyl group, or an alkyl group ("alkyl(aralkyl)amide"). For example, di(C1-C3 alkyl)amide groups such as dimethylamide (-C(O)NMe2), diethylamide (-C(O)NEt2), and dipropylamide ((-C(O)NPr2), and their variant forms (e.g., C(O)N(Me)Et), and their inverse amides are also included.

[0078] The term "sulfonyl" refers to the group -SO2H.

[0079] The term "substituted sulfonyl" refers to a sulfonyl group in which hydrogen is substituted with, for example, a C1-C6 alkyl group ("sulfonyl C1-C6 alkyl"), an aryl group ("arylsulfonyl"), or an aralkyl group ("aralkylsulfonyl"). For example, sulfonyl C1-C3 alkyl groups such as -SO2Me, -SO2Et, and -SO2Pr are preferred.

[0080] The terms "sulfonylamido" or "sulfonamide" refer to the group -SO2NH2.

[0081] The terms "substituted sulfonamide" or "substituted sulfonamide" refer to a sulfonylamide group in which hydrogen is substituted with, for example, a C1-C6 alkyl group ("sulfonylamide C1-C6 alkyl"), an aryl group ("aryl sulfonamide"), or an aralkyl group ("aralkyl sulfonamide"). Examples include sulfonylamides such as SO2NHMe, SO2NHEt, and SO2NHPr. 1~C3 alkyl groups are preferred, and include their inverse sulfonamides (e.g., -NHSO2Me, NHSO2Et, and -NHSO2Pr).

[0082] The term "disubstituted sufonamido" or "disubstituted sulfonamide" refers to a sulfonylamide group in which two hydrogen atoms are substituted with C1-C6 alkyl groups ("sulfonylamide di(C1-C6 alkyl)"), aralkyl groups, and alkyl groups ("sulfonamide (aralkyl)alkyl"), which may or may not be the same. For example, sulfonylamide di(C) such as -SO2NMe2, -SO2NEt2, and -SO2NPr2, and their variants (e.g., SO2N(Me)Et). 1~ A C3 alkyl group is preferred, and this includes their inverse sulfonamides (e.g., -N(Me)SO2Me).

[0083] The term "sulfate" refers to the group OS(O)2OH, and includes groups in which hydrogen is replaced by, for example, a C1-C6 alkyl group ("alkyl sulfate"), an aryl group ("aryl sulfate"), or an aralkyl group ("aralkyl sulfate"). For example, C1-C3 alkyl sulfates such as OS(O)2OMe, OS(O)2OEt, and OS(O)2OPr are preferred.

[0084] The term "sulfonate" refers to the group SO3H, and includes groups in which hydrogen is replaced by, for example, C1-C6 alkyl groups ("alkyl sulfonates"), aryl groups ("aryl sulfonates"), aralkyl groups ("aralkyl sulfonates"), etc. For example, SO3Me, SO3Et, and SO3Pr. 1~ C3 alkyl sulfonates are preferred.

[0085] The term “amino acid” as defined herein refers to a portion containing an amino group and a carboxyl group linked by at least one carbon. Amino acids may refer to natural or non-natural amino acids, preferably natural amino acids such as alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Preferably, the amino acid is arginine, lysine, or histidine, most preferably lysine.

[0086] The terms "carboxylate" or "carboxyl" refer to the group -COO- or -COOH.

[0087] The terms "carbamate" or "carbonyl" refer to the group -OC(O)NH2. Carbamates can be substituted with alkyl groups, such as C1-C6 alkyl groups, but are not limited to these, or they can be disubstituted.

[0088] The term "carbonate" refers to the group -OC(O)O- or -OC(O)OH.

[0089] The term "alkyl carbonate" as defined herein refers to a carbonate group in which hydrogen is replaced by, for example, a C1-C6 alkyl group, aryl or aralkyl group ("aryl carbonate" or "aralkyl carbonate"). For example, CO3C1-C3 alkyl groups such as methyl carbonate (CO3Me), ethyl carbonate (CO3Et), and propyl carbonate (CO3Pr) are preferred.

[0090] The term "ester" refers to a hydrogen atom, for example, C 1~This refers to a carboxyl group replaced by a C6 alkyl group ("carboxyl C1-C6 alkyl" or "alkyl ester"), an aryl or aralkyl group ("aryl ester" or "aralkyl ester"). For example, CO2C1-C3 alkyl groups such as methyl esters (CO2Me), ethyl esters (CO2Et), and propyl esters (CO2Pr) are preferred, and this includes their reverse esters (e.g., -OC(O)Me, -OC(O)Et, and -OC(O)Pr).

[0091] The term "heterocyclyl" refers to a part of a heterocyclic compound having 3 to 12 ring atoms (of which 1, 2, 3, 4 or more are ring heteroatoms independently selected from, for example, O, S, and N, or ring heteroatoms selected from, for example, ring heteromolets independently selected from O, S, S(O), SO2, N, and NH) obtained by removing a hydrogen atom from the ring atoms. n1~n2 Alternatively, if it includes "n1~n2", this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, and one or more of the ring atoms, preferably 1, 2, 3, or 4 or more, are replaced by heteroatoms or heteromolets.

[0092] In this context, the prefixes 3, 4, 5, 6, 7, 8, 9, and 10 indicate the number or range of ring atoms, whether carbon atoms or heteroatoms. For example, as used herein, "C 3~10 The terms "heterocyclyl" or "3- to 10-membered heterocyclyl" refer to heterocyclyl groups having 3, 4, 5, 6, 7, 8, 9, or 10 ring atoms. Examples of heterosilyl groups include 5- to 6-membered monocyclic heterocyclyls and 6- to 10-membered bicyclic heterocyclyls (including fusion rings, bridging rings, and spiro-ring systems).

[0093] Examples of monocyclic heterocyclyl groups include those containing one nitrogen atom, such as aziridine (3-membered ring), azetidine (4-membered ring), pyrrolidine (tetrahydropyrrole), pyrroline (e.g., 3-pyrrole, 2,5-dihydropyrrole), 2H pyrrole or 3H pyrrole (isopyrrole, isoazole), or pyrrolidinone (5-membered ring), piperidine, dihydropyridine, tetrahydropyridine (6-membered ring), and azepine (7-membered ring); imidazoline, pyrazolidine (diazolidine), imidazoline, pyrazol Phosphorus (dihydropyrazole) (5-membered ring), piperazine (6-membered ring), and other compounds containing two nitrogen atoms; oxiran (3-membered ring), oxetane (4-membered ring), oxolane (tetrahydrofuran), oxol (dihydrofuran) (5-membered ring), oxane (tetrahydropyran), dihydropyran, pyran (6-membered ring), oxepin (7-membered ring), and other compounds containing one oxygen atom; dioxolane (5-membered ring), dioxane (6-membered ring), and dioxepane (7-membered ring), and other compounds containing two oxygen atoms; trioxy Compounds containing three oxygen atoms, such as san (6-membered ring); compounds containing one sulfur atom, such as thiirane (3-membered ring), thiethane (4-membered ring), thiolane (tetrahydrothiophene) (5-membered ring), thian (tetrahydrothiopyran) (6-membered ring), and thiepane (7-membered ring); compounds containing one nitrogen atom and one oxygen atom, such as tetrahydroxazole, dihydroxazole, tetrahydroisoxazole, dihydroisoxazole (5-membered ring), morpholine, tetrahydrooxazine, dihydrooxazine, and oxazine (6-membered ring). Examples include, but are not limited to, those containing atoms; those containing one nitrogen and one sulfur atom, such as thiazoline, thiazolidinedione (5-membered ring), and thiomorpholine (6-membered ring); those containing two nitrogen and one oxygen atoms, such as oxadiazine (6-membered ring); those containing one oxygen and one sulfur atom, such as oxathiol (5-membered ring) and oxathiane (thioxane) (6-membered ring); and those containing one nitrogen, one oxygen, and one sulfur atom, such as oxathianazine (6-membered ring).

[0094] Heterocyclyls also include heteroaryls (aromatic heterocyclyls) and heterocycloalkyls (non-aromatic heterocyclyls). Such groups may be substituted or unsubstituted.

[0095] The term "aromatic heterocyclyl" can be used interchangeably with the terms "heteroaromatic," "heteroaryl," or "hetalil." The heteroatoms in an aromatic heterocyclyl group can be independently selected from N, S, and O. An aromatic heterocyclyl group may contain one, two, three, or four or more ring heteroatoms. A heteroaryl group may have the prefix C. n1~n2 Alternatively, if it includes "n1~n2", this prefix indicates the number of carbon atoms in the corresponding aryl group, and one or more of the ring atoms, preferably 1, 2, 3, or 4 or more, are replaced by heteroatoms. In the case of condensed aromatic heterocyclyl groups, only one of the rings may contain a heteroatom, and not all rings need to be aromatic.

[0096] In this specification, “heteroaryl” is used to indicate a heterocyclic ring having aromatic properties, and includes aromatic monocyclic ring systems and polycyclic (e.g., bicyclic) ring systems containing one or more aromatic rings. The term aromatic heterocyclil also includes pseudoaromatic heterocyclils. The term “pseudoaromatic” refers to a ring system that is not strictly aromatic but is stabilized by electron delocalization and acts in a similar manner to aromatic rings. Thus, the term aromatic heterocyclil includes polycyclic ring systems in which all fused rings are aromatic, provided that at least one ring is aromatic, as well as ring systems in which one or more rings are nonaromatic. In polycyclic systems containing both aromatic and nonaromatic rings fused together, the groups may be bonded to other parts by aromatic rings or by nonaromatic rings.

[0097] Examples of heteroaryl groups are monocyclic and bicyclic groups containing 5 to 10 ring members. Heteroaryl groups can be, for example, 5- or 6-membered monocyclic rings, or fused 5- and 6-membered rings, or bicyclic structures formed from two fused 6-membered rings, or two fused 5-membered rings. Each ring can typically contain up to about 4 heteroatoms selected from nitrogen, sulfur, and oxygen. Heteroaryl rings contain up to 4 heteroatoms, more typically up to 3 heteroatoms, and more usually up to 2 heteroatoms, for example, a single heteroatom. In one embodiment, the heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atom in the heteroaryl ring can be basic, as in the case of imidazole or pyridine, or it can be essentially non-basic, as in the case of indole or pyrrole nitrogen. Generally, the number of basic nitrogen atoms present in a heteroaryl group, including any amino group substituents of the ring, is less than 5.

[0098] Aromatic heterocyclyl groups can be 5-membered or 6-membered monocyclic aromatic ring systems.

[0099] Examples of five-membered monocyclic heteroaryl groups include, but are not limited to, furanyl, thienyl, pyrrolyl, oxazolyl, oxadiazolyl (including 1,2,3 and 1,2,4 oxadiazolyl and fluzanyl, i.e., 1,2,5-oxadiazolyl), thiazolyl, isoxazolyl, isothiazolyl, pyrazolyl, imidazolyl, triazolyl (including 1,2,3, 1,2,4 and 1,3,4 triazolyl), oxatriazolyl, tetrazolyl, and thiadiazolyl (including 1,2,3 and 1,3,4 thiadiazolyl).

[0100] Examples of six-membered monocyclic heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, triazinyl, pyranyl, oxazinyl, dioxynyl, thiadinyl, and thiadiazinyl. Examples of six-membered aromatic heterocyclyls containing nitrogen include pyridyl (one nitrogen), pyrazinyl, pyrimidinyl, and pyridadinyl (two nitrogens).

[0101] Aromatic heterocyclyl groups can also be bicyclic or polycyclic heteroaromatic ring systems, such as condensed ring systems (including purines, pteridinyl, naphthilidinyl, 1H thieno[2,3-c]pyrazolyl, thieno[2,3-b]furyl, etc.) or linking ring systems (such as oligothiophenes, polypyrroles, etc.). Condensed ring systems may include five-membered or six-membered heterocyclyls condensed to carbocyclic aromatic rings such as phenyl, naphthyl, indenyl, azlenyl, fluorenyl, and anthracenyl, for example, five-membered aromatic heterocyclyls containing nitrogen condensed to a phenyl ring, and five-membered aromatic heterocyclyls containing one or two nitrogens condensed to a phenyl ring.

[0102] Bicyclic heteroaryl groups include, for example, a) a benzene ring fused to a 5-membered or 6-membered ring containing 1, 2, or 3 ring heteroatoms, b) a pyridine ring fused to a 5-membered or 6-membered ring containing 1, 2, or 3 ring heteroatoms, c) a pyrimidine ring fused to a 5-membered or 6-membered ring containing 1 or 2 ring heteroatoms, d) a pyrrole ring fused to a 5-membered or 6-membered ring containing 1, 2, or 3 ring heteroatoms, e) a pyrazole ring fused to a 5-membered or 6-membered ring containing 1 or 2 ring heteroatoms, f) an imidazole ring fused to a 5-membered or 6-membered ring containing 1 or 2 ring heteroatoms, g) an oxazole ring fused to a 5-membered or 6-membered ring containing 1 or 2 ring heteroatoms. h) an isoxazole ring condensed on a five-membered or six-membered ring containing one or two ring heteroatoms; i) a thiazole ring condensed on a five-membered or six-membered ring containing one or two ring heteroatoms; j) an isothiazole ring condensed on a five-membered or six-membered ring containing one or two ring heteroatoms; k) a thiophene ring condensed on a five-membered or six-membered ring containing one, two, or three ring heteroatoms; l) a furan ring condensed on a five-membered or six-membered ring containing one, two, or three ring heteroatoms; m) a cyclohexyl ring condensed on a five-membered or six-membered ring containing one, two, or three ring heteroatoms; and n) a cyclopentyl ring condensed on a five-membered or six-membered ring containing one, two, or three ring heteroatoms.

[0103] Specific examples of bicyclic heteroaryl groups containing a five-membered ring fused to another five-membered ring include, but are not limited to, imidazothiazole (e.g., imidazo[2,1-b]thiazole) and imidazoimidazole (e.g., imidazo[1,2-a]imidazole).

[0104] Specific examples of bicyclic heteroaryl groups containing a six-membered ring condensed onto a five-membered ring include, but are not limited to, benzofuran, benzothiophene, benzimidazole, benzoxazole, isobenzoxazole, benzisoxazole, benzothiazole, benzisothiazole, isobenzofuran, indole, isoindole, indidine, indoline, isoindoline, purines (e.g., adenine, guanine), indazole, pyrazolopyrimidine (e.g., pyrazolo[1,5-a]pyrimidine), benzodioxol, and pyrazolopyridine (e.g., pyrazolo[1,5-a]pyridine) groups. Further examples of six-membered rings condensed onto a five-membered ring include pyrrolopyridine groups such as the pyrrolo[2,3-b]pyridine group.

[0105] Specific examples of bicyclic heteroaryl groups containing two fused six-membered rings include, but are not limited to, quinoline, isoquinoline, chroman, thiochroman, chromene, isochromene, isochroman, benzodioxane, quinolidine, benzoxazine, benzodiazine, pyridopyridine, quinoxaline, quinazoline, sinnoline, phthalazine, naphthyridine, and pteridine groups.

[0106] Examples of heteroaryl groups containing aromatic and non-aromatic rings include tetrahydronaphthalene, tetrahydroisoquinoline, tetrahydroquinoline, dihydrobenzothiophene, dihydrobenzofuran, 2,3-dihydro-benzo[1,4]dioxin, benzo[1,3]dioxol, 4,5,6,7-tetrahydrobenzofuran, indoline, isoindoline, and indane groups.

[0107] Therefore, examples of aromatic heterocycles fused to carbocyclic aromatic rings include, but are not limited to, benzothiophenyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzimidazolyl, indazolyl, benzoxazolyl, benzisoxazolyl, isobenzoxazoyl, benzothiazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, synnolinyl, benzotriazinyl, phthalazinyl, and carboninyl.

[0108] The terms "heterocycloalkyl" or "non-aromatic heterocyclyl" encompass optionally substituted saturated and unsaturated rings containing at least one heteroatom such as N, S, and O, or a heteromoty such as O, S, S(O), SO2, N, and NH. The ring may contain one, two, three, four or more heteroatoms or heteromotyties. Heterocycloalkyl groups are prefixed with C. n1~n2 Or, if it includes "n1~n2", this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, and one or more of the ring atoms, preferably 1, 2, 3, or 4 or more, are replaced by heteroatoms or heteromolets. The ring may be a monocyclic ring or part of a polycyclic ring system. Examples of polycyclic ring systems include fused rings and / or bridging rings and spiro rings. Not all rings in a non-aromatic heterocyclic polycyclic ring system must contain heteroatoms, however at least one ring contains one or more heteroatoms.

[0109] Non-aromatic heterocyclyls can be monocyclic rings with 3 to 8 members.

[0110] Examples of five-membered non-aromatic heterocyclyl rings include 2H-pyrrolyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidinyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrazolinyl, 2-pyrazolinyl, 3-pyrazolinyl, pyrazolidinyl, 2-pyrazolidinyl, 3-pyrazolidinyl, imidazolidinyl, 3-dioxolanil, thiazolidinyl, isoxazolidinyl, and 2-imidazolinyl.

[0111] Examples of 6-membered non-aromatic heterocyclines include piperidinyl, piperidinonyl, pyranyl, dihildopyranyl, tetrahydropyranyl, 2Hpyranyl, 4Hpyranyl, thianyl, thianyl oxide, thianyl dioxide, piperazinyl, diozanil, 1,4-dioxynyl, 1,4-dithianyl, 1,3,5-triozalanyl, 1,3,5-trithianyl, 1,4-morpholinyl, thiomorpholinyl, 1,4-oxathianyl, triazinyl, and 1,4-thiadinyl.

[0112] Examples of 7-membered non-aromatic heterocyclines include azepanil, oxepanil, and thiepanil.

[0113] Non-aromatic heterocyclyl rings can also be bicyclic heterocyclyl rings, such as linking ring systems (e.g., uridinyl) or fused ring systems. Examples of fused ring systems include non-aromatic 5-membered, 6-membered, or 7-membered heterocyclyls fused to carbocyclic aromatic rings such as phenyl, naphthyl, indenyl, azlenyl, fluorenyl, and anthracenyl. Examples of non-aromatic 5-membered, 6-membered, or 7-membered heterocyclyls fused to carbocyclic aromatic rings include indolinyl, benzodiazepinyl, benzazepinyl, and dihydrobenzofuranyl.

[0114] The term "alkylene heteroaryl" refers to a radical having an alkyl component and a heteroaryl component, where the alkyl component is linked to the heteroaryl component at the bonding site. The alkyl component is as previously defined, except that it is at least a divalent alkylene and is linked to the heteroaryl component and the bonding site. In some cases, the alkyl component may be absent. The alkyl component is C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 It may contain any number of carbon atoms, such as the heteroaryl components as defined herein. x~y Alkylenecycloalkyl 」 The numerical range x to y is related to the total number of alkyl carbons and heteroaryl ring atoms (combinations of carbon and heteroatoms).

[0115] The term "alkylene heterocycloalkyl" refers to a radical having an alkyl component and a heterocycloalkyl component, where the alkyl component is linked to the heterocycloalkyl component at the bonding site. The alkyl component is as previously defined, except that it is at least a divalent alkylene and is linked to the heterocycloalkyl component and the bonding site. In some cases, the alkyl component may be absent. The alkyl component is C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C4~6 , and C 5~6 It may contain any number of carbon atoms, such as the heterocycloalkyl components as defined herein. x~y The numerical range x to y in "alkylene heterocycloalkyl" is related to the total number of alkyl carbons and heterocycloalkyl ring atoms (combinations of carbon and heteroatoms).

[0116] As used herein, the term solvate refers to a complex of a compound with either a stoichiometric or non-stoichiometric amount of solvent. Solvates are often formed during crystallization processes using pharmaceutically acceptable solvents such as water and ethanol. Hydrates are formed when the solvent is water, or alkoxides are formed when the solvent is alcohol.

[0117] As used herein, the term polymorphism refers to different crystal packing arrangements of a compound with the same elemental composition. Polymorphisms typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, optical and electrical properties, stability, and solubility. The single-crystal morphology may be dominant depending on various factors such as the recrystallization solvent, crystallization rate, and storage temperature.

[0118] As used herein, the term “metabolite” refers to a derivative of a compound formed when a compound is metabolized. The term “active metabolite” refers to a biologically active derivative of a compound formed when a compound is metabolized. As used herein, the term “metabolized” refers to the total process by which a particular substance is altered by an organism (including, but not limited to, hydrolysis and enzyme-catalyzed reactions). Thus, enzymes can cause specific structural changes in a compound. Metabolites of compounds disclosed herein are optionally identified by either administration of the compound to a host and analysis of tissue samples from the host, or by incubation of the compound using hepatocytes in vitro and analysis of the resulting compound.

[0119] The definitions and conventions of stereochemistry used herein generally follow SP. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984), McGraw-Hill Book Company, New York, and Eliel, E. and Wilen, S., “Stereochemistry of Organic Compounds”, John Wiley & Sons, Inc., New York, 1994. The compounds of the present invention may contain asymmetric or chiral centers and therefore exist in different stereoisomer forms. The term “stereoisomer” refers to compounds that have the same chemical composition but differ with respect to the arrangement of atoms or groups in space. As used herein, the term “stereoisomer” includes, but is not limited to, diastereomers, enantiomers, and atropisomers, as well as mixtures thereof such as racemic mixtures.

[0120] As used herein, the term “pharmaceutically acceptable salt” refers to a salt that, within the bounds of sound medical judgment, is suitable for use in contact with human and lower animal tissues without excessive toxicity, irritation, or allergic reactions, and is commensurate with a reasonable benefit / risk ratio. pharmaceutically acceptable salts are well known in the art. For example, SMBerge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences 1977, 66, 1-19, which is incorporated herein by reference. Examples of pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts of amino groups formed using inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or using organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipine, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, and 2-hydroxyethansulfate. Examples include honate, lactobionate, lactate, lauric acid, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, and valerate.

[0121] compound This disclosure is based on formula (I): [ka] A compound of, During the ceremony, R 1 and R 2 However, each independently, hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8Cycloalkyl, C 4~14 Alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, and one or two ring hetero moieties selected from O, S, N, S(O), SO2, and NR 4 Each is further optionally substituted with one or more substituents independently selected from C 3~6 Heterocycloalkyl containing Alternatively, R 1 And R 2 Together with the nitrogen atom to which they are attached form a C 4 Heterocycloalkyl containing zero, one or two additional ring hetero moieties selected from O, S, S(O), SO2, N, and NR 3~8 To form Said C 3~8 Heterocycloalkyl is halogen, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R 3 However, hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 Selected from alkylene cycloalkyl, Alternatively, R 3 , and R 1 and R 2 One of them, together with the atom to which they are bonded, C 3~12 Forms heterocycloalkyl groups, C 3~12 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 4 However, independently, hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C with one or two ring hetero moieties selected from O, S, S(O), SO2, N, and NR 5 Selected from heterocycloalkyl, 3~7 The C The C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is each optionally substituted with one or more substituents independently selected from halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 Selected independently from, The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is further optionally substituted with one or more substituents independently selected from (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, and C with one or two ring hetero moieties selected from O, S, S(O), SO2, N, and NR 5 Selected from heterocycloalkyl, 3~6 Each is further optionally substituted with one or more substituents independently selected from, Each R 5 Is independently hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R 7 , R 8 , R 9 , R 10 , and R 11 However, each is independent of hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 However, independently, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Or, X 2 CR 7 If R 7 , and R 1 , R 2 or R 3 One of them combines with the atom to which they are bonded, C5~8 Forms heterocycloalkyl groups, C 5~8 Heterocyclylalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 SO2R 14 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Or, X 1 NR 6 X 2 CR 7 If R 6 and R 7 However, when these are combined with the atoms to which they are bonded, C 4~10 Heterocycloalkyl or C 5~10 Forms a heteroaryl, C 4~10 Heterocycloalkyl and C 5~10 Heteroaryls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 SO2R 14 , C 1~6 Alkyl, C 1~6Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Or, Z 1 CR 8 And Z 2 CR 9 If Z 2 CR 9 And Z 3 CR 10 If Z 3 CR 10 And Z 4 CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 However, when these are combined with the atoms to which they are bonded, C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 Forms a heteroaryl, C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 SO2R 14 , C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 14 However, independently, hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NO2, NHCH3, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6The present invention provides compounds, or pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs thereof, each optionally substituted with one or more substituents independently selected from heterocycloalkyl groups.

[0122] In some embodiments, R 8 and R 9 (If any) one of them is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl and C 1~6 One is selected from a haloalkyl group, and the other (if present) is hydrogen.

[0123] In some embodiments, R 8 (If present) halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl and C 1~6 Selected from haloalkyl, R 9 If present, it is hydrogen.

[0124] In some embodiments, R 9 (If present) halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl and C 1~6 Selected from haloalkyl, R 8 If present, it is hydrogen.

[0125] In some embodiments, R 8 (If present) halogen, OR 13 , and C 1~6 Selected from alkyl, R 9 If present, it is hydrogen.

[0126] In some embodiments, R 9 (If present) halogen, OR 13, and C 1~6 Selected from alkyl, R 8 If present, it is hydrogen.

[0127] In some embodiments, R 8 and R 9 One of them is OR 13 That is the case.

[0128] Several embodiments, each R 13 (If present), independently, hydrogen and C 1~6 Selected from alkyl groups.

[0129] In some embodiments, each R 13 If it exists, then it is H.

[0130] In some embodiments, each R 13 (If present) C 1~6 Alkyl, preferably C 1~4 Alkyl, more preferably methyl.

[0131] In some embodiments, R 7 If present, it is hydrogen.

[0132] In some embodiments, R 8 If present, it is hydrogen.

[0133] In some embodiments, R 9 If present, it is hydrogen.

[0134] In some embodiments, R 10 If present, it is hydrogen.

[0135] In some embodiments, R 7 and R 8 If present, it is hydrogen.

[0136] In some embodiments, R 7 and R 10If present, it is hydrogen.

[0137] In some embodiments, R 8 and R 10 If present, it is hydrogen.

[0138] In some embodiments, R 7 , R 8 , and R 10 If present, it is hydrogen.

[0139] In some embodiments, R 8 , R 9 , and R 10 Only one of them is not hydrogen. In some embodiments, R 8 , R 9 , and R 10 R 8 Only is it other than hydrogen. In some embodiments, R 8 , R 9 , and R 10 R 9 Only is it other than hydrogen. In some embodiments, R 8 , R 9 , and R 10 R 10 Only the element other than hydrogen is present.

[0140] In some embodiments, R 1 and R 2 At least one of them is not methyl. In some embodiments, R 1 and R 2 Neither of them is methyl.

[0141] In some embodiments, R 1 and R 2 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 1 and R 2 These combine with the atoms to which they are bonded to form O, S, S(O), SO2, N, and NR 4 C containing 0, 1, or 2 additional ring heteroparts selected from 3~8 Forms heterocycloalkyl groups, C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R 3 is hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14Selected from alkylene cycloalkyl, Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, C 3~12 Forms heterocycloalkyl groups, C 3~12 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 4 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~7 Selected from heterocycloalkyl groups, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Each R 5 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 7 , and R 1 , R 2 or R 3 One of them, when combined with the atom to which they are bonded, becomes C 5~8 Forms heterocycloalkyl groups, C 5~8 Heterocyclylalkyls are halogens, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 SO2R 14 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R 8 , R 9 , and R 10 These are, independently, hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 8 and R 9 , or R 9 and R 10 These combine with the atoms to which they are bonded, C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 Forms a heteroaryl, C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 SO2R 14 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 14 These are, independently, hydrogen and C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NO2, NHCH3, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each molecule is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group.

[0142] In some embodiments, R 1 and R 2 Each of them is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 Selected from alkylenecycloalkyl groups.

[0143] In some embodiments, R 1 and R 2 C 1~4 Each alkyl group is selected independently.

[0144] In some embodiments, R 1 and R 2 These, together with the nitrogen they are bound to, result in the following: [ka] It forms one of the following.

[0145] In some embodiments, R 1 and R 2 These combine with the atoms to which they are bonded, C 3~6 Forms a heterocycloalkyl group, and the C 3~6 Heterocycloalkyls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 and SO2R 4 , (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from3~6 It is optionally substituted with one or more substituents independently selected from heterocycloalkyl groups, where R 4 This is defined in one of the paragraphs mentioned above.

[0146] In some embodiments, R 3 It is hydrogen.

[0147] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, C 3~8 Forms a heterocycloalkyl group, and the C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups, where R 4 This is defined in one of the paragraphs mentioned above.

[0148] In some embodiments, R 7 , R 8 , R 9 , and R 10 These are, independently, hydrogen, halogen, CN, OR 13 , N(R13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. In the formula, R13 This is defined in one of the paragraphs mentioned above.

[0149] In some embodiments, R 7 , R 8 , R 9 , and R 10 These are, independently, hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 SO2R 13 , N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 It is optionally substituted with one or more substituents independently selected from alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NO2, NHCH3, SH, SCH3, SO2CH3, and SOCH3. C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. In the formula, R 13 This is defined in one of the paragraphs mentioned above.

[0150] In some embodiments, R 7, R 8 , R 9 , and R 10 One or two of these are, independently, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 Selected from, in the formula, R 13 C 1~6 Alkyl and C 1~6 Selected from haloalkyl, R 7 , R 8 , R 9 , and R 10 The other of each is hydrogen.

[0151] Further Embodiments In the embodiment, the compound of the present invention is of formula (I): [ka] It is a compound of the formula, in which, R 1 However, independently, hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R 2 However, independently, hydrogen, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 1 and R 2 However, together with the atoms to which these are bonded, they form O, S, S(O), SO2, N, and NR 4 C containing 0, 1, or 2 additional ring heteroparts selected from 3~8 Forms heterocycloalkyl groups, C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R 3 However, hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 Selected from alkylene cycloalkyl, Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, C 3~12 Forms heterocycloalkyl groups, C3~12 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 4 However, independently, hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~7 Selected from heterocycloalkyl groups, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl sulfonyl, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl groups are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Each R 5 However, independently, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. One or more substituents R 7 , R 8 , R 9 , R 10 , and R 11 However, each is independent of hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13, S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 However, independently, hydrogen, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls, halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each molecule is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group.

[0152] In this embodiment, the compound of formula (I) is none of the following: [ka]

[0153] In some embodiments, R 7 H is R 8 H is R 10 is H. In these embodiments, the compound is of formula (II): [ka] It may be provided by, in the formula, R 1 , R 2 , R 3 , and R 9 However, this is as defined in any aspect or embodiment of this specification.

[0154] R1 , R 2 , and R 3 In this embodiment, R 1 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R 2 These are, independently, hydrogen and C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R 1 and R 2 These, together with the atoms to which they are bonded, form O, S, S(O), SO2, N, and NR. 4 C containing 0, 1, or 2 additional ring heteroparts selected from 3~8 Forms heterocycloalkyl groups, C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. In this embodiment, R 1 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the heterocycloalkyl groups is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group.

[0155] In this embodiment, R 1 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Selected from haloalkyl groups, C 1~6 Alkyl, C 1~6 Haloalkyls are halogens, CN, and C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4, C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents that are independently selected from the original molecule.

[0156] In this embodiment, R 2 Independently, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 , and SO2R 4 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C 6~12Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring heteroparts selected from 3~6 Each of the heterocycloalkyl groups is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group.

[0157] In this embodiment, R 1 and R 2 At least one of them is not hydrogen.

[0158] In this embodiment, R 1 and R 2 Neither of them is hydrogen. In the embodiment, R 1 and R 2 None of them are hydrogen.

[0159] In this embodiment, R 1 and R 2 These, together with the atoms to which they are bonded, form O, S, S(O), SO2, N, and NR. 4 C containing 0, 1, or 2 additional ring heteroparts selected from 3~8 Forms heterocycloalkyl groups, C 3~8 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups.

[0160] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form O, S, S(O), SO2, N, and NR. 4 C containing 0 or 1 additional ring heteroparts selected from 4~8 Forms a heterocycloalkyl group, C 4~8 Heterocycloalkyls are halogens, C 1~8 Alkoxy, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is optionally substituted with one or more substituents selected from heterocycloalkyl groups.

[0161] In this embodiment, R 1 and R 2 These, together with the nitrogen atom to which they are bonded, are optionally substituted with C 4~8 It forms a heterocycloalkyl. In these embodiments, the compound of formula (I) is of formula (III). [ka] It may be provided as a compound of the formula, in which, R 3 and R9 However, as defined in any aspect or embodiment of this specification, n is an integer between 1 and 5, preferably 1, 2, or 3. Each R may be the same or different, independently of hydrogen, halogen, and C. 1~8 Alkoxy, C 1~6 Alkyl, C 1~6 Haloalkyl, C 3~6 Cycloalkyl, and C 3~6 C is a heterocycloalkyl group, or a group to which two R atoms are optionally substituted together with the atom to which they are bonded. 4~12 They can form cycloalkyl or optionally substituted 4- to 12-membered heterocycloalkyl rings, and thus condensed, spiro, or bridging cyclic systems. In the embodiment, two Rs bonded to the same ring carbon atom are optionally substituted C 4~12 A spirocyclic ring system is formed by creating a cycloalkyl or optionally substituted 4- to 12-membered heterocycloalkyl ring. Preferably, the two R atoms bonded to the same ring carbon atom are optionally substituted C 4~6 A spirocyclic ring system is formed by creating a cycloalkyl or optionally substituted 4- to 6-membered heterocycloalkyl ring.

[0162] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, do not contain additional ring heteromones. 4~8 It forms a heterocycloalkyl group.

[0163] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form monocyclic or fused bicyclic carbon atoms. 4~8 It forms a heterocycloalkyl group.

[0164] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form a monocyclic carbon atom. 6-8 It forms a heterocycloalkyl group.

[0165] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form a bicyclic carbon atom. 6-8 It forms a heterocycloalkyl group.

[0166] In this embodiment, R 1 and R 2 These, together with the nitrogen atom to which they are bonded, form a condensation C 4~8 It forms a heterocycloalkyl group.

[0167] In this embodiment, R 1 and R 2 These, together with the nitrogen atom to which they are bonded, form an unsubstituted C 4~8 It forms a heterocycloalkyl group.

[0168] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form unsubstituted and monocyclic or fused bicyclic carbon atoms. 4~8 It forms a heterocycloalkyl group.

[0169] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form unsubstituted and monocyclic C 4~8 It forms a heterocycloalkyl group.

[0170] In this embodiment, R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form unsubstituted and fused bicyclic C 4~8 It forms a heterocycloalkyl group.

[0171] In this embodiment, R 1 These are, independently, hydrogen, and optionally substituted C. 1~6 Alkyl, optionally substituted C 1~6 Haloalkyl, optionally substituted C 3~8Cycloalkyl, optionally substituted C 4~14 Alkylenecycloalkyl, optionally substituted C3-C8 heterocycloalkyl, optionally substituted C4-C 14 Alkylene heterocycloalkyl, optionally substituted C 6~12 Aryl, optionally substituted C 7~18 Alkylenearyl, optionally substituted C 5~10 Heteroaryl and optionally substituted C 6~16 Selected from alkylene heteroaryls, R 2 This is an independently and arbitrarily substituted C 3~8 Cycloalkyl, optionally substituted C 4~14 Alkylenecycloalkyl, optionally substituted C3-C8 heterocycloalkyl, optionally substituted C4-C 14 Alkylene heterocycloalkyl, optionally substituted C 6~12 Aryl, optionally substituted C 7~18 Alkylenearyl, optionally substituted C 5~10 Heteroaryl and optionally substituted C 6~16 Selected from alkylene heteroaryls, Or, R 1 and R 2 These, together with the atoms to which they are bonded, form O, S, S(O), SO2, N, and NR. 4 Optionally substituted C containing 0, 1, or 2 additional ring heteromologies selected from 3~8 It forms a heterocycloalkyl group.

[0172] In this embodiment, R 2 This is C, which is optionally substituted. 1~6 It is a haloalkyl group.

[0173] In this embodiment, R 1 This is independently selected from hydrogen, methyl, ethyl, isopropyl, and cyclopropyl.

[0174] In this embodiment, R2 The element is selected from hydrogen, trifluoroisopropyl, cyclopropyl, difluorocyclopropyl, cyclobutyl, methylenecyclopropyl, 1-cyclopropyl-ethyl, benzyl, methoxybenzyl, and fluorobenzyl.

[0175] In this embodiment, R 1 and R 2 These, together with the nitrogen they are bound to, result in the following: -NH2, [ka] It forms one of the following.

[0176] In this embodiment, R 1 and R 2 These, together with the nitrogen they are bound to, result in the following: -NH2, [ka] It forms one of the following.

[0177] In some embodiments, R 1 and R 2 These, together with the nitrogen they are bound to, result in the following: [ka] It forms one of the following.

[0178] In this embodiment, R 3 These are, independently, hydrogen and C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 Selected from alkylene cycloalkyl, Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, C 3~12 Forms heterocycloalkyl groups, C3~12 Heterocycloalkyls include halogens, (O), CN, and C. 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 4 , C(O)N(R 4 )2, OR 4 , N(R 4 )2, NO2, SR 4 SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyls, as well as O, S, N, S(O), SO2, and NR 4 C containing one or two ring heteroparts selected from 3~6 It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 4 These are, independently, hydrogen and C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~7 Selected from heterocycloalkyl groups, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl sulfonyl, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Each R 5 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Selected from heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. In this embodiment, R 3 These are independently hydrogen and optionally substituted C 1~6 Selected from alkyl groups, Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which they are bonded, and is optionally substituted with C 3~12 It forms a heterocycloalkyl group.

[0179] In some embodiments, R 3 It is hydrogen.

[0180] In some embodiments, R 3 This is C, which is optionally substituted. 1~6 It is alkyl.

[0181] In some embodiments, R 1 H is R 2 H is R 3 C is optionally substituted. 1~6 It is alkyl. In some embodiments, R 1 H is R 2 H is R 3 C is optionally substituted. 1~4 It is alkyl. In some embodiments, R1 H is R 2 H is R 3 C is optionally substituted. 1~3 It is alkyl.

[0182] In this embodiment, R 3 and R 2 These combine with the atoms to which they are bonded, and are optionally substituted with C 3~12 It forms a heterocycloalkyl. In these embodiments, the compound of formula (I) is of formula (IV). [ka] It may be provided as a compound of the formula, in which, R 1 and R 9 However, as defined in any embodiment or aspect of this specification, G is replaced by C in an arbitrary choice. 3~12 Heterocycloalkyl, preferably C 4~6 It is a heterocycloalkyl group. The heterocycloalkyl group is "C x~y The reference to "" includes the nitrogen atom indicated within the number of atoms. Therefore, or, G may be defined as a 3- to 12-membered heterocycloalkyl group containing the nitrogen atom to be subtracted and, optionally, one or two additional ring heteromolets selected from O, S, S(O), SO2, N, NH, and NCH3, with the remaining ring atoms being carbon atoms.

[0183] R 9 In this embodiment, R 9 These are independently hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. In this embodiment, R 9 These are, independently, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 , OC(O)OR 13 , OCN(R) 13 )2, OS(O)R 13 OS(O)N(R) 13 )2, OSO2R 13 , OP(O)(OR 13 )2, OC 1~6 Alkilen P(O)(OR) 13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryl, C 4~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C2-C6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 1~6 Alkylamine, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents independently selected from the original, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 4~16 Alkylene heteroaryls are (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring heteroparts selected from 3~6 Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R 13 These are, independently, hydrogen and C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Selected from alkylene heteroaryls, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkylene heterocycloalkyl, C 6~12 Ariel, C 7~18 Alkylenearyl, C 5~10 Heteroaryls, and C 6~16 Alkylene heteroaryls are halogens, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenil, C 2~6 Haloalkenil, C 2~6 Alkinyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl and C containing one or two ring heteromolets selected from O, S, S(O), SO2, N, NH and NCH3. 3~6 Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. In this embodiment, R 9 These are, independently, halogen, CN, -OH, C 1~6 Haloalkyl, C 1~6 Alkoxy, and C1~6 Selected from haloalkoxys, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxys are halogens, CN, and C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents that are independently selected from the original molecule.

[0184] In this embodiment, R 9 These are, independently, halogen, -OH, C 1~6 Haloalkyl, C 1~6 Alkoxy, and C 1~6 Selected from haloalkoxys, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxys are halogens, CN, and C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 13 , C(O)N(R 13 )2, OR 13 , N(R 13 )2, NO2, SR 13 , and SO2R 13 It is optionally substituted with one or more substituents that are independently selected from the original molecule.

[0185] In this embodiment, R 9 is Halo, CN, -OH, C 1~4 Alkoxy, C 1~4 Haloalkoxy and C 1~4 Selected from haloalkyl groups.

[0186] In this embodiment, R 9 is halo, -OH, C 1~4Alkoxy, C 1~4 Haloalkoxy and C 1~4 Selected from haloalkyl groups.

[0187] In this embodiment, R 9 The compound is selected from fluoro, chloro, bromo, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0188] In this embodiment, R 9 The compound is selected from fluoro, chloro, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0189] In this embodiment, R 9 It is fluoro.

[0190] In this embodiment, R 9 is fluoro, and R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, do not contain additional ring heteromones. 4~8 It forms a heterocycloalkyl group.

[0191] In this embodiment, R 9 is fluoro, and R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form a monocyclic or condensed C 4~8 It forms a heterocycloalkyl group.

[0192] In this embodiment, R 9 is fluoro, and R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form a monocyclic C 4~8 It forms a heterocycloalkyl group.

[0193] In this embodiment, R 9 is fluoro, and R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, are unsubstituted, monocyclic, or condensed C 4~8It forms a heterocycloalkyl group.

[0194] In this embodiment, R 9 is fluoro, and R 1 and R 2 These, together with the nitrogen atoms to which they are bonded, form unsubstituted and monocyclic C 4~8 It forms a heterocycloalkyl group.

[0195] In this embodiment, R 9 That is Chlorophyll.

[0196] In this embodiment, R 9 It is Bromo.

[0197] In this embodiment, R 9 This is CN.

[0198] In this embodiment, R 9 It is methoxy.

[0199] In this embodiment, R 9 It is trifluoromethoxy.

[0200] R 8 and R 10 In this embodiment, R 8 It is hydrogen.

[0201] In this embodiment, R 10 It is hydrogen.

[0202] In this embodiment, R 8 and R 10 It is hydrogen.

[0203] In this embodiment, R 8 and R 10 is hydrogen, and R 9 It is not hydrogen.

[0204] In this embodiment, R 8 and R 10 is hydrogen, and R 9The compound is selected from fluoro, chloro, bromo, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0205] In this embodiment, R 8 and R 10 is hydrogen, and R 9 It is fluoro.

[0206] Further formula of this compound In embodiments, the compound of formula (I) is selected from S1 to S75, or its pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs.

[0207] In embodiments, the compound of formula (I) is selected from S1 to S42, or its pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs.

[0208] In the embodiment, the compound of formula (I) is selected from S1 to S28 and S30 to S75, or their pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs.

[0209] In embodiments, the compound of formula (I) is selected from S1, S2, S5, S6, S7, S8, S9, S11, S12, S15, S16, S17, S25, S30-S34, S41-S75, or their pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs.

[0210] Form of compounds In the case of solid compounds, the compounds, agents, and salts of the present invention may exist in different crystalline or polymorphic forms, and it will be understood by those skilled in the art that all of these are intended to be within the scope of the present invention and the specified formulas.

[0211] This invention encompasses all crystalline forms of the compound of formula (I), including anhydrous crystalline form, hydrate, solvate, and mixed solvate. If any of these crystalline forms exhibit polymorphism, all polymorphs are within the scope of this invention.

[0212] Formula (I) is intended to encompass the solvated and non-solvated forms of a compound, where applicable. Therefore, formula (I) includes compounds having the shown structure, including hydrated or solvated forms, as well as non-hydrated and non-solvated forms.

[0213] Compounds of formula (I), or their salts, tautomers, N-oxides, polymorphs, or prodrugs may be provided in the form of solvates. Solvates contain either stoichiometric or nonstoichiometric amounts of solvent and may be formed during a crystallization process using water, alcohols such as methanol, ethanol, or isopropyl alcohol, or pharmaceutically acceptable solvents such as DMSO, acetonitrile, dimethylformamide (DMF), or acetic acid. The solvates form part of the crystal lattice either by non-covalent bonding or by occupying holes in the crystal lattice. Hydrates are formed when the solvent is water, and alkoxides are formed when the solvent is alcohol. It would be convenient for the solvates of the compounds of the present invention to be prepared or formed during the processes described herein. Generally, the solvated form is considered equivalent to the non-solvated form for the purposes of the present invention.

[0214] Basic nitrogen-containing groups include C12, methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides. 1~6 Alkyl halides; they can be quaternized with agents such as dimethyl and dialkyl sulfates like diethyl sulfate.

[0215] Nitrogen-containing groups can also be oxidized to form N-oxides.

[0216] Compounds of formula (I) that form crystalline solids, or their salts, tautomers, N-oxides, solvates, and / or prodrugs, may exhibit polymorphism. All polymorphic forms of compounds, salts, tautomers, N-oxides, solvates, and / or prodrugs are within the scope of the present invention.

[0217] Compounds of formula (I) may exhibit tautomerism. Tautomers are typically two interchangeable forms of a molecule that exist in equilibrium. Any tautomer of a compound of formula (I) should be understood to be within the scope of the present invention.

[0218] The compound of formula (I) may contain one or more stereocenters. All stereoisomers of the compound of formula (I) are within the scope of the present invention. Examples of stereoisomers include enantiomers, diastereomers, geometric isomers (E and Z olefin forms, and cis and trans substitution patterns), and atropisomers. In some embodiments, the compound is a stereoisomerically concentrated form of the compound of formula (I) at any stereocenter. The compound may be concentrated in one stereoisomer by at least about 60, 70, 80, 90, 95, 98, or 99% compared to another stereoisomer.

[0219] Compounds of formula (I), or their salts, tautomers, solvates, N-oxides, and / or stereoisomers, may be isotopically enriched with one or more isotopes of the atoms present in the compound. For example, the compound may be enriched with one or more of the following minor isotopes: 2 H, 3 H, 13 C, 14 C, 15 N, 17 O and / or 18 F, preferably 2 H. isotopes can be considered enriched if their abundance is greater than their natural abundance.

[0220] A “prodrug” is a compound that may not fully meet the structural requirements of the compounds provided herein, but which, after administration to a subject or patient, is modified in vivo to produce a compound of formula (I) provided herein. For example, a prodrug may be an acylated derivative of a compound provided herein. Prodrugs include compounds in which a hydroxy, carboxy, amine, or sulfhydryl group is bonded to any group that, upon administration to a mammalian subject, cleaves to form a free hydroxy, carboxy, amino, or sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, phosphate, and benzoate derivatives of alcohol and amine functional groups in the compounds provided herein. Prodrugs of the compounds provided herein may be prepared by modifying functional groups present in the compound in such a manner that the modification cleaves in vivo to produce the parent compound.

[0221] Prodrugs include compounds in which an amino acid residue, or a polypeptide chain of two or more (e.g., two, three, or four) amino acid residues, is covalently bonded to a free amino acid and an amide group of the compound of formula (I). The amino acid residues include 20 naturally occurring amino acids commonly designated by three letter symbols, and also include 4-hydroxyproline, hydroxylysine, desmosine, isodesmosine, 3-methylhistidine, norvaline, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine, and methionine sulfone. Prodrugs also include compounds in which a carbonate, carbamate, amide, and alkyl ester is covalently bonded to the substituent of formula (I) via a carbonyl carbon prodrug side chain.

[0222] Composition, formulation, and administration mode The compound of formula (I) may be administered alone or in the form of a pharmaceutical composition. In practice, the compound of formula (I) is usually administered in the form of a pharmaceutical composition, i.e., in combination with at least one pharmaceutically acceptable excipient. The proportion and nature of any pharmaceutically acceptable excipient is determined by the properties of the selected compound of the invention, the selected route of administration, and standard pharmaceutical practice.

[0223] In another embodiment, a pharmaceutical composition is provided comprising a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, solvate, metabolite, or polymorph thereof, and at least one pharmaceutically acceptable excipient.

[0224] The pharmaceutical compositions of this disclosure typically comprise a therapeutically effective amount of one or more active ingredients mixed with one or more pharmaceutically and physiologically acceptable formulation materials. Suitable formulation materials include, but are not limited to, antioxidants, preservatives, colorants, flavorings and diluents, emulsifiers, suspensions, solvents, fillers, bulking agents, buffers, delivery vehicles, diluents, excipients, and / or pharmaceutical adjuvants. For example, a suitable vehicle may be water for injection, physiological saline solution, or artificial periliform, optionally supplemented with other materials common to compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles.

[0225] The pharmaceutical compositions of this disclosure further include pharmaceutically acceptable carriers, which contain any solvent, diluent, or other liquid vehicle, dispersion or suspension aids, surfactants, isotonic agents, thickeners or emulsifiers, preservatives, solid binders, lubricants, etc., suitable for a desired specific dosage form, as used herein. Remington's Pharmaceutical Sciences, Sixteenth Edition, EW Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in the formulation of pharmaceutical compositions and known techniques for their preparation. Unless any conventional carrier medium is incompatible with the compounds of the present invention, for example, by producing any undesirable biological effect or otherwise interacting in a detrimental manner with other components of the pharmaceutical composition, its use is assumed to be within the scope of this disclosure. Some examples of materials that can function as pharmaceutically acceptable carriers include sugars, e.g., lactose, glucose, and sucrose; starches, e.g., corn starch and potato starch; cellulose and its derivatives, e.g., sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, e.g., cocoa butter and suppository waxes; oils, e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols, e.g., propylene glycol Lentil glycol; esters, e.g., ethyl oleate and ethyl laurate; agar; buffers, e.g., magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol and phosphate buffer, as well as other non-toxic, suitable lubricants, e.g., sodium lauryl sulfate and magnesium stearate, and colorants, release agents, coating agents, sweeteners, flavoring agents and fragrances. Preservatives and antioxidants may also be present in the composition at the discretion of the compounder.

[0226] Various dosing units are preferably provided as separate dosing tablets, capsules, lozenges, sugar-coated tablets, gums, or other types of solid formulations. Capsules may encapsulate powders, liquids, or gels. Solid formulations may be swallowed or may be of a suctionable or chewable type (either brittle or gum-like). The present invention envisions dosing unit holding devices other than blister packs, such as packages including bottles, tubes, canisters, and packets. Dosing units may further include conventional excipients well known in pharmaceutical formulation practice, such as binders, gelling agents, fillers, tableting lubricants, disintegrants, surfactants, and colorants, as well as suctionable or chewable formulations.

[0227] The compound of formula (I) may be administered in any form and via any route that makes the compound biologically available.

[0228] The compositions described herein may be administered systemically or directly to the site of the disease or condition.

[0229] The compositions described herein may be formulated from compounds according to formula (I) for any suitable route of administration, including, for example, oral, rectal, nasal, vaginal, topical (including percutaneous, transchucral, transocular, and sublingual), parenteral (subcutaneous, intraperitoneal, intradermal, intravascular (e.g., intravenous), intramuscular, spinal, intracranial, intrathecal, intraocular, periorbital, intraorbital, synovial, and intraperitoneal injection, intracisional injection, and other similar injection or infusion techniques), inhalation, insufflation, infusion, or implantation techniques (e.g., as a sterile, injectable aqueous or nonaqueous solution or suspension). In some embodiments, the compositions described herein may be administered by oral, nasal, intravenous, intramuscular, topical, subcutaneous, rectal, vaginal, or urethral application.

[0230] Compositions intended for oral use may further contain one or more components, such as sweeteners, flavorings, colorings, and / or preservatives, to provide an attractive and palatable preparation. Tablets contain the active ingredient in mixture with physiologically acceptable excipients suitable for tablet production. Such excipients include, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulators and disintegrants such as corn starch or alginic acid; binders such as starch, gelatin, or acacia; and lubricants such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated or coated by known techniques to slow disintegration and absorption in the gastrointestinal tract, thereby providing a sustained effect over a longer period. For example, time-delaying materials such as glyceryl monostearate or glyceryl distearate may be used.

[0231] Formulations for oral use may be presented as rigid gelatin capsules in which the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin, or as soft gelatin capsules in which the active ingredient is mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil.

[0232] Oily suspensions can be formulated by suspending the active ingredient in a vegetable oil such as arachis oil, olive oil, sesame oil, or coconut oil, or in a mineral oil such as liquid paraffin. Oily suspensions may contain thickeners such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners and / or flavoring agents, such as those described above, may be added to provide an oral preparation with a pleasant mouthfeel. Such suspensions can be preserved by adding antioxidants such as ascorbic acid.

[0233] Dispersible powders and granules suitable for preparing aqueous suspensions by the addition of water provide the active ingredient in mixture with a dispersant or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersants or wetting agents and suspending agents are exemplified by those already mentioned. Additional excipients such as sweeteners, flavoring agents, and coloring agents may also be present.

[0234] The pharmaceutical composition may also be in the form of an oil-in-water emulsion. The oil phase may be a vegetable oil such as olive oil or arachis oil, a mineral oil such as liquid paraffin, or a mixture thereof. Suitable emulsifiers include naturally occurring gums such as acacia gum or tragacanth gum, naturally occurring phosphatides such as soy lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrous substances such as sorbitan monooleate, and condensation products of partial esters derived from fatty acids and hexitol with ethylene oxides such as polyoxyethylene sorbitan monooleate. The emulsion may also contain one or more sweeteners and / or flavoring agents.

[0235] Syrups and elixirs may be formulated with sweeteners such as glycerol, propylene glycol, sorbitol, or sucrose. Such formulations may also contain one or more analgesics, preservatives, flavorings, and / or colorings.

[0236] The composition may further contain one or more components adapted to improve the stability or efficacy of the formulation to be applied, such as stabilizers, suspending agents, emulsifiers, viscosity modifiers, gelling agents, preservatives, antioxidants, skin penetration enhancers, humectants, and sustained-release materials. Examples of such components are described in Martindale - The Extra Pharmacopoeia (Pharmaceutical Press, London 1993) and Martin (ed.), Remington's Pharmaceutical Sciences. The formulation may contain microcapsules such as hydroxymethylcellulose or gelatin microcapsules, liposomes, albumin microparticles, microemulsions, nanoparticles, or nanocapsules.

[0237] Suitable preservatives include, but are not limited to, antimicrobial agents such as methylparaben, propylparaben, sorbic acid, benzoic acid, and formaldehyde, as well as physical stabilizers and antioxidants such as vitamin E, sodium ascorbate / ascorbic acid, and propyl gallate. Suitable humectants include, but are not limited to, lactic acid and other hydroxy acids and their salts, glycerin, propylene glycol, and butylene glycol. Suitable emollients include lanolin alcohol, lanolin, lanolin derivatives, cholesterol, petrolatum, isostearyl neopentanoate, and mineral oil. Suitable fragrances and colors include, but are not limited to, FD&C Red No. 40 and FD&C Yellow No. 5. Other suitable additional ingredients that may be included in topical formulations include, but are not limited to, abrasives, absorbents, anticoagulants, defoamers, antistatics, astringents (such as witch hazel), alcohols and herbal extracts, such as chamomile extract, binders / excipients, buffers, chelating agents, film-forming agents, conditioning agents, propellants, opacifiers, pH adjusters, and protective agents.

[0238] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid dosage form may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers, and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (specifically, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, as well as mixtures thereof. In addition to inert diluents, the oral composition may also contain adjuvants, such as wetting agents, emulsifiers, and suspending agents, sweeteners, flavoring agents, and fragrance agents.

[0239] Injectable preparations, such as sterile injectable aqueous or oily suspensions, can be formulated by known techniques using suitable dispersants or wetting agents and suspending agents. Sterile injectable preparations may also be sterile injectable solutions, suspensions, or emulsions in non-toxic, parenterally acceptable diluents or solvents, such as a solution in 1,3-butanediol. Acceptable vehicles and solvents that can be used include water, Ringer's solution, USP, and isotonic sodium chloride solution. In addition, sterile fixatives have conventionally been used as solvents or suspension media. For this purpose, any non-irritating fixative, including synthetic mono or diglycerides, can be used. In addition, fatty acids such as oleic acid are used in the preparation of injectable preparations.

[0240] Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating a bactericide in the form of a sterile solid composition that can be dissolved or dispersed in sterile water or other sterile injectable medium before use.

[0241] Pharmaceutical compositions may be formulated as inhalation formulations including sprays, mists, or aerosols. In the case of inhalation formulations, the compositions or combinations provided herein may be delivered via any inhalation method known to those skilled in the art. Such inhalation methods and devices include, but are not limited to, metered-dose inhalers having propellants such as CFCs or HFAs or physiologically and environmentally acceptable propellants. Other suitable devices include respiratory inhalers, multi-dose dry powder inhalers, and aerosol nebulizers. Aerosol formulations for use in the method of the subject may typically contain a propellant, a surfactant, and a co-solvent and be filled into a conventional aerosol container closed by a suitable metering valve.

[0242] Inhalation compositions may include liquid or powder compositions containing active ingredients suitable for spray and intrabronchial use, or aerosol compositions administered via an aerosol unit dispensing a fixed dose. Suitable liquid compositions contain the active ingredient in an aqueous, pharmaceutically acceptable inhalation solvent such as isotonic saline or bacteriostatic water. The solution is administered by a pump or push-actuated spray dispenser, or by other conventional means to bring about or enable the inhalation of the required dose of the liquid composition into the patient's lungs. For example, suitable formulations with a liquid carrier for administration as a nasal spray or nasal drops contain an aqueous or oily solution of the active ingredient.

[0243] Compositions suitable for rectal administration are preferably presented as unit-dose suppositories. These can be prepared by at least partially dispersing the active ingredient in one or more lipophilic bases, and then forming a mixture.

[0244] Pharmaceutical compositions can be formulated as sustained-release formulations, such as capsules, that create sustained release of the active substance after administration. Such formulations can generally be prepared using well-known techniques and may be administered, for example, orally, rectally, or subcutaneously, or by implantation at a desired target site. The carrier for use in such formulations may be biocompatible and biodegradable. Preferably, the formulation provides a relatively constant level of active substance release. The amount of active substance contained in the sustained-release formulation depends, for example, on the implantation site, the rate and expected duration of release, and the nature of the condition to be treated.

[0245] Those skilled in the art can easily select an appropriate dosage form and route of administration depending on the specific characteristics of the selected compound, the disease or condition to be treated, the stage of the disease or condition, and other relevant circumstances.

[0246] It will be understood that the specific dose level for any particular patient will depend on a variety of factors, including the activity of the particular compound used, age, weight, general health status, sex, diet, administration time, route of administration, number of doses, and excretion rate, concomitant drug use (i.e., other drugs used to treat the patient), and the severity of the particular disorder being treated.

[0247] The term "therapeutic dose" generally refers to the amount of one or more active ingredients of the present invention that (i) treat a particular disease, condition, or disorder; (ii) reduce, improve, or eliminate one or more signs or symptoms of a particular disease, condition, or disorder; or (iii) delay the onset of one or more signs or symptoms of a particular disease, condition, or disorder as described herein.

[0248] Typically, therapeutically effective dosages are formulated to include concentrations (by weight) of at least about 0.1% to a maximum of about 50% or more, and all combinations and partial combinations within that range. Compositions may be formulated to contain one or more of the active ingredients described herein at concentrations of about 0.1% to less than about 50%, for example, about 49, 48, 47, 46, 45, 44, 43, 42, 41 or 40%, and concentrations greater than about 0.1%, for example, about 0.2, 0.3, 0.4 or 0.5% to less than about 40%, for example, about 39, 38, 37, 36, 35, 34, 33, 32, 31 or 30%. Exemplary compositions may contain concentrations of about 0.5% to less than about 30%, for example, about 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20%, with concentrations greater than about 0.5%, for example, about 0.6, 0.7, 0.8, 0.9, or 1% to less than about 20%, for example, about 19, 18, 17, 16, 15, 14, 13, 12, 11, or 10%. Compositions may contain concentrations greater than about 1%, for example, about 2% to less than about 10%, for example, about 9 or 8%, which includes concentrations greater than about 2%, for example, about 3 or 4% to less than about 8%, for example, about 7 or 6%. The activator may be present at a concentration of, for example, about 5%. In all cases, the amount may be adjusted to compensate for any differences in the amount of active ingredient actually delivered to the treated cells or tissues.

[0249] The frequency of administration may be once daily, two, three, or four times daily. The duration of treatment may be for the duration of the detectable disease.

[0250] In some embodiments, the pharmaceutical composition comprises a compound described in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, an additional therapeutic agent, and a pharmaceutically acceptable excipient.

[0251] Additional agents may be any suitable agents described herein. In some embodiments, the additional agents are psychoactive agents, including those described herein. In some embodiments, the additional agents are useful for treating diseases, disorders, or conditions by activation of serotonin receptors, including those described herein. In some embodiments, the additional agents are selected from any one of the following, including those described herein: agents for psychosis and / or neuropsychopathy; agents for mental disorders and / or psychotic symptoms; agents for attention deficit hyperactivity disorder and / or attention deficit disorder; agents for dementia and / or Alzheimer's disease; and agents for addiction disorders.

[0252] Purpose This disclosure provides methods for using the compounds and compositions of formula (I) described in any one of the preceding paragraphs. This disclosure also provides methods for delivering the compounds or compositions of formula (I) of this disclosure (e.g., effective amounts of the compounds or compositions) to a target that requires such delivery.

[0253] In another aspect, the Disclosure provides a method for treating a disease in a person in need of treatment for the disease, comprising administering to the person in need an effective amount (e.g., a therapeutically effective amount) of a compound or composition (e.g., a pharmaceutical composition) of the Disclosure.

[0254] In another aspect, the Disclosure provides a method for preventing a disease in a subject in need of disease prevention, comprising administering to the subject in need an effective amount (e.g., a therapeutically effective amount) of a compound or composition of formula (I) of the Disclosure (e.g., a pharmaceutical composition).

[0255] In other embodiments of this specification, the use of compounds or compositions of formula (I) of this disclosure in the manufacture of pharmaceuticals for use in the methods of this disclosure (for example, methods for delivering an activator to an object that needs to be delivered an activator, methods for treating a disease in an object that needs to be treated, and methods for preventing a disease in an object that needs to be prevented).

[0256] In other embodiments of this specification, the use of compounds or compositions of formula (I) of this disclosure in the methods of this disclosure (for example, methods for delivering an activator to an object that needs to be delivered an activator, methods for treating a disease in an object that needs to be treated a disease, and methods for preventing a disease in an object that needs to be prevented a disease) is provided.

[0257] In certain embodiments, the effective dose is effective in treating a disease. In certain embodiments, the effective dose is effective in preventing a disease.

[0258] In another aspect, the present disclosure provides a method for treating a disease, disorder, or condition by activation of serotonin receptors, the method comprising administering a compound of formula (I) or a pharmaceutical composition described herein to a subject in need thereof.

[0259] In another aspect, the Disclosure provides a method for preventing a disease, disorder, or pathological condition by activation of serotonin receptors, the method comprising administering a compound or pharmaceutical composition of formula (I) described herein to a subject in need thereof.

[0260] In another embodiment, the present disclosure provides a method for treating a disease, disorder, or condition by activation of serotonin receptors, the method comprising administering to a subject requiring such treatment a compound or pharmaceutical composition of formula (I) described herein in combination with another known agent useful for treating a disease, disorder, or condition by activation of serotonin receptors. Other known agents useful for treating a disease, disorder, or condition by activation of serotonin receptors may be any suitable agents known in the art, including those described herein.

[0261] In another embodiment, the present disclosure provides a method for preventing a disease, disorder, or condition by activation of serotonin receptors, the method comprising administering to a subject in need thereof a compound or pharmaceutical composition of formula (I) described herein in combination with another known agent useful for preventing a disease, disorder, or condition by activation of serotonin receptors.

[0262] In a particular embodiment, the serotonin receptor is 5-HT 2A That is the case.

[0263] In a particular embodiment, the serotonin receptor is 5-HT 2A and 5-HT 2C It is one or both of the above. In addition or alternatively, in some embodiments, the serotonin receptor is 5-HT 2B isn't it.

[0264] In some embodiments, the compound of formula (I) in this disclosure is 5-HT 2C Receptors and 5-HT 2B Preferably 5-HT receptor, rather than one or both of the receptors. 2B Rather than receptors, 5-HT 2A It is selective for the receptor. In some embodiments, the compound of formula (I) is 5-HT 2A Receptors and 5-HT 2B Preferably 5-HT receptor, rather than one or both of the receptors. 2B Rather than receptors, 5-HT 2CIt is selective for the receptor. In some embodiments, the compound of formula (I) is 5-HT 2B 5-HT receptor 2A Receptors and 5-HT 2C It is selective for receptors.

[0265] In some embodiments, the compound of formula (I) of the present disclosure is determined by assays of calcium flux activity, such as measuring changes in intracellular calcium, to be less than about 1 mM, less than about 100 μM, less than about 10 μM, less than about 1 μM, or less than about 100 nM, or less than about 10 nM of 5-HT 2A EC about receptors 50 The values ​​are as follows: In some embodiments, the compound of formula (I) is determined by an assay of calcium flux activity or IP1 accumulation to be less than about 1 mM, less than about 900 μM, less than about 800 μM, less than about 700 μM, less than about 600 μM, less than about 500 μM, less than about 400 μM, less than about 300 μM, less than about 200 μM, less than about 100 μM, less than about 90 μM, less than about 80 μM, less than about 70 μM, less than about 60 μM, less than about 50 μM, less than about 40 μM, and about 30 5-HT in any equivalent unit of measurement (e.g., mol / L), less than μM, less than approximately 20 μM, less than approximately 10 μM, less than approximately 9 μM, less than approximately 8 μM, less than approximately 7 μM, less than approximately 6 μM, less than approximately 5 μM, less than approximately 4 μM, less than approximately 3 μM, less than approximately 2 μM, less than approximately 1 μM, less than approximately 900 nM, less than approximately 800 nM, less than approximately 700 nM, less than approximately 600 nM, less than approximately 500 nM, less than approximately 400 nM, less than approximately 300 nM, less than approximately 200 nM, or less than approximately 100 nM, or any equivalent unit of measurement (e.g., mol / L). 2A EC about receptors 50 It exhibits the following characteristics.

[0266] In some embodiments, the compound of formula (I) of the present disclosure is determined by assays of calcium flux activity, such as measuring changes in intracellular calcium, to be less than about 1 mM, less than about 100 μM, less than about 10 μM, less than about 1 μM, or less than about 100 nM, or less than about 10 nM of 5-HT 2C EC about receptors 50The values ​​are as follows: In some embodiments, the compound of formula (I) is determined by a calcium flux activity assay to be less than approximately 1 mM, less than approximately 900 μM, less than approximately 800 μM, less than approximately 700 μM, less than approximately 600 μM, less than approximately 500 μM, less than approximately 400 μM, less than approximately 300 μM, less than approximately 200 μM, less than approximately 100 μM, less than approximately 90 μM, less than approximately 80 μM, less than approximately 70 μM, less than approximately 60 μM, less than approximately 50 μM, less than approximately 40 μM, less than approximately 30 μM. 5-HT in any equivalent unit of measurement (e.g., mol / L), less than approximately 20 μM, less than approximately 10 μM, less than approximately 9 μM, less than approximately 8 μM, less than approximately 7 μM, less than approximately 6 μM, less than approximately 5 μM, less than approximately 4 μM, less than approximately 3 μM, less than approximately 2 μM, less than approximately 1 μM, less than approximately 900 nM, less than approximately 800 nM, less than approximately 700 nM, less than approximately 600 nM, less than approximately 500 nM, less than approximately 400 nM, less than approximately 300 nM, less than approximately 200 nM, or less than approximately 100 nM, or any equivalent unit of measurement (e.g., mol / L). 2C EC about receptors 50 It exhibits the following characteristics.

[0267] In some embodiments, the compound of formula (I) of the present disclosure is determined by assays described herein, such as assays of calcium flux activity including measuring changes in intracellular calcium, to be present in concentrations greater than about 1 μM, greater than about 10 μM, or greater than about 100 μM of 5-HT 2B EC about receptors 50 It exhibits a value.

[0268] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is psychosis or neuropsychiatric disorder. Accordingly, this application also includes a method for treating psychosis or neuropsychiatric disorder, comprising administering a compound or composition of formula (I) described herein to a subject in need thereof. This application also includes the use of the compounds of formula (I) of this disclosure for the treatment of psychosis or neuropsychiatric disorder, and the use of the compounds of formula (I) of this disclosure for the preparation of pharmaceuticals for the treatment of psychosis or neuropsychiatric disorder. This application further includes the compounds of formula (I) of this disclosure for use in the treatment of psychosis or neuropsychiatric disorder.

[0269] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is psychosis or neuropsychiatric, and the compounds of formula (I) of this disclosure are administered in combination with one or more additional agents for psychosis or neuropsychiatric. The one or more additional agents for psychosis or neuropsychiatric may be any suitable agents known in the art, including those described herein. In some embodiments, additional agents for psychosis or neuropsychiatric conditions are selected from antipsychotics, including typical and atypical antipsychotics; antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) (e.g., bupropion); anxiolytics, including benzodiazepines such as alprazolam; agents for addiction disorders such as alcohol dependence (e.g., disulfiram), nicotine dependence (e.g., varenicline) and opioid use disorder (e.g., methadone, buprenorphine, buprenorphine-naloxone, and buprenorphine long-acting injection); mood stabilizers, e.g., lithium; and antispasmodics, e.g., carbamazepine, divalproex (valproic acid), lamotrigine, gabapentin, and topiramate.

[0270] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is neurodegeneration. Accordingly, this application also includes a method for treating neurodegeneration, comprising administering a compound or composition of formula (I) described herein to a subject in need thereof. This application also includes the use of the compounds of formula (I) of this disclosure for treating neurodegeneration, and the use of the compounds of formula (I) of this disclosure for the preparation of pharmaceuticals for treating neurodegeneration. This application further includes the compounds of formula (I) of this disclosure for use in the treatment of neurodegeneration. In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is brain-derived neurotrophic factor (BDNF), mammalian targets of rapamycin (mTOR) activation, and / or reduction of inflammation.

[0271] In some embodiments, the diseases, disorders, or conditions treated by serotonin receptor activation include cognitive impairment; ischemia including stroke; neurodegeneration; intractable substance use disorders; sleep disorders; pain, such as social pain, acute pain, cancer pain, chronic pain, breakthrough pain, bone pain, soft tissue pain, neuralgia, referred pain, hallucinatory pain, neuropathic pain, cluster headaches and migraines; obesity and eating disorders; epilepsy and seizure disorders; neuronal cell death; excitotoxic cell death; or combinations thereof.

[0272] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a mental disorder or psychotic symptom. Accordingly, this application also includes a method for treating a mental disorder or psychotic symptom, comprising administering a compound or composition of formula (I) described herein to a subject in need thereof. This application also includes the use of the compounds of formula (I) of this disclosure for treating mental disorders or psychotic symptoms, and the use of the compounds of formula (I) of this disclosure for the preparation of pharmaceuticals for treating mental disorders or psychotic symptoms. This application further includes the compounds of formula (I) of this disclosure for use in the treatment of mental disorders or psychotic symptoms.

[0273] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a mental disorder or psychotic symptom, and the compounds of formula (I) of this disclosure are administered in combination with one or more additional agents for the mental disorder or psychotic symptom. The one or more additional agents for the mental disorder or psychotic symptom may be any suitable agents known in the art, including those described herein. In some embodiments, the additional agents for the mental disorder or psychotic symptom are selected from typical antipsychotics and atypical antipsychotics. Typical antipsychotic drugs include acepromazine, acetophenazine, bemperidol, bromperidol, butaperazine, carfenadine, chlorproetazine, chlorpromazine, chlorprothixen, clopentixol, siamemazine, dixylazine, droperidol, fluanisone, flupentixol, fluphenazine, fluspirylene, haloperidol, levomepromazine, lenperone, roxapine, mesolidazine, metitepine, morindone, moperone, and oxy Pertine, oxyprotepine, penfluridol, perazine, periciazine, perphenazine, pimozide, pipemperone, piperacetazine, pipothiazine, prochlorperazine, promazine, protipendyl, spiperone, sulforidazine, thiopropazate, thioproperazine, thioridazine, thiothixene, thymiperone, trifluoperazine, trifluperidol, triflupromazine, and zuclopentixol, as well as combinations thereof, may be selected. Atypical antipsychotics may be selected from amoxapine, amisulpride, aripiprazole, asenapine, blonanserin, brexpiprazole, caliprazine, carpipramine, clocapramine, chlorotepine, clotiapine, clozapine, iloperidone, levosulpiride, lurasidone, merperone, mosapramine, nemonapride, olanzapine, paliperidone, perospirone, quetiapine, remoxiprid, reserpine, risperidone, certindol, sulpiride, sultopride, tiapride, veraliprid, ziprasidone, and zotepine, as well as combinations thereof.

[0274] In some embodiments, administering a therapeutically effective amount of the compound of formula (I) of this disclosure to a subject in need does not result in exacerbation of mental disorders or psychotic symptoms, including but not limited to hallucinations and delusions. In some embodiments, administering a therapeutically effective amount of the compound of formula (I) to a subject in need results in improvement of mental disorders or psychotic symptoms, including but not limited to hallucinations and delusions. In some embodiments, administering a therapeutically effective amount of the compound of formula (I) to a subject in need results in improvement of mental disorders or psychotic symptoms.

[0275] In some embodiments, the diseases, disorders, or conditions treated by activation of serotonin receptors are central nervous system (CNS) diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions. Accordingly, this application also includes methods for treating CNS diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions, comprising administering a therapeutically effective amount of a compound or composition of formula (I) of the Disclosure to a subject in need thereof. This application also includes the use of a compound of formula (I) of the Disclosure for the treatment of CNS diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions, and the use of a compound of formula (I) of the Disclosure for the preparation of pharmaceuticals for the treatment of CNS diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions. This application further includes a compound of formula (I) of the Disclosure for use in the treatment of CNS diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions.

[0276] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a central nervous system (CNS) disease, disorder, or condition and / or a nervous system disease, disorder, or condition, and the compounds of formula (I) of the Disclosure are administered in combination with one or more additional agents for central nervous system (CNS) diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions. The one or more additional agents for central nervous system (CNS) diseases, disorders, or conditions and / or nervous system diseases, disorders, or conditions may be any suitable agents known in the art, including those described herein. In some embodiments, additional agents for diseases, disorders, or conditions of the central nervous system (CNS) and / or diseases, disorders, or conditions of the nervous system are selected from lithium, olanzapine, quetiapine, risperidone, ariprazole, ziprasidone, clozapine, divalproex sodium, lamotrigine, valproic acid, carbamazepine, topiramate, levomilunacipran, duloxetine, venlafaxine, citalopram, fluvoxamine, escitalopram, fluoxetine, paroxetine, sertraline, clomipramine, amitriptyline, desipramine, imipramine, nortriptyline, phenelzine, tranylcypromine, diazepam, alprazolam, clonazepam, or any combination thereof. Non-limiting examples of standard care therapies for depression include sertraline, fluoxetine, escitalopram, venlafaxine, or aripiprazole. Non-limiting examples of standard care therapies for depression include citralopram, escitalopram, fluoxetine, paroxetine, diazepam, or sertraline.

[0277] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is selected from attention deficit hyperactivity disorder and attention deficit disorder, and combinations thereof. Accordingly, the application also includes a method for treating attention deficit hyperactivity disorder and / or attention deficit disorder, comprising administering a compound or composition of formula (I) described herein to a subject in need thereof. The application also includes the use of the compounds of formula (I) of the present disclosure for treating attention deficit hyperactivity disorder and / or attention deficit disorder, and the use of the compounds of formula (I) of the present disclosure for the preparation of pharmaceuticals for treating attention deficit hyperactivity disorder and / or attention deficit disorder. The application further includes the compounds of formula (I) of the present disclosure for use in the treatment of attention deficit hyperactivity disorder and / or attention deficit disorder.

[0278] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is attention-deficit hyperactivity disorder and / or attention-deficit disorder, and combinations thereof, and the compounds of formula (I) of the present disclosure are administered in combination with one or more additional agents for attention-deficit hyperactivity disorder and / or attention-deficit disorder, and combinations thereof. One or more additional agents for attention-deficit hyperactivity disorder and / or attention-deficit disorder may be any suitable agents known in the art, including those described herein. In some embodiments, the additional agents for attention-deficit hyperactivity disorder and / or attention-deficit disorder, and combinations thereof are selected from methylphenidate, dexamfetamine, lisdexamfetine, atomoxetine, and amphetamine, and combinations thereof.

[0279] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is selected from dementia and Alzheimer's disease, and combinations thereof. Accordingly, this application also includes a method for treating dementia and / or Alzheimer's disease, comprising administering a compound or composition of formula (I) described herein to a subject in need thereof. This application also includes the use of the compounds of formula (I) of this disclosure for the treatment of dementia and / or Alzheimer's disease, and the use of the compounds of formula (I) of this disclosure for the preparation of pharmaceuticals for the treatment of dementia and / or Alzheimer's disease. This application further includes the compounds of formula (I) of this disclosure for use in the treatment of dementia and / or Alzheimer's disease.

[0280] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is dementia or Alzheimer's disease, and the compounds of formula (I) of the Disclosure are administered in combination with one or more additional agents for dementia or Alzheimer's disease. One or more additional agents for dementia or Alzheimer's disease may be any suitable agents known in the art, including those described herein. In some embodiments, the additional agents for dementia and Alzheimer's disease are selected from acetylcholinesterase inhibitors, NMDA antagonists, and nicotinic agonists. Acetylcholinesterase inhibitors may be selected from donepezil, galantamine, rivastigmine, and fencerin, and combinations thereof. NMDA antagonists may be selected from MK-801, ketamine, phencyclidine, and memantine, and combinations thereof. Nicotinic agonists may be selected from nicotine, nicotinic acid, nicotinic alpha-7 agonists, or alpha-2 beta-4 agonists, or combinations thereof.

[0281] In another aspect, the Disclosure provides a method for treating psychosis, wherein the method comprises administering a compound or pharmaceutical composition of formula (I) described herein to a subject in need thereof. In another aspect, the Disclosure provides a method for preventing psychosis, wherein the method comprises administering a compound or pharmaceutical composition of formula (I) described herein to a subject in need thereof. Psychosis can be a neuropsychiatric condition.

[0282] In certain embodiments, psychosis includes anxiety disorders such as generalized anxiety disorder, panic disorder, social anxiety disorder, and certain phobias; depression such as despair, loss of pleasure, fatigue, and suicidal ideation; mood disorders such as depression, bipolar disorder, cancer-related depression, anxiety, and cyclothymic disorder; psychotic disorders such as hallucinations, delusions, mania, schizophrenia, schizoaffective disorder, and schizotypal disorder; impulse control and addiction disorders such as pyromania, kleptomania, and compulsive gambling; alcoholism; drug addictions such as opioid addiction / dependence, nicotine addiction, cocaine addiction, and marijuana abuse; smoking cessation; and antisocial behavior. Personality disorders such as personality disorders, aggression, obsessive-compulsive personality disorder, and paranoid personality disorder; obsessive-compulsive disorder (OCD), such as thoughts or fears that compel an object to perform a specific customary behavior or routine; post-traumatic stress disorder (PTSD); stress response syndrome (formerly known as adjustment disorder); dissociative disorders and depersonalization disorders, formerly known as multiple personality disorder or "split personality"; factitious disorder; sexual and gender disorders such as sexual dysfunction, gender identity disorder, and paraphilias; and somatic symptom disorders, formerly known as psychosomatic disorders or somatoform disorders.

[0283] In certain embodiments, psychosis is selected from hallucinations and delusions, and combinations thereof. In these embodiments, hallucinations may be selected from visual hallucinations, auditory hallucinations, olfactory hallucinations, gustatory hallucinations, tactile hallucinations, proprioceptive hallucinations, equilibrioceptive hallucinations, nociceptive hallucinations, thermoreceptive hallucinations, and chronoreceptive hallucinations, and combinations thereof.

[0284] In another aspect, the Disclosure provides a method for treating a disease, disorder, or condition of the central nervous system (CNS) and / or a disease, disorder, or condition of the nervous system, the method comprising administering a compound of formula (I) or a pharmaceutical composition described herein to a subject in need thereof.

[0285] In another aspect, the Disclosure provides a method for preventing a disease, disorder, or condition of the central nervous system (CNS) and / or a disease, disorder, or condition of the nervous system, the method comprising administering a compound of formula (I) or a pharmaceutical composition described herein to a subject in need thereof.

[0286] In some embodiments, CNS diseases, disorders, or conditions and / or neurological diseases, disorders, or conditions include neurodevelopmental disorders and neurodegenerative diseases such as Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, Parkinson's disease, and Parkinson's disease-related disorders such as Parkinsonian dementia, corticobasal degeneration, and supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; brittle X syndrome; Angelman syndrome; hereditary motor disorders Ataxia; neuro-otological disorders and oculomotor disorders; neurodegenerative diseases such as retinal amyotrophic lateral sclerosis; tardive dyskinesia; hyperactivity disorder; attention deficit hyperactivity disorder and attention deficit disorder; restless legs syndrome; Tourette syndrome; tic disorder; schizophrenia; autism spectrum disorder; tuberous sclerosis; Rett syndrome; cerebral palsy; reward system disorders including eating disorders such as anorexia nervosa and bulimia nervosa; bulimia nervosa, trichotillomania, dermatopruriticism, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology, as well as combinations thereof, are selected from disorders of the nervous system.

[0287] In another aspect, the Disclosure provides a method for increasing neuronal plasticity, the method comprising contacting a neuron with a compound or pharmaceutical composition of formula (I) described herein in an amount sufficient to increase the neuronal plasticity of the neuron. "Neuroplasticity" refers to the brain's ability to continuously change its structure and / or function throughout the life of an object. Examples of brain changes include, but are not limited to, the ability to adapt to or respond to internal and / or external stimuli due to injury, etc., and the ability to produce new neurites, dendritic spines, and synapses. Increased neuronal plasticity includes, but is not limited to, enhanced nerve growth, enhanced neurite formation, enhanced synapse formation, enhanced dendritic formation, increased dendritic arbor complexity, increased dendritic spine density, and increased excitatory synapses in the brain. In some embodiments, increased neuronal plasticity includes enhanced nerve growth, enhanced neurite formation, enhanced synapse formation, enhanced dendritic formation, increased complexity of dendritic branching, and increased dendritic spine density.

[0288] In some embodiments, neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, psychological disorders, depression, addiction, anxiety, post-traumatic stress disorder, treatment-resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, traumatic brain injury, or substance use disorders can be treated by increasing neuroplasticity.

[0289] In another aspect, the present disclosure provides a method for treating weight, comprising administering an effective amount of the compound of the present invention to a subject in need thereof. Treatment of weight may include the treatment of weight gain; weight loss; metabolic disorders; weight gain associated with pharmacokinetic interventions; weight gain associated with psychosis (including those described herein); eating disorders such as anorexia, bulimia, cachexia; eating behaviors; obesity; diabetes mellitus; insulin resistance; prediabetes; glucose intolerance; hyperlipidemia; and cardiovascular disease.

[0290] In another aspect, the Disclosure provides a method for increasing dendritic spine density, the method comprising contacting a neuron with a compound or pharmaceutical composition of formula (I) described herein in an amount sufficient to increase the dendritic spine density of the neuron.

[0291] In a particular embodiment, the compound of formula (I) produces the maximum number of dendritic crossings, which increases by more than 1.0 times by Scholl analysis.

[0292] In another aspect, the Disclosure provides a method for activating serotonin receptors in cells of either a biological sample or a patient, comprising administering a compound of formula (I) as defined in any one of the embodiments disclosed herein to the cells. The serotonin receptor may be a 5-HT receptor subtype, preferably 5-HT 2A and 5-HT 2C Either one or both of these may be acceptable.

[0293] In some embodiments, the effective dose varies depending on factors such as the disease state of the subject or species, age, sex, and / or weight. In some embodiments, the amount of one or more given compounds corresponding to the effective dose varies depending on factors such as a given drug or compound, pharmaceutical formulation, route of administration, pathological condition, type of disease or disorder, and identity of the subject being treated, but nevertheless, it can be routinely determined by those skilled in the art.

[0294] In some embodiments, the compound of formula (I) of the present disclosure is administered once, two, three, or four times per year. In some embodiments, the compound of the present disclosure is administered at least once per week. However, in other embodiments, the compound is administered to the subject about once every two weeks, three weeks, or one month. In other embodiments, the compound is administered about once per week to about once per day. In other embodiments, the compound is administered one, two, three, four, five, or six times per day. The length of the treatment period depends on various factors such as the severity of the disease, disorder, or condition, the age of the subject, the concentration, and / or the activity of the compound of the present application, and / or combinations thereof. It will also be understood that the effective dosage of the compound used for treatment may increase or decrease over the course of a particular treatment regime. Changes in dosage may be produced and revealed by standard diagnostic assays known in the art. In some cases, chronic administration is required. For example, the compound is administered to the subject in an amount and duration sufficient to treat the subject.

[0295] In some embodiments, the compounds of this application are administered in hallucinogenic or psychotic doses, in combination with psychotherapy or treatment, and may occur once, twice, three times, or four times per year. However, in some embodiments, the compounds are administered to subjects in non-hallucinogenic or non-psychotic doses, once daily, once every two days, once every three days, once a week, once every two weeks, once a month, once every two months, or once every three months.

[0296] The compounds of formula (I) of this disclosure may be used either alone or in combination with other known agents useful for treating diseases, disorders, or conditions by activating serotonin receptors, such as the compounds of this disclosure. When used in combination with other known agents useful for treating diseases, disorders, or conditions by activating serotonin receptors, this is an embodiment in which the compounds of formula (I) are administered simultaneously with those agents. As used herein, “simultaneous administration” of two substances to a subject means providing them so that both substances are simultaneously active in the individual. The exact details of the administration may include administering the two substances within a few hours of each other, or even administering one substance within 24 hours of the other, depending on the pharmacokinetics of the two substances in each other's presence, if the pharmacokinetics are favorable. Designing a suitable administration regimen is commonplace for those skilled in the art. In certain embodiments, the two substances are administered substantially simultaneously, i.e., within a few minutes of each other, or in a single composition containing both substances. Further embodiments of this application involve the administration of a combination of agents to a subject non-simultaneously. In some embodiments, the compounds of formula (I) of this disclosure are administered together with another therapeutic agent, either simultaneously or sequentially in separate unit dosage forms, or together in a single unit dosage form. Accordingly, this application provides a single unit dosage form comprising one or more compounds of formula (I) described herein, an additional therapeutic agent, and a pharmaceutically acceptable carrier.

[0297] In some embodiments, the compounds of this application are used or administered in effective doses, including doses or drug regimens that do not produce clinically meaningful psychedelic / psychotic effects. In some embodiments, the compounds of this application are used in human plasma thyrosine Cmax of 4 ng / mL or less and / or human 5-HT of 40% or less. 2A This is expressed by the human CNS receptor occupancy rate, or by human plasma thyrosine Cmax of 1 ng / mL or less and / or human 5-HT of 30% or less. 2AThe compounds are used or administered in effective doses, including doses or drug regimens that produce a clinical effect similar to that exhibited by human CNS receptor occupancy. In some embodiments, the compounds of this application are used or administered in effective doses, including doses or drug regimens that provide a clinical effect similar to that exhibited by human plasma thyrosine Tmax, with an excess of 60 minutes, 120 minutes, or 180 minutes.

[0298] kit In another embodiment, a kit or manufactured article is provided comprising one or more of the above-described compounds, pharmaceutically acceptable salts, stereoisomers, solvates, metabolites, or polymorphs, and / or pharmaceutical compositions.

[0299] In another embodiment, a kit for use in the therapeutic applications described above, wherein the kit is A container for holding one or more compounds, pharmaceutically acceptable salts, stereoisomers, solvates, metabolites, or polymorphs, and / or pharmaceutical compositions as described herein. A kit is provided that includes a label or accompanying document with instructions for use.

[0300] The present invention, as disclosed and defined herein, will be understood to encompass all alternative combinations of two or more of the individual features mentioned or revealed in the text or drawings. All of these different combinations constitute various alternative embodiments of the present invention. [Examples]

[0301] Scheme 1: Compounds of general formula (I) can be synthesized from appropriately substituted aza-indole according to the outlined sequence of steps in Scheme 1 or similar to those that a person skilled in the art could consider. Similar sequences of synthetic transformations outlined in Scheme 1 have proven to be a viable method for making compounds of general formula (I) available. Friedel-Crafts acylation of aza-indole starting material 7 provides a means of obtaining intermediate 8, which can be subjected to chemoselective silane reduction conditions to provide alkyl chloride intermediate 9. Nucleophilic substitution of alkyl chloride with substituted amines provides compounds of general formula (I) (exemplified by P-3). A person skilled in the art will recognize that by utilizing differentially substituted amines, a means of obtaining compounds of general formula (I) disclosed herein is possible. [ka] 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-3): [ka] Step 1: 2-Chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(8) To a solution of 5-methoxy-1H-pyrrolo[2,3-b]pyridine (2.40 g, 16.2 mmol) in CH2Cl2 (48 mL), AlCl3 (10.8 g, 81.0 mmol) was added, followed by a solution of chloroacetyl chloride (9.15 g, 81.0 mmol) in CH2Cl2 (7 mL) at 0°C under N2. The reaction mixture was stirred at 0°C for 1 hour and quenched by adding H2O (50 mL). The pH was adjusted to 10 with saturated aqueous Na2CO3 solution. The mixture was filtered through Celite, and the filter cake was washed with siRNA (50 mL x 2). The filtrate was separated, the organic layer was washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The filter cake was stirred in siRNA / THF (1:1, 200 mL) for 12 hours. The mixture was filtered, the filtrate was concentrated and combined with the preceding organic layer to give 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (2.80 g, 77%) as an off-white solid. 1 H NMR (400MHz, DMSO-d6): δ 12.58(br,1H),8.53(s,1H),8.10(d,J=2.8Hz,1H),7.96(d,J=2.8Hz,1H),4.90(s,2H),3.86(s,3H). LCMS(ESI+):m / z225.1, 227.1[M+H] + . HPLC purity (220nm): 100%.

[0302] Step 2: 3-(2-chloroethyl)-5-methoxy-1H-pyrrolo[2,3-b]pyridine(9) To a solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one 8 (1.40 g, 6.23 mmol) in TFA (10 mL), Et3SiH (5.07 g, 43.6 mmol) was added. The reaction mixture was stirred at 25°C for 12 hours. The reaction mixture was adjusted to pH 9 with saturated aqueous Na2CO3 solution and extracted with ELISA (80 mL x 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under vacuum to give crude 3-(2-chloroethyl)-5-methoxy-1H-pyrrolo[2,3-b]pyridine 9 (1.40 g) as an off-white solid. 1 H NMR(400MHz,DMSO-d6):δ 11.29(br,1H),7.94(d,J=2.8Hz,1H),7.60(d,J=2.4Hz,1H),7.32(d,J=2.4Hz,1H),3.82-3.87(m,5H),3.12(t,J=7.4Hz,2H). LCMS(ESI+):m / z211.1, 213.1[M+H] + . HPLC purity (220nm): 98.5%

[0303] Step 3: 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-3) Crude 3- ( To a mixture of 2-chloroethyl)-5-methoxy-1H-pyrrolo[2,3-b]pyridine (1.40 g), NaI (996 mg, 6.65 mmol) was added, and the mixture was stirred at 90°C for 12 hours. The mixture was filtered, and the filter cake was washed with THF (10 mL). The filtrate was evaporated, and the crude product was purified by preparative HPLC (column: Waters Xbridge BEH C18 (250 × 50 mm × 10 μm), mobile phase: [water (aqueous solution of NH3 + NH4HCO3)-ACN], B: 1-30%, 10 min) to obtain 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine P-3 (397 mg, 29% across two steps) as a brown solid. 1H NMR(400MHz,MeOD-d4):δ 7.91(d,J=2.8Hz,1H),7.56(d,J=2.8Hz,1H),7.19(s,1H),3.89(s,3H),2.89-2.93(m,2H),2.63-2.67(m,2H),2.35(s,6H). LCMS(ESI+):R T =0.79 min, m / z220.2[M+H] + . HPLC purity (220nm): 100%.

[0304] Step 3a: 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine hydrochloride (P-3·HCl) To an ice-cold (0°C) solution of 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (100 mg, 0.45 mmol) in anhydrous Et2O (5 mL) and anhydrous EtOH (1 mL), 2 M HCl in Et2O was added dropwise over 10 minutes until the pH of the reaction solution became acidic. The resulting precipitate was collected by filtration and dried overnight in a vacuum dryer to obtain 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine as a white solid hydrochloride salt (78 mg, 68%). 1 H NMR(400MHz,MeOD-d4):δ 7.91(d,J=2.8Hz,1H),7.56(d,J=2.8Hz,1H),7.19(s,1H),3.89(s,3H),2.96-2.87(m,2H),2.69-2.60(m,2H),2.35(s,6H). HPLC purity (220nm): 99.7%.

[0305] Scheme 2: In some situations, alternative synthesis of compounds of general formula (I) was utilized as outlined in Scheme 2. Nucleophilic substitution of the chloride of intermediate 8 with a appropriately substituted amine generated an aminoethane-1-one. Subsequent two-step reduction made it possible to obtain the compound of general formula (I) (exemplified by P-17). Those skilled in the art will recognize that by utilizing differentially substituted amines, it is possible to obtain the compounds of general formula (I) disclosed herein. [ka] 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-diethylethane-1-amine(P-17): [ka] Step 1: 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (40) A solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (250 mg, 1.11 mmol), NaI (250 mg, 1.67 mmol), and Et2NH (814 mg, 11.1 mmol) in DMAc (7 mL) was stirred at ambient temperature for 2 hours. At this point, the reaction mixture was diluted with water (30 mL) and then extracted with siRNA (10 mL x 2). The combined organic matter was washed with brine (40 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give crude 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (281 mg) as a yellow solid, which was used in subsequent steps without purification. LCMS(ESI+)m / z262.2[M+H] + .

[0306] Step 2: 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol(41) To a solution of crude 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (189 mg) in MeOH (5 mL) and H2O (1.6 mL), NaBH4 (3.00 g, 79.3 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with water (10 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (15 mL), dried over Na2SO4, and concentrated under vacuum to give crude 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (170 mg) as an off-white solid, which was used without further purification. LCMS(ESI+)m / z264.2[M+H] + .

[0307] Step 3: 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-diethylethane-1-amine (P-17) To a stirred solution of crude 2-(diethylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (170 mg) and Et3SiH (0.20 mL, 1.25 mmol) in MeCN (4 mL), BF3·Et2O (0.10 mL, 0.80 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with water (5 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (15 mL), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2 / MeOH, v / v, 8 / 1) to obtain 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-diethylethane-1-amine (60 mg, 22% across three steps) as an off-white solid. 1H NMR(300MHz,MeOD-d4):δ 7.95(d,J=2.7Hz,1H),7.62(d,J=2.2Hz,1H)7.33(s,1H),3.89(s,3H),3.36-3.41(m,2H),3.12-3.18(m,2H),1.31(t,J=7.3Hz,6H). LCMS(ESI+):R T =3.33 min, m / z248.3[M+H] + . HPLC purity (220nm): 98.6%.

[0308] 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dipropylethane-1-amine(P-18): [ka] Step 1: 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(42) To a solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (250 mg, 1.11 mmol) and NaI (250 mg, 1.67 mmol) in DMAc (7 mL), dipropylamine (1.13 g, 11.1 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction product was quenched with water (30 mL) and then extracted with siRNA (10 mL x 2). The combined organic layer was washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to give crude 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (350 mg) as a yellow solid, which was used in subsequent steps without purification. LCMS(ESI+)m / z 290.4[M+H] + .

[0309] Step 2: 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol(43) To a solution of crude 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (350 mg) in MeOH (5 mL), NaBH4 (3.00 g, 79.3 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with water (10 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, and concentrated under vacuum to give crude 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (280 mg), which was used without further purification. LCMS(ESI+)m / z 292.3[M+H] + .

[0310] Step 3: 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dipropylethane-1-amine (P-18) To a stirred solution of crude 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (280 mg) and Et3SiH (0.40 mL, 2.50 mmol) in MeCN (6 mL), BF3·Et2O (0.30 mL, 2.43 mmol) was added at ambient temperature, and the mixture was stirred overnight at room temperature. The reaction product was quenched with H2O (5 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (15 mL), then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2 / MeOH, v / v, 8 / 1) to obtain 2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dipropylethane-1-amine (80 mg, 26% across three steps) as an off-white solid. 1H NMR(300MHz,MeOD-d4):δ 7.95(d,J=2.6Hz,1H),7.64(d,J=2.6Hz,1H),7.34(s,1H),3.89(s,3H),3.41-3 .47(m,2H),3.15-3.21(m,6H),1.75(sext,J=7.3Hz,4H),1.00(t,J=7.3Hz,6H). LCMS(ESI+)m / z276.3[M+H] + . HPLC purity (220nm): 97.8%.

[0311] Scheme 3: In some circumstances, the means of obtaining compounds of general formula (I) via Scheme 3 required the introduction of a suitable protecting group for the reactive pyrroloamine. Base-mediated SEM protection of the common intermediate 8 yielded protected aza-indole 44. This intermediate proved adaptable to the aforementioned synthetic route (Scheme 5) involving nucleophilic substitution of the chloride of intermediate 44 with a suitablely substituted amine. Subsequent two-step reduction simultaneously removed the SEM protecting group that provided a means of obtaining compounds of general formula (I) (exemplified by P-19). Those skilled in the art will recognize that by utilizing differentially substituted amines, it is possible to obtain alternative derivatives of general formula (I) disclosed herein. [ka] N-isopropyl-N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)propan-2-amine(P-19): [ka] Step 1: 2-Chloro-1-(5-Methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(44) A solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (1 g, 4.45 mmol) and DIPEA (3.00 mL, 22.0 mmol) in DMAc (10 mL) was treated with (2-(chloromethoxy)ethyl)trimethylsilane (2.50 mL, 14.1 mmol) at 0°C, and then stirred at ambient temperature for 5 hours. The reaction mixture was then quenched with H2O (30 mL) and extracted with  (10 mL × 2). The combined organic layer was washed with brine (40 mL), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to column chromatography (petroleum ether: Â1-7:1) to obtain crude 2-chloro-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (420 mg), which was used in subsequent steps without further purification. LCMS(ESI+): m / z 355.3, 357.2[M+H] + .

[0312] Step 2: 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(45) A solution of crude 2-chloro-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (410 mg), NaI (410 mg, 2.74 mmol), and diisopropylamine (2.07 mL, 14.8 mmol) in DMAc (5 mL) was stirred at ambient temperature for 3 hours. The reaction mixture was quenched with water (30 mL) and then extracted with ethyl acetate (10 mL x 2). The combined organic compounds were washed with brine (40 mL), dried on anhydrous sodium 2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography (petroleum ether / Âti, v / v, 3 / 1) to obtain crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (146 mg). LCMS(ESI+): m / z 420.5[M+H] + .

[0313] Step 3: 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol(46) To a solution of crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (145 mg) in MeOH (2 mL) and H2O (0.4 mL), NaBH4 (3.00 g, 79.3 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with water (10 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (30 mL), dried on anhydrous sodium 2SO4, and concentrated under vacuum to yield crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (110 mg), which was used in subsequent steps without further purification. LCMS(ESI+)m / z422.4[M+H]+ .

[0314] Step 4: N-isopropyl-N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)propan-2-amine(P-19) To a stirred solution of crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (110 mg) and Et3SiH (300 mg, 2.58 mmol) in MeCN (2 mL), BF3·Et2O (0.20 mL, 1.62 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with H2O (5 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (15 mL), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2:MeOH, v / v, 8 / 1) to obtain N-isopropyl-N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)propan-2-amine (20 mg, 2% over four steps) as an off-white solid. 1 H-NMR(300MHz,MeOD-d4):δ 7.96(d,J=2.5Hz,1H),7.55(d,J=2.4Hz,1H),7.36(s,1H),3.89(s,3H),3.79 -3.83(m,2H),3.36-3.41(m,2H),3.13-3.18(m,2H),1.42(d,J=6.6Hz,12H). LCMS(ESI+)m / z276.4[M+H] + . HPLC purity (220nm): 97.4%.

[0315] N-ethyl-2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-methylethane-1-amine(P-20): [ka] Step 1: 2-(ethyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(47) A solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (250 mg, 1.11 mmol), NaI (250 mg, 1.67 mmol), and ethyl(methyl)amine (658 mg, 11.1 mmol) in DMAc (7 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was diluted with water (30 mL) and then extracted with ethyl(dimethyl) (10 mL x 2). The combined organic compounds were washed with brine (40 mL), dried on anhydrous sodium (Na2SO4), and concentrated under reduced pressure to give crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (216 mg) as a yellow solid, which was used in subsequent steps without purification. LCMS(ESI+)m / z 248.3[M+H] + .

[0316] Step 2: 2-(ethyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol(48) To a solution of crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (205 mg) in MeOH / H2O (6 / 2 v / v, 8 mL), NaBH4 (3.00 g, 79.3 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with water (10 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic matter was washed with brine (30 mL), dried on anhydrous Na2SO4, and concentrated under vacuum to give crude 2-(dipropylamino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (185 mg) as a white solid, which was used in the next step without further purification. LCMS(ESI+)m / z250.2[M+H] + .

[0317] Step 3: N-ethyl-2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-methylethane-1-amine(P-20·HCl) To a stirred solution of crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (185 mg) and Et3SiH (0.40 mL, 2.5 mmol) in MeCN (4 mL), BF3·Et2O (0.50 mL, 4.05 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with saturated aqueous Na2CO3 (5 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layer was washed with brine (15 mL), then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2 / MeOH, v / v, 8 / 1). The HCl salt was recovered after treatment with HCl / MeOH (1 mL) to obtain N-ethyl-2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-methylethane-1-amine hydrochloride (30 mg, 12% across three steps) as an off-white solid. 1 H NMR(300MHz,MeOD-d4):δ 8.56(d,J=2.1Hz,1H),8.25(d,J=2.0Hz,1H),7.66(s,1H),4.00(s,3H),3 .33-3.55(m,4H),3.13-3.22(m,2H),2.92(s,3H),1.34(t,J=7.3Hz,3H). . LCMS(ESI+)m / z234.2[M+H] + . HPLC purity (220nm): 98.6%.

[0318] N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylpropan-2-amine(P-21): [ka] Step 1: 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(49) A solution of 2-chloro-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (300 mg, 1.33 mmol), NaI (300 mg, 2.00 mmol), and methyl(propan-2-yl)amine (977 mg, 13.4 mmol) in DMAc (8 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with water (30 mL) and then extracted with  (10 mL x 2). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to give crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (275 mg) as a yellow solid, which was used in subsequent steps without purification. LCMS(ESI+)m / z262.2[M+H] + .

[0319] Step 2: 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol(50) To a solution of crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (275 mg, 1.05 mmol) in MeOH / H2O (8 mL, v / v, 6 / 2), NaBH4 (3.00 g, 79.3 mmol) was added at ambient temperature. The resulting mixture was stirred overnight at ambient temperature. The reaction product was quenched with water (10 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium 2SO4, and concentrated under vacuum to yield crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (207 mg) as a white solid, which was used in the next step without further purification. LCMS(ESI+)m / z 264.3[M+H] + .

[0320] Step 3: N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylpropan-2-amine(P-21) To a stirred solution of crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-ol (207 mg) and Et3SiH (0.40 mL, 2.50 mmol) in MeCN (4 mL), BF3·Et2O (0.30 mL, 2.43 mmol) was added at ambient temperature, and the mixture was stirred overnight. The reaction product was quenched with saturated aqueous Na2CO3 (5 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 2 × 5 mL). The combined organic layer was washed with brine (10 mL), dried on anhydrous Na2SO4, and concentrated under vacuum. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2 / MeOH, v / v, 8 / 1) to obtain N-(2-(5-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylpropan-2-amine (32 mg, 10% across three steps) as an off-white solid. 1 H NMR(300MHz,MeOD-d4):δ 7.95(d,J=2.4Hz,1H),7.65(d,J=2.5Hz,1H),7.34(s,1H),3.89(s,3H),3.64-3.72 (m,1H),3.34-3.44(m,2H),3.12-3.23(m,2H),2.85(s,3H),1.32(d,J=6.0Hz,6H). LCMS(ESI+)m / z248.3[M+H] + . HPLC purity (220nm): 96%.

[0321] N,N-dimethyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-22): [ka] Step 1: 2-Chloro-1-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (52) A mixture of 5-methyl-1H-pyrrolo[2,3-b]pyridine (500 mg, 3.78 mmol) in CH2Cl2 (15 mL) was degassed, purged three times with N2, and then AlCl3 (2.52 g, 18.9 mmol) was added at 0°C under N2. After stirring at 0°C for 5 minutes, 2-chloroacetyl chloride (1.28 g, 11.3 mmol) was added at 0°C, and the mixture was then stirred at ambient temperature for 2 hours. The reaction product was quenched with water (15 mL) at 0°C, then adjusted to pH 9 with aqueous Na2CO3 solution, filtered, and the filter cake was washed with RINKAN (30 mL x 4). The aqueous phase was separated and extracted with RINKAN (20 mL x 3). The combined organic compounds were washed with brine (10 mL x 2), dried on anhydrous sodium 2SO4, and concentrated under reduced pressure to obtain crude 2-chloro-1-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (650 mg) as a yellow solid, which was used in the next step without purification.

[0322] Step 2: 3-(2-chloroethyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine(53) To a solution of 2-chloro-1-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (650 mg) in TFA (10 mL), Et3SiH (5.10 g, 43.9 mmol) was added, and the reaction mixture was stirred at 70°C for 12 hours. The reaction mixture was then concentrated under reduced pressure, and the residue was adjusted to pH 9 with saturated Na2CO3 solution. It was then extracted with  (10 mL x 3). The combined organic compounds were washed with brine (10 mL x 2), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / Â, v / v, 10:1~1:1) to obtain 3-(2-chloroethyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine (350 mg) as an off-white solid. LCMS(ESI+)m / z 195.1[M+H] + .

[0323] Step 3: 2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (P-22) To a solution of 3-(2-chloroethyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine (200 mg) in THF (3 mL), NaI (462 mg, 3.08 mmol) and 2 M Me2NH in THF (1.03 mL, 2.06 mmol) were added, and the mixture was stirred in a sealed tube at 90°C for 12 hours. The reaction mixture was diluted with water (20 mL) and then extracted with ₹ (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water(NH3)-ACN]; B: 12-42%, 9 min), 2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (25 mg, 6% over three steps) was obtained as an off-white solid. 1 H NMR(400MHz,CDCl3):δ 9.11(br s,1H),8.13(d,J=2.0Hz,1H),7.71(s,1H),7.10(s,1H),2.89-2.93(m,2H),2.62-2.66(m,2H),2.44(s,3H),2.36(s,6H). LCMS(ESI+)m / z204.0[M+H] + . HPLC purity (220nm): 96.5%

[0324] N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-23): [ka] Step 1: N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-23) To a solution of 3-(2-chloroethyl)-5-methyl-1H-pyrrolo[2,3-b]pyridine (200 mg, 1.03 mmol) in DMF (3 mL), K2CO3 (213 mg, 1.54 mmol) and ethyl(methyl)amine (182 mg, 3.08 mmol) were added, and the mixture was stirred at 50°C for 12 hours. The reaction mixture was diluted with water (20 mL) and then extracted with  (5 mL × 3). The combined organic compounds were washed with brine (5 mL × 2), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water (NH4HCO3)-ACN]; B: 12-42%, 9 min), N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (25 mg, 5% over three steps) was obtained as an off-white solid. 1 H NMR(400MHz,CDCl3):δ 9.08(br s,1H),8.14(d,J=1.6Hz,1H),7.72(s,1H),7.11(s,1H),2.99-2.86(m,2H),2.76-2 .67(m,2H),2.57(q,J=7.2Hz,2H),2.45(s,3H),2.38(s,3H),1.13(t,J=7.2Hz,3H). LCMS(ESI+)m / z218.0[M+H] + . HPLC purity (220nm): 98.2%.

[0325] N,N-dimethyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-24): [ka] Step 1: 2-Chloro-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (55) A mixture of 5-fluoro-1H-pyrrolo[2,3-b]pyridine (1.00 g, 7.35 mmol) in CH2Cl2 (7 mL) was degassed, purged three times with N2, and then AlCl3 (4.90 g, 36.8 mmol) was added at 0°C under N2. After stirring at 0°C for 5 minutes, 2-chloroacetyl chloride (4.15 g, 36.7 mmol) was added at 0°C, and the mixture was then stirred at ambient temperature for 3 hours. The reaction was then quenched with water (20 mL) at 0°C, the pH was adjusted to 9 with aqueous Na2CO3 solution, and then filtered. The filtered cake was washed with siRNA (30 mL x 4), the aqueous phase was separated, diluted with H2O (30 mL), and further extracted with siRNA (20 mL x 3). The combined organic matter was washed with brine (50 mL), dried on anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain crude 2-chloro-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (1.16 g) as a yellow solid, which was used in the next step without purification.

[0326] Step 2: 3-(2-chloroethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(56) To a solution of 2-chloro-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (1.16 g, 5.46 mmol) in TFA (10 mL), Et3SiH (3.64 g, 31.3 mmol) was added, and the reaction mixture was stirred at ambient temperature for 12 hours. The reaction mixture was adjusted to pH 9 with saturated Na2CO3 solution, diluted with H2O (50 mL), and then extracted with ELISA (75 mL x 3). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was pulverized with MTBE:petroleum ether (1:5 v / v, 20 mL) at ambient temperature for 30 minutes, filtered, and 3-(2-chloroethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (389 mg) was obtained as a yellow solid. LCMS(ESI+)m / z199.0[M+H] + ;

[0327] Step 3: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-24) To a solution of 3-(2-chloroethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (50.0 mg, 0.25 mmol) in THF (5 mL), NaI (56.6 mg, 0.39 mmol) and 2 M Me2NH in THF (0.5 mL, 1.01 mmol) were added, and the mixture was stirred in a sealed tube at 100°C for 12 hours. The reaction mixture was then diluted with water (20 mL) and extracted with ₹ (20 mL × 5). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water(NH3)-ACN]; B: 18-48%, 10 min), 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (10.3 mg, 5% over three steps) was obtained as a yellow solid. 1 H NMR(400MHz,CDCl3):δ 9.11(br,1H),8.17(t,J=2.2Hz,1H),7.60(dd,J=8.9,2.7Hz,1H),7.21(d,J=2.4Hz,1H),2.89(t,J=7.6Hz,2H),2.62(t,J=6.9Hz,2H),2.35(s,6H). 19 F NMR (400MHz, CDCl3): δ -139.4. LCMS(ESI+)m / z208.2[M+H] + . HPLC purity (220nm): 98.0%.

[0328] N-ethyl-N-methyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-25): [ka] Step 1: N-ethyl-N-methyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-25) To a solution of 3-(2-chloroethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (200 mg, 1.01 mmol) in DMF (5 mL), K2CO3 (306 mg, 2.21 mmol) and ethyl(methyl)amine (238 mg, 4.03 mmol) were added, and the mixture was stirred in a sealed tube at 50°C for 12 hours. The reaction mixture was then diluted with water (20 mL) and extracted with ₹ (20 mL × 5). The combined organic compounds were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * The solution was purified by a 5 μm mobile phase (water (aqueous NH3)-ACN); B: 18-48%, 10 min) to obtain N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (57.0 mg, 7% over three steps) as a yellow solid. 1 H NMR(400MHz,CDCl3):δ 9.19(br s,1H),8.16(t,J=2.2Hz,1H),7.61(dd,J=8.9,2.6Hz,1H),7.20(d,J=2.1Hz,1H),2.87-2 .91(m,2H),2.66-2.70(m,2H),2.53(q,J=7.2Hz,2H),2.34(s,3H),1.11(t,J=7.2Hz,3H). 19 F NMR (400MHz, CDCl3): δ -139.4. LCMS(ESI+)m / z222.2[M+H] + . HPLC purity (220nm): 98.0%.

[0329] Scheme 4: Compounds of general formula (I) can be synthesized from appropriately substituted aza-indole according to the outlined sequence of steps in Scheme 4 or similar to those that a person skilled in the art could consider. By Friedel-Crafts acylation of aza-indole starting material 10 in a manner similar to the steps outlined in Scheme 4, a means is provided to obtain intermediate 11 that can be subjected to chemoselective silane reduction conditions to provide alkyl chloride intermediate 12. By nucleophilic substitution of alkyl chloride with substituted amine, compounds of general formula (I) (exemplified by P-4) are provided. [ka] 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-4): [ka] Step 1: 2-Chloro-1-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(11) To a solution of 4-methoxy-1H-pyrrolo[2,3-b]pyridine (2.20 g, 14.8 mmol) in CH2Cl2 (14 mL), AlCl3 (9.90 g, 74.2 mmol) and chloroacetyl chloride (8.39 g, 74.2 mmol) were added. The mixture was stirred at 0°C for 1.5 hours. The reaction mixture was quenched by adding H2O (20 mL) at 0°C, and then adjusted to pH 9 with saturated aqueous Na2CO3 solution. The mixture was filtered and extracted with siRNA (50 mL x 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and set aside. The filtered cake was pulverized with THF / siRNA (1:1, 100 mL) at 20°C for 2 hours. The filtrate was combined with the organic layer and concentrated in a vacuum to give the title compound (3.10 g, 93%) as a pale yellow solid. 1H NMR:(400MHz,DMSO-d6):δ 12.5(br s,1H),8.27(s,1H),8.21(d,J=5.6Hz,1H),6.84(d,J=5.6Hz,1H),4.97(s,2H),3.95(s,3H). LCMS(ESI+)m / z225.1[M+H] + .

[0330] Step 2: 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine(12) To a solution of 2-chloro-1-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (2.26 g, 10.1 mmol) in TFA (13.2 mL), Et3SiH (8.19 g, 70.4 mmol) was added. The mixture was stirred at 20°C for 16 hours. The reaction mixture was adjusted to pH=9 with saturated aqueous Na2CO3 solution and then extracted with siRNA (50 mL x 2). The combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under vacuum to give 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine(12) (2.00 g, 94%) as a red solid. 1 H NMR:(400MHz,DMSO-d6):δ 8.06(d,J=5.6Hz,1H),7.14(d,J=1.6Hz,1H),6.63(d,J=5.6Hz,1H),5.20(br s,1H),3.93(s,3H),3.81(t,J=7.4Hz,2H),3.16(t,J=7.4Hz,2H). LCMS(ESI+)m / z211.1[M+H] + .

[0331] Step 3: 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-4) A solution of 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine (1.6 g, 7.6 mmol) in 2 M Me2NH in THF (32.3 mL, 8.5 equivalents, 64.6 mmol) was treated with sodium iodide (1.14 g, 7.6 mmol) and stirred under reflux for 24 hours. After completion, the reaction mixture was filtered, and the filtrate cake was eluted with THF (20 mL). The combined filtrate was concentrated under vacuum, and the residue was separated and HPLC (column: Waters Xbridge Prep OBD C18 150) was performed. * 40mm * The mixture was purified using a 10 μm mobile phase (water (NH4HCO3)-ACN), with B being 1% to 30% for 8 minutes, to obtain 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (0.6 g, 2.74 mmol) as a pale yellow solid (600 mg, 36%). 1 H-NMR(400MHz,MeOD-d4):δ 8.03(d,J=5.6Hz,1H),7.00(s,1H),6.64(d,J=5.6Hz,1H),4.00(s,3H),2.96-3.03(m,2H),2.60-2.68(m,2H),2.34(s,6H). LCMS(ESI+)m / z220.2[M+H] + . HPLC purity (220nm): 100%.

[0332] Step 3a: 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine hydrochloride (P-4·HCl) To an ice-cold (0°C) solution of 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (0.2 g, 0.91 mmol) in anhydrous Et2O (5 mL) and anhydrous EtOH (1 mL), 2 M HCl in Et2O was added dropwise over 10 minutes until the pH of the reaction solution became acidic. The resulting precipitate was collected by filtration and dried overnight in a vacuum dryer to obtain 2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine as a white solid hydrochloride salt (120 mg, 52%). 1H NMR(400MHz,DMSO-d6):δ 12.47(s,1H),10.55(br.s,1H),8.38(d,J=6.6Hz,1H),7.40(d,J=2.2Hz,1H), 7.07(d,J=6.6Hz,1H),4.15(s,3H),3.30-3.16(m,4H),2.81(d,J=4.8Hz,6H). 13 C NMR (100MHz, DMSO-d6): δ 164.3,142.3,138.8,124.1,111.1,110.1,99.1,57.2,57.1,42.1,21.0. HPLC purity (220nm): 96.7%.

[0333] N,N-diethyl-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-26) [ka] To a solution of 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine (500 mg, 2.37 mmol) in THF (5 mL), NaI (534 mg, 3.56 mmol) and Et2NH (1.74 g, 23.8 mmol) were added, and the mixture was stirred at 100°C for 48 hours. The mixture was then filtered, and the filtrate cake was washed with THF (5 mL). The filtrate was concentrated under reduced pressure, and the residue was separated and subjected to preparative HPLC (column: Waters Xbridge (150)). * 25mm * The mixture was purified using a 5 μm mobile phase (water (NH4HCO3)-ACN); B: 5-35%, 9 min) to obtain N,N-diethyl-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-26) (100 mg, 17%) as a pale yellow solid. 1 H NMR(400MHz,MeOD-d4):δ 8.05(d,J=5.7Hz,1H),7.02(s,1H),6.66(d,J=5.7Hz,1H),4.02(s,3H),2.97- 3.02(m,2H),2.81-2.85(m,2H),2.74(q,J=7.2Hz,4H),1.16(t,J=7.2Hz,6H). LCMS(ESI+)m / z248.1[M+H]+ . HPLC purity (220nm): 96.9%.

[0334] N-isopropyl-N-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)propan-2-amine(P-27) [ka] To a solution of 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine (500 mg, 2.37 mmol) in THF (5 mL), NaI (534 mg, 3.56 mmol) and diisopropylamine (2.40 g, 23.7 mmol) were added, and the mixture was stirred at 100°C for 48 hours. The mixture was then filtered, and the filtrate was washed with THF (5 mL). The filtrate was concentrated under reduced pressure, and the residue was separated and subjected to preparative HPLC (column: Waters Xbridge (150)). * 25mm * The mixture was purified using a 5 μm mobile phase (water (NH4HCO3)-ACN); B: 10-40%, 9 min) to obtain N-isopropyl-N-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)propan-2-amine (P-27) (14.4 mg, 2%) as a pale yellow solid. 1 H NMR(400MHz,MeOD-d4):δ 8.04(br d,J=3.2Hz,1H),7.00(s,1H),6.65(d,J=5.7Hz,1H),4.00(s,3H),3.16(hept ,J=6.5Hz,2H),2.90-2.94(m,2H),2.72-2.77(m,2H),1.14(d,J=6.5Hz,12H). LCMS(ESI+)m / z276.1[M+H] + . HPLC purity (220nm): 97.1%.

[0335] N-ethyl-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-methylethane-1-amine(P-28) [ka] To a solution of 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine (200 mg, 0.95 mmol) in THF (2 mL), NaI (213 mg, 1.42 mmol) and ethyl(methyl)amine (561 mg, 9.49 mmol) were added, and the mixture was stirred at 100°C for 48 hours. The mixture was then filtered, and the filtrate was washed with THF (2 mL). The filtrate was concentrated under reduced pressure, and the residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * The mixture was purified using a 5 μm mobile phase (water (NH4HCO3)-ACN); B: 5-35%, 9 min) to obtain N-ethyl-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-methylethane-1-amine (P-28) (64.0 mg, 29%) as a pale yellow solid. 1 H NMR(400MHz,MeOD-d4):δ 8.07(d,J=5.7Hz,1H),7.08(s,1H),6.68(d,J=5.7Hz,1H),4.03(s,3H),3.06-3.14( m,2H),2.96-3.03(m,2H),2.87(q,J=7.2Hz,2H),2.60(s,3H),1.23(t,J=7.2Hz,3H). LCMS(ESI+)m / z233.15[M+H] + . HPLC purity (220nm): 96.9%.

[0336] N-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylpropan-2-amine(P-29) [ka] To a solution of 3-(2-chloroethyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine (150 mg, 0.71 mmol) in THF (2 mL), NaI (160 mg, 1.07 mmol) and methyl(propan-2-yl)amine (521 mg, 7.12 mmol) were added, and the mixture was stirred at 100°C for 48 hours. The mixture was filtered, and the filter cake was washed with THF (1.5 mL). The filtrate was concentrated under reduced pressure, and the residue was separated by preparative HPLC (column: Waters Xbridge Prep OBD C18 (150)). * 40mm * The mixture was purified using a 10 μm mobile phase (water (NH4HCO3)-ACN); B: 0-30%, 15 min) to obtain N-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylpropan-2-amine (P-29) (120 mg, 68%) as a pale yellow solid. 1 H NMR(400MHz,MeOD-d4):δ 8.04(d,J=5.7Hz,1H),7.01(s,1H),6.65(d,J=5.7Hz,1H),4.01(s,3H),2 .95-3.00(m,3H),2.71-2.76(m,2H),2.37(s,3H),1.10(d,J=6.5Hz,6H). LCMS(ESI+)m / z248.1[M+H] + . HPLC purity (220nm): 96.2%.

[0337] N,N-dimethyl-2-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-30): [ka] Step 1: 2-Chloro-1-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (58) A mixture of 4-methyl-1H-pyrrolo[2,3-b]pyridine (500 mg, 3.78 mmol) in CH2Cl2 (15 mL) was degassed, purged three times with N2, and then AlCl3 (2.52 g, 18.9 mmol) was added at 0°C under N2. After stirring at 0°C for 5 minutes, 2-chloroacetyl chloride (1.28 g, 11.3 mmol) was added at 0°C, and the mixture was then stirred at room temperature under N2 for 2 hours. The reaction mixture was then cooled to 0°C, then quenched with water (20 mL), and subsequently saturated aqueous Na2CO3 was added until the solution reached pH 9. The mixture was then filtered, the filter cake was washed with toluene (30 mL x 4), the aqueous phase was separated, and extracted with toluene (20 mL x 3). The combined organic compounds were washed with brine (15 mL x 2), dried on anhydrous sodium 2SO4, filtered, and the filtrate was concentrated under reduced pressure to obtain crude 2-chloro-1-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (58) (850 mg) as a yellow solid, which was used in the next step without purification.

[0338] Step 2: 3-(2-chloroethyl)-4-methyl-1H-pyrrolo[2,3-b]pyridine (59) To a solution of 2-chloro-1-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (800 mg) in TFA (10 mL), Et3SiH (4.11 g, 35.3 mmol) was added, and the reaction mixture was stirred at 70°C for 12 hours. The reaction mixture was then concentrated under reduced pressure, and the residue was adjusted to pH 9 with saturated aqueous Na2CO3 solution, and then extracted with siRNA (10 mL x 3). The combined organic matter was washed with brine (10 mL x 2), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether: siRNA 10:1~1:2) to obtain 3-(2-chloroethyl)-4-methyl-1H-pyrrolo[2,3-b]pyridine (59) (310 mg, 42% across two steps) as a white solid. LCMS(ESI+): m / z 195.0

[0339] Step 3: N,N-dimethyl-2-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-30) A mixture of 3-(2-chloroethyl)-4-methyl-1H-pyrrolo[2,3-b]pyridine (50.0 mg, 257 μmol), K2CO3 (53.3 mg, 0.39 mmol), and Me2NH (23.3 mg, 0.52 mmol) in THF (4 mL) and DMF (2 mL) was stirred in a sealed tube at 50°C for 12 hours. The reaction mixture was then diluted with water (20 mL) and extracted with ₹ (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * The mixture was purified using a 5 μm mobile phase (water (NH3)-ACN), with B being 18-48% for 10 minutes, to obtain N,N-dimethyl-2-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-30) (15.0 mg, 14%) as a white solid. 1 H NMR(400MHz,CDCl3):δ 8.84(br s.,1H),8.13(d,J=4.8Hz,1H),7.08(br s, 1H), 6.82 (d, J=4.8Hz, 1H), 3.07-3.11 (m, 2H), 2.70 (s, 3H) 2.65-2.69 (m, 2H), 2.39 (s, 6H). LCMS(ESI+):m / z204.0. HPLC purity (220nm): 99.6%.

[0340] N-ethyl-N-methyl-2-(4-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-31): [ka] Step 1: N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-31) To a solution of 3-(2-chloroethyl)-4-methyl-1H-pyrrolo[2,3-b]pyridine (150 mg, 771 μmol) in DMF (3 mL), K2CO3 (160 mg, 1.16 mmol) and ethyl(methyl)amine (137 mg, 2.32 mmol) were added, and the mixture was stirred at 50°C for 12 hours. The reaction mixture was then diluted with water (20 mL) and extracted with RINKAN (5 mL x 3). The combined organic compounds were washed with brine (5 mL x 2), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water (NH4HCO3)-ACN]; B: 10-40%, 9 min), N-ethyl-N-methyl-2-(5-methyl-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-31) (30.0 mg, 18%) as an off-white solid. 1 H NMR(400MHz,CDCl3)δ 9.32(br s,1H),8.13(d,J=4.8Hz,1H),7.09(s,1H),6.82(d,J=4.9Hz,1H),3.07-3.11(m,2H),2. 69-2.73(m,2H),2.71(s,3H),2.57(q,J=7.1Hz,2H),2.38(s,3H),1.13(t,J=7.2Hz,3H). LCMS(ESI+)m / z218.0[M+H] + . HPLC purity (220nm): 96.7%.

[0341] N,N-dimethyl-2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-32): [ka] Step 1: 2-Chloro-1-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (61) A mixture of 4-fluoro-1H-pyrrolo[2,3-b]pyridine (700 mg, 5.14 mmol) in CH2Cl2 (15 mL) was degassed, purged three times with N2, and then AlCl3 (3.43 g, 25.7 mmol) was added at 0°C under N2. After stirring at 0°C for 5 minutes, 2-chloroacetyl chloride (2.90 g, 25.7 mmol) was added at 0°C, and the mixture was then stirred at ambient temperature under an N2 atmosphere for 6 hours. The reaction product was then cooled to 0°C, quenched with water (20 mL), adjusted to pH 9 with saturated aqueous solution Na2CO3, and then filtered. The filtered cake was washed with siRNA (30 mL x 4), the aqueous phase was separated, diluted with water (30 mL), and extracted with siRNA (20 mL x 3). The combined organic compounds were washed with brine (50 mL), dried on anhydrous sodium 2SO4, and concentrated under reduced pressure to obtain crude 2-chloro-1-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (61) (727 mg) as a yellow solid, which was used in the next step without purification.

[0342] Step 2: 3-(2-chloroethyl)-4-fluoro-1H-pyrrolo[2,3-b]pyridine(62) To a solution of 2-chloro-1-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (700 mg) in TFA (10 mL), Et3SiH (2.91 g, 25.0 mmol) was added, and the reaction mixture was stirred at 25°C for 12 hours. The reaction mixture was adjusted to pH 9 with saturated aqueous solution Na2CO3, diluted with H2O (50 mL), and then extracted with ELISA (75 mL x 3). The combined organic matter was washed with brine (50 mL), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was pulverized with 1:5 MTBE / petroleum ether (1 / 5 v / v, 20 mL) for 30 minutes at ambient temperature, filtered, and crude 3-(2-chloroethyl)-4-fluoro-1H-pyrrolo[2,3-b]pyridine (62) (580 mg) was obtained as a yellow solid. LCMS(ESI+)m / z199.1[M+H] + .

[0343] Step 3: 2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine(P-32) To a solution of crude 3-(2-chloroethyl)-4-fluoro-1H-pyrrolo[2,3-b]pyridine (200 mg) in DMF (5 mL), K2CO3 (306 mg, 2.21 mmol) and 2 M dimethylamine in THF (2.01 mL) were added, and the mixture was stirred in a sealed tube at 50°C for 12 hours. The reaction mixture was diluted with water (20 mL) and then extracted with ₹ (20 mL × 5). The combined organic matter was washed with brine (50 mL), dried on anhydrous Na2SO4, and concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water(NH3)-ACN]; B: 18-48%, 10 min), 2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N,N-dimethylethane-1-amine (P-32) (34.1 mg, 10% over three steps) was obtained as a yellow solid. 1 H NMR(400MHz,CDCl3):δ 9.15(br s,1H),8.21(dd,J=7.8,5.5Hz,1H),7.11(s,1H),6.77(dd,J=10.3,5.5Hz,1H),3.02-3.06(m,2H),2.69-2.73(m,2H),2.39(s,6H). 19 F NMR (400MHz, CDCl3): δ -112.5. LCMS(ESI+)m / z208.2[M+H] + . HPLC purity (220nm): 96.6%.

[0344] N-ethyl-N-methyl-2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-33): [ka] Step 1: N-ethyl-N-methyl-2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-33) To a solution of crude 3-(2-chloroethyl)-4-fluoro-1H-pyrrolo[2,3-b]pyridine (200 mg) in DMF (5 mL), K2CO3 (306 mg, 2.21 mmol) and ethyl(methyl)amine (238 mg, 4.03 mmol) were added, and the mixture was stirred in a sealed tube at 50°C for 12 hours. The reaction mixture was then diluted with water (20 mL) and extracted with ₹ (20 mL × 5). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by preparative HPLC (column: Waters Xbridge (150)). * 25mm * Purified by (5 μm); mobile phase: [water(NH3)-ACN]; B: 20-50%, 10 min), N-ethyl-N-methyl-2-(4-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (P-33, 34.1 mg, 9% over three steps) was obtained as a pink solid. 1 H NMR(400MHz,CDCl3):δ 9.25(br s,1H),8.21(dd,J=7.7,5.5Hz,1H),7.10(s,1H),6.77(dd,J=10.3,5.5Hz,1H),3.01-3. 05(m,2H),2.74-2.77(m,2H),2.59(q,J=7.0Hz,2H)2.39(s,3H),1.13(t,J=7.2Hz,3H). 19 F NMR (400MHz, CDCl3): δ -112.4. LCMS(ESI+)m / z222[M+H] + . HPLC purity (220nm): 98.8%.

[0345] The following compounds S1 to S75 can be prepared by a similar route. [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]

[0346] overview In the following examples, unless otherwise stated, temperatures are given in degrees Celsius (°C), operations are carried out at room temperature or ambient temperature, "room temperature (rt)" or "room temperature (RT)" (typically in the range of approximately 18–25°C), solvent evaporation is carried out under reduced pressure using a rotary evaporator (typically 4.5–30 mm Hg) at a bath temperature of up to 60°C, thin-layer chromatography (TLC) is typically performed after the reaction, the melting point is not corrected, and the product is satisfactory. 1 ¹H NMR and / or trace analysis data are shown, and the following conventional abbreviations are also used: L (liter), mL (milliliters), mmol (millimoles), g (grams), mg (milligrams), min (minutes), and h (hours).

[0347] Unless otherwise specified, all solvents and reagents were purchased from suppliers and used without further purification. Unless otherwise stated, reactions were carried out under a nitrogen blanket. Compounds were visualized under a UV lamp (254 nm). 1 ¹H NMR spectra were recorded on NMR instruments at 300 MHz, 400 MHz, or 600 MHz as instructed. Column and flash chromatography were performed using SiO2 as the stationary phase, where "MeOH / NH3" refers to a 9:1 methanol / 15 M aqueous ammonia solution. LC-MS was performed under the following conditions. [Table 14]

[0348] Compounds of general formula (I) can be synthesized from appropriately substituted 6,5-aromatic systems by following steps similar to those outlined in Schemes 5 and 6 below or those that can be considered by those skilled in the art. Various substituted 6,5-aromatic systems can be commercially available or prepared by techniques known in the art, for example, as described in Whelligan D et al (Journal of Organic Chemistry, Volume 75, 1 January 2010, Pages 11-15).

[0349] Compounds of general formula (I) can be synthesized from appropriately substituted 6,5-aromatic systems by following steps similar to those outlined in schemes 5 and 6 below or steps that a person skilled in the art could consider.

[0350] Scheme 5: Compounds of general formula (I) can be synthesized via appropriately substituted 1H-pyrrolo[2,3-b]pyridine systems according to the outlined sequence of steps in Scheme 5 or similar to those that can be considered by those skilled in the art. Amination of appropriately 5-substituted 2-chloropyridine can be achieved by palladium-catalyzed cross-coupling with diphenylmethanimine, followed by hydrolysis under acidic conditions to obtain Int. 1. Region-selective bromination allows for alkynylation via Sonogashira coupling to obtain Int. 3. Cyclization under basic conditions yields substituted 1H-pyrrolo[2,3-b]pyridine Int. 4, which can be acylated using the Friedel-Crafts method. Reduction and subsequent nucleophilic substitution allow access to compounds of general formula (I). [ka] Scheme 6: Compounds of general formula (I) can be synthesized from similar alkyl halides as outlined in the following steps or as can be considered by those skilled in the art. Access to the primary amine intermediate can be achieved via Gabriel synthesis, which can then be subjected to sequential reductive alkylation with the desired carbonyl and reducing agent to obtain compounds of general formula (I) (as illustrated by Example S30). [ka] General Procedure A: Preparation of 2-halo-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol AlCl3 (3.5 equivalents) was added in small increments to an ice-cold solution of appropriately substituted 1H-pyrrolo[2,3-b]pyridine (1 equivalent) in anhydrous CH2Cl2 (5 mL per 1 mmol of 1H-pyrrolo[2,3-b]pyridine). The reaction mixture was heated under reflux, and a solution of bromoacetyl bromide or chloroacetyl chloride (1 equivalent) in anhydrous CH2Cl2 (1 mL per acyl halide) was added dropwise over 10 minutes. The reaction mixture was stirred under reflux for 1 hour, at which point it was cooled to room temperature and poured onto ice. The crude product was obtained by filtration or extraction with siRNA (3 × 10⁻⁵ V), and the resulting precipitate was collected. The crude product was then purified by column chromatography (20% to 50% siRNA in hexane) to obtain the desired compound.

[0351] General Procedure B: Preparation of 2-haloethyl-1H-pyrrolo[2,3-b]pyridine A solution of appropriately substituted 1H-pyrrolo[2,3-b]pyridine-3-yleuthanone (1 equivalent) in Et3SiH (1 mL per 1 mmol) and trifluoroacetic acid (1 mL per 1 mmol) was heated to 70°C for up to 16 hours. The reaction mixture was quenched by adding saturated NaHCO3 until slightly alkaline (pH = 8-9), and extracted with Et2O (1.5V). The combined organic compounds were washed with brine, dried over Na2SO4 or MgSO4, filtered, and the filtrate was concentrated by rotary evaporation. The resulting crude was then purified by column chromatography (0%-10% HCl in hexane) to obtain the desired compound.

[0352] General procedure C: Alkylation of 2-haloethyl-1H-pyrrolo[2,3-b]pyridine using a free base amine. A pressure tube containing a solution (2 mL per mmol) of appropriately substituted alkyl halide (1 equivalent) and NaI (1 equivalent) in DMF was mixed with appropriately substituted amine (3 equivalents), and the sealed container was heated to 70°C until complete. The reaction mixture was then cooled, poured into H2O (10V), diluted with saturated aqueous Na2CO3 (5V), adjusted to pH 12, and 15% aqueous NaOH was added dropwise. The mixture was then extracted with SiO2 (3 × 10V). Subsequently, the combined organic matter was washed with saturated aqueous Na2CO3 (5 × 2V), H2O (1 × 2V), and brine (2 × 4V), then dried (Na2SO4 or MgSO4), filtered, and the filtrate was concentrated under reduced pressure. The resulting crude mass was then purified by column chromatography (0.1% to 10% MeOH / NH3 in CH2Cl2) to obtain the desired product.

[0353] General procedure D: Alkylation of 2-haloethyl-1H-pyrrolo[2,3-b]pyridine using amine hydrochloride. A pressure tube containing a solution (2 mL per mmol) of appropriately substituted alkyl halide (1 equivalent) and NaI (1 equivalent) in DMF was mixed with appropriately substituted amine hydrochloride (1.3-1.5 equivalents) and iPr2NEt (3 equivalents). The sealed container was heated to 70°C until complete. The reaction mixture was then cooled, poured into H2O (10V), diluted with saturated aqueous Na2CO3 (5V), adjusted to pH 12, and 15% aqueous NaOH was added dropwise. The mixture was then extracted with SiO2 (3 × 10V). The combined organic matter was then washed with saturated aqueous Na2CO3 (5 × 2V), H2O (1 × 2V), and brine (2 × 4V), dried (Na2SO4 or MgSO4), filtered, and the filtrate was concentrated under reduced pressure. The resulting crude was then purified by column chromatography (0.1%-10% MeOH / NH3 in CH2Cl2) to obtain the desired product.

[0354] General Procedure E: Formulation of hydrochloride salts from amines The starting free base amine was dissolved in a minimal amount of solvent (MeOH, iPrOH, or a mixture thereof), and concentrated HCl (37%) was added dropwise to acidify the solution to pH 1. Precipitation was initiated by adding Et2O, and the mixture was left to stand at 0°C. The product was recovered by vacuum filtration and washed with Et2O.

[0355] General Procedure F: Formulation of fumaric acid and maleate from amines A solution of free base amine in a minimal amount of solvent (acetone or iPrOH) was added to a high-temperature solution (1-3 equivalents, 0.02-0.2 M) of fumaric acid or maleic acid in acetone or iPrOH, and the mixture was heated between 40 and 60°C. The mixture was cooled, precipitation was initiated by adding Et2O or hexane, and then allowed to stand at 0°C. The product was recovered by vacuum filtration and washed with Et2O.

[0356] Example 1: Synthesis of N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylcyclopropanamine (S1): [ka] Step 1: 2-Bromo-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(64) The title compound was synthesized using 5-fluoro-1H-pyrrolo[2,3-b]pyridine (2.28 g, 16.7 mmol) according to general procedure A, yielding the title compound as a light brown solid (2.2 g, 51%). 1 H NMR (400MHz, CDCl3): δ 10.22 (s, 1H), 8.45 (dd, J=8.5, 2.7Hz, 1H), 8.34-8.28 (m, 1H), 8.18 (s, 1H), 4.31 (s, 2H).

[0357] Step 2: 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(65) The title compound was synthesized using 2-bromo-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one (1 g, 3.9 mmol) according to general procedure B, and the title compound was obtained as a white crystalline needle (0.8 g, 85%). 1 H NMR(400MHz,DMSO-d6):δ 11.64(s,1H),8.24-8.12(m,1H),8.00-7.90(m,1H),7.49(d,J=2.6Hz,1H),3.75(t,J=7.3Hz,2H),3.23(td,J=7.3,0.8Hz,2H); 13 C NMR (101MHz, DMSO-d6): δ155.3(d,J=238.4Hz),145.8,131.1(d,J=29.0Hz),12 7.2,119.6(d,J=6.9Hz),112.9(d,J=20.6Hz),111.5(d,J=4.3Hz),34.7,29.0.

[0358] Step 3: N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylcyclopropanamine hydrochloride (S1·HCl) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.4 g, 1.65 mmol), N-methylcyclopropanamine hydrochloride (266 mg, 2.5 mmol), and iPr2NEt (0.86 mL, 4.9 mmol). During purification, the title compound was produced as a colorless oil (293 mg, 76%), and subsequently formulated as a white crystalline solid hydrochloride according to general procedure E (180 mg, 54%). LCMS (condition A): t R (3.210 minutes) m / z=234.15[M+H] + ; 1H NMR(400MHz,DMSO-d6):δ 11.69(s,1H),10.78(s,1H),8.21(dd,J=2.8,1.7Hz,1H),8.02(dd,J=9.6,2.8Hz,1H),7.51(d,J=2.5Hz,1H),3. 49-3.40(m,2H),3.31-3.12(m,2H),2.97-2.86(m,4H),1.30-1.19(m,1H),1.10-0.99(m,1H),0.96-0.76(m,2H); 13 C NMR(101MHz,DMSO-d6):δ 155.2(d,J=238.6Hz),145.9,131.5,127.0,119.5(d,J=6.9Hz),112.9(d,J=20.7Hz),109.1,56.6,41.3,39.1,20.4,5.5,3.6.

[0359] Example 2: Synthetic N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclopropanamine(S2): [ka] Step 1: N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclopropanamine fumarate (S2 fumarate) Cyclopropylamine (0.13 mL, 1.81 mmol) was added to a solution of 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol) in DMF (5 mL). This solution was heated to 80°C in a pressure tube for 4 hours. The reaction mixture was then cooled, poured into H2O (50 mL), and extracted with RINKAN (3 × 20 mL). The combined organic compounds were sequentially washed with H2O (3 × 100 mL) and brine (1 × 100 mL), dried, filtered, and concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain the title compound as a colorless oil, which was then formulated as a fumarate salt as a white crystalline solid according to general procedure F (115 mg, 39%). LCMS (condition A):t R(3.162 minutes) m / z=220.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.56(s,1H),8.16(dd,J=2.6,1.8Hz,1H),7.88(dd,J=9.6,2.7Hz,1H),7.42(d,J=2.4Hz,1H ),6.54(s,3H),3.11-2.98(m,2H),2.96-2.81(m,2H),2.46-2.36(m,1H),0.62-0.44(m,4H).

[0360] Example 5: Synthesis of N-cyclopropyl-N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclopropanamine (S5): [ka] Step 1: N-Cyclopropyl-N-(2-(5-Fluoro-1H-Pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclopropanamine hydrochloride (S5·HCl) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), N-cyclopropylcyclopropanamine hydrochloride (143 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol), and iPr2NEt (0.43 mL, 2.46 mmol). During purification, the title compound was produced as a colorless oil, and then formulated as a white crystalline solid (85 mg, 35%) as the hydrochloride salt according to general procedure E. LCMS (Condition A): t R (3.504 minutes) m / z=260.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.72(s,1H),10.89(s,1H),8.30-8.12(m,1H),8.01(dd,J=9.5,2.7Hz,1H),7.53(d,J=2.3Hz,1H ),3.54-3.39(m,2H),3.34-3.23(m,2H),3.10-2.97(m,2H),1.30-1.13(m,4H),0.94-0.75(m,4H); 13C NMR(101MHz,DMSO-d6):δ 154.7(d,J=238.7Hz),145.3,130.8(d,J=29.1Hz),126.6,119.1(d,J=6.8 Hz),112.5(d,J=20.7Hz),108.9(d,J=4.4Hz),56.5,38.1,19.8,3.4,3.2.

[0361] Example 6: Synthetic 5-fluoro-3-(2-(pyrroridine-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine(S6): [ka] Step 1: 5-Fluoro-3-(2-(pyrroridine-1-yl)ethyl)-1H-pyrroro[2,3-b]pyridine fumarate (S6 fumarate) Pyrrolidine (0.15 mL, 1.81 mmol) was added to a solution of 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol) in DMF (5 mL). This solution was heated to 80°C in a pressure tube for 4 hours. The reaction mixture was then cooled, poured into H2O (50 mL), and extracted with RINKAN (3 × 20 mL). The combined organic compounds were sequentially washed with H2O (3 × 100 mL) and brine (1 × 100 mL), dried, filtered, and concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain the title compound as a colorless oil, which was then formulated as a fumarate salt as a white crystalline solid according to general procedure F (120 mg, 53%). LCMS (condition A):t R (3.114 minutes) m / z=234.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.59(s,1H),8.18(dd,J=2.8,1.7Hz,1H),7.93(dd,J=9.7,2.8Hz,1H),7.44(d,J= 2.5Hz, 1H), 6.53 (s, 2H), 3.11-3.05 (m, 2H), 3.05-2.93 (m, 6H), 1.88-1.80 (m, 4H).

[0362] Example 7: Synthetic 5-fluoro-3-(2-(piperidine-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine(S7): [ka] Step 1: 5-Fluoro-3-(2-(piperidine-1-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine fumarate (S7 fumarate) Piperidine (0.18 mL, 2.2 equivalents, 1.81 mmol) was added to a solution of 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol) in DMF (5 mL). This solution was heated to 80°C in a pressure tube for 4 hours. The reaction mixture was then cooled, poured into H2O (50 mL), and extracted with RINKAN (3 × 20 mL). The combined organic compounds were sequentially washed with H2O (3 × 100 mL) and brine (1 × 100 mL), dried, filtered, and the filtrate was concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain the title compound as a colorless oil, which was then formulated as a fumarate salt as a white crystalline solid according to general procedure F (110 mg, 37%). LCMS (condition A):t R (3.315 minutes) m / z=248.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.56(s,1H),8.17(dd,J=2.8,1.7Hz,1H),7.90(dd,J=9.7,2.8Hz,1H),7.42(d,J=2.5Hz ,1H),6.55(s,2H),2.98-2.81(m,4H),2.77(m,4H),1.68-1.60(m,4H),1.49-1.46(m,2H).

[0363] Example 8: Synthesis of 3-(2-(1-azaspiro[3,3]heptan-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(S8): [ka] Step 1: 3-(2-(1-azaspiro[3,3]heptan-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine hydrochloride (S8·HCl) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), 1-azaspiro[3.3]heptane hydrochloride (143 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol), and iPr2NEt (0.43 mL, 2.46 mmol). During purification, the title compound was produced as a pale yellow oil, and then formulated as a brown solid (109 mg, 45%) hydrochloride according to general procedure E. LCMS (Condition A): t R (3.493 minutes) m / z=260.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.70(s,1H),10.71(s,1H),8.20(dd,J=2.8,1.7Hz,1H),8.06-7.98(m,1H),7.51(d,J=2.5Hz,1H),3.97-3.70(m,2H),3.50-3.4 1(m,1H),3.25-3.11(m,1H),3.03-2.91(m,2H),2.66(q,J=10.5Hz,1H),2.61-2.45(m,3H),2.18-2.06(m,2H),1.84-1.66(m,2H).

[0364] Example 9: Synthesis of 3-(2-(azetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(S9): [ka] Step 1: 3-(2-(azetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(S9) The title compound was synthesized using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.5 g, 2.06 mmol) and azetidine (0.69 mL, 10.3 mmol) according to general procedure C, but MeCN was used as the solvent instead of DMF. During purification, the title compound was a yellow solid (230 mg, 44%). 1 H NMR(400MHz,DMSO-d6):δ 11.45(s,1H),8.19-8.05(m,1H),7.81(dd,J=9.7,2.8Hz,1H),7.43-7.25 (m,1H),3.08(t,J=6.9Hz,4H),2.67-2.54(m,4H),1.93(p,J=6.9Hz,2H).

[0365] Step 2: 3-(2-(azetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine fumarate (S9 fumarate) 3-(2-(azetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (430 mg, 1.96 mmol) was isolated as an off-white solid and formulated as fumarate (540 mg, 82%) according to general procedure F. LCMS (Condition A): t R (2.999 minutes) m / z=220.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.59(s,1H),8.20-8.08(m,1H),7.92(dd,J=9.7,2.7Hz,1H),7.41(d,J=2.4Hz,1H),6.53( s,2H),3.69(t,J=7.7Hz,4H),3.14-3.04(m,2H),2.85-2.74(m,2H),2.18(p,J=7.7Hz,2H); 13 C NMR(101MHz,DMSO-d6):δ 167.6,154.8(d,J=238.3Hz),145.5,134.9,130.6(d,J=28.9Hz),126.4, 119.2(d,J=6.8Hz),112.4(d,J=20.6Hz),109.6,55.8,53.5,21.2,16.4; 1 H qNMR purity: 99.2% (ERETIC).

[0366] Example 11: Synthetic N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclobutanamine (S11): [ka] Step 1: N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclobutanamine maleate (S11 maleate) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), cyclobutylamine hydrochloride (115 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol), and iPr2NEt (0.43 mL, 2.46 mmol). During purification, the title compound was produced as a colorless oil, and then formulated as a white crystalline solid as maleate (75 mg, 25%) according to general procedure F. LCMS (condition A): t R (3.337 minutes) m / z=234.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.69(s,1H),8.54(s,1H),8.33-8.12(m,1H),7.91(dd,J=9.6,2.8Hz,1H),7.48(d,J=2.5Hz,1H),6.02(s,2H) ),3.73(p,J=8.0Hz,1H),3.09(t,J=7.4Hz,2H),2.97(t,J=7.5Hz,2H),2.27-2.01(m,4H),1.86-1.68(m,2H); 13 C NMR(101MHz,DMSO-d6):δ 167.2,154.8(d,J=238.5Hz),145.5,136.1,130.8(d,J=28.9Hz),126.9,119.1(d, J=6.8Hz),112.3(d,J=20.7Hz),108.4(d,J=4.4Hz),50.8,44.3,26.0,21.8,14.5.

[0367] Example 12: Synthesis of N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylcyclobutanamine (S12): [ka] Step 1: N-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)-N-methylcyclobutanamine hydrochloride (S12·HCl) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), N-methylcyclobutanamine hydrochloride (130 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol), and iPr2NEt (0.43 mL, 2.46 mmol). During purification, the title compound was produced as a colorless solid, and then formulated as a brown solid (192 mg, 73%) hydrochloride according to general procedure E. LCMS (Condition A): t R (3.895 minutes) m / z=300.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.71(s,1H),11.07(s,1H),8.31-8.13(m,1H),8.03(dd,J=9.6,2.7Hz,1H),7.51(d,J=2.5Hz,1H),3.78-3.6 0(m,1H),3.30-2.96(m,4H),2.69(d,J=5.0Hz,3H),2.46-2.27(m,2H),2.27-2.07(m,2H),1.82-1.53(m,2H); 13 C NMR(101MHz,DMSO-d6):δ 154.8(d,J=238.8Hz),145.3,130.8(d,J=29.0Hz),126.7,119.2(d,J=7.3Hz),11 2.6(d,J=21.3Hz),108.7(d,J=4.4Hz),58.5,52.0,35.6,25.5,25.1,19.6,13.0.

[0368] Example 15: Synthesis of 4-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)morpholine (S15): [ka] Step 1: 4-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)morpholine (S15) The title compound was synthesized using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), morpholine (0.21 mL, 2.47 mmol), and NaI (123 mg, 0.82 mmol) according to general procedure C. During purification, the title compound was produced as a white solid (180 mg, 88%). LC-MS (condition A): t R (2.954 minutes) m / z=250.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.48(s,1H),8.20-8.10(m,1H),7.84(dd,J=9.7,2.7Hz,1H),7.39(s,1H) ),3.64-3.53(m,4H),2.87-2.77(m,2H),2.60-2.52(m,2H),2.44(s,4H); 13 C NMR(101MHz,DMSO-d6):δ 154.7(d,J=238.1Hz),145.4,130.3(d,J=28.9Hz),125.8,119.6(d,J=6.7Hz),112.3(d,J=20.5Hz),112.0(d,J=4.3Hz),66.3,58.8,53.3,22.0.

[0369] Example 16: Synthesis of 3-(2-(2-methylazetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (S16): [ka] Step 1: 3-(2-(2-methylazetidine-1-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine hydrochloride (S16·HCl) The title compound was synthesized according to general procedure D using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), 2-methylazetidine hydrochloride (115 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol), and iPr2NEt (0.43 mL, 2.46 mmol). During purification, the title compound was produced as a pale yellow oil, and then formulated as an off-white solid (94 mg, 42%) hydrochloride according to general procedure E. LCMS (Condition A): t R (3.127 minutes) m / z=234.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.70(s,1H),10.88(s,1H),8.20(dd,J=2.5,1.8Hz,1H),8.04(dd,J=9.6,2.6Hz,1H),7.48(d,J=2.5Hz,1H),4.54-4.33(m, 1H),3.95-3.68(m,2H),3.55-3.20(m,2H),3.07-2.88(m,2H),2.45-2.29(m,1H),2.23-2.03(m,1H),1.51(d,J=6.6Hz,3H).

[0370] Example 17: Synthesis of N-(cyclopropylmethyl)-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (S17): [ka] Step 1: N-(cyclopropylmethyl)-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine(S17) The title compound was synthesized using 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.2 g, 0.82 mmol), N-(cyclopropylmethyl)amine (0.21 mL, 2.47 mmol), and NaI (123 mg, 0.82 mmol) according to general procedure C. During purification, the title compound was produced as a pale yellow oil (150 mg, 78%). 1H NMR(400MHz,DMSO-d6):δ 11.48(s,1H),8.14(dd,J=2.7,1.7Hz,1H),7.83(dd,J=9.7,2.7Hz,1H),7.36(s,1H),2.84-2 .73(m,4H),2.40(d,J=6.6Hz,2H),0.95-0.77(m,1H),0.45-0.29(m,2H),0.13--0.02(m,2H); 13 C NMR(101MHz,DMSO-d6):δ 154.7(d,J=238.1Hz),145.5,130.3(d,J=28.9Hz),125.8,119.6(d,J=6.6 Hz),112.3(d,J=18.2Hz),112.2(d,J=2.1Hz),54.0,49.8,25.5,11.2,3.2.

[0371] Step 2: N-(cyclopropylmethyl)-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine hydrochloride (S17·HCl) N-(cyclopropylmethyl)-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (140 mg, 0.60 mmol) was formulated as an off-white solid hydrochloride salt according to general procedure E (77 mg, 48%). LCMS (Condition A): t R (3.348 minutes) m / z=234.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.73(s,1H),9.21(s,2H),8.24-8.16(m,1H),8.04(dd,J=9.6,2.7Hz,1H),7.49(d,J=2.5Hz,1H) ,3.22-2.96(m,4H),2.84-2.74(m,2H),1.21-0.99(m,1H),0.66-0.47(m,2H),0.46-0.29(m,2H). 13C NMR(101MHz,DMSO-d6):δ 154.7(d,J=238.5Hz),145.2,130.5(d,J=29.2Hz),126.8,119.4(d,J=6.8Hz ),112.8(d,J=20.8Hz),109.0(d,J=4.3Hz),51.1,46.5,41.9,21.6,7.0,4.0. 1 H qNMR purity: 92.9% (ERETIC).

[0372] Example 25: Synthesis of 3-(2-(2-azabicyclo[3.1.0]hexane-2-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(S25): [ka] Step 1: 3-(2-(2-azabicyclo[3.1.0]hexane-2-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine(S25) A solution of 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (250 mg, 1.03 mmol) in acetonitrile (5 mL) was treated with 2-azabicyclo[3.1.0]hexane hydrochloride (246 mg, 2.06 mmol) and iPr2NEt (0.9 mL, 5.14 mmol), and the reaction mixture was stirred at room temperature for 48 hours. The reaction mixture was diluted with a semi-saturated aqueous NH4Cl solution (100 mL), and then extracted with CH2Cl2 (25 mL × 3), followed by iPrOH:CHCl3 (1:3, 25 mL × 3). The combined organic layer was concentrated, and the residue was purified by flash chromatography (1% to 8% MeOH / NH3 in CH2Cl2) to obtain the title compound (210 mg, 83%) as an off-white solid. 1H NMR(400MHz,CDCl3):δ 9.43(s,1H),8.20-8.01(m,1H),7.63(ddd,J=8.9,2.8,0.6Hz,1H),7.24(d,J=2.3Hz,1H),3.16-2.95(m,3H),2.94-2.79(m,3H),2 .15-1.94(m,2H),1.90(dd,J=11.4,6.9Hz,1H),1.58-1.47(m,1H),0.71(ddd,J=6.6,4.3,2.7Hz,1H),0.20(dt,J=8.1,5.9Hz,1H); 13 C NMR(101MHz,CDCl3):δ 155.6(d,J=241.4Hz),145.7,131.6(d,J=29.5Hz),124.5,120.2(d,J=6.3 Hz),113.1,113.0(d,J=20.5Hz),55.1,48.8,40.7,26.8,25.1,15.4,2.0.

[0373] Step 2: 3-(2-(2-azabicyclo[3.1.0]hexane-2-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine fumarate (S25 fumarate) 3-(2-(2-azabicyclo[3.1.0]hexane-2-yl)ethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (185 mg, 0.75 mmol) was formulated as a white solid fumarate (162 mg, 59%) according to general procedure F. LCMS (Condition A): t R (3.216 minutes) m / z=246.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.55(s,1H),8.16(dd,J=2.6,1.8Hz,1H),7.88(dd,J=9.7,2.7Hz,1H),7 .43(d,J=2.5Hz,1H),6.57(s,2H),3.23-3.07(m,1H),3.02(td,J=6.0,2.6 Hz,1H),2.99-2.88(m,4H),2.32-2.17(m,1H),2.01-1.77(m,2H),1.57-1. 44(m,1H),0.85(ddd,J=6.5,4.5,2.6Hz,1H),0.30(dt,J=8.1,6.1Hz,1H);13 C NMR(101MHz,DMSO-d6):δ 167.1,154.7(d,J=238.3Hz),145.5,134.6,130.5(d,J=28.9Hz),126.1,119.4(d,J=6. 8Hz),112.4(d,J=20.5Hz),110.8(d,J=4.4Hz),53.8,47.8,40.0,25.8,23.3,14.9,2.2; 1 H qNMR purity: 100% (ERETIC).

[0374] Example 30: Synthesis of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-fluorobenzyl)ethane-1-amine (S30). [ka] Step 1: 2-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)isoindoline-1,3-dione(66). Potassium phthalimide (1.01 g, 4.95 mmol) was added to a solution of 3-(2-bromoethyl)-5-fluoro-1H-pyrrolo[2,3-b]pyridine (0.8 g, 3.29 mmol) in DMF (5 mL). This solution was heated to 80°C in a pressure tube for 4 hours. The reaction mixture was then cooled, poured into H₂O (50 mL), and extracted with ELISA (3 × 20 mL). The combined organic compounds were sequentially washed with H₂O (3 × 100 mL) and brine (1 × 100 mL), dried, and concentrated under reduced pressure in MgSO₄. The resulting oil was purified by column chromatography (10% MeOH / CH₂Cl₂) to obtain the desired compound as a yellow solid.

[0375] Step 2: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (S29). To a solution of 2-(2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)isoindoline-1,3-dione (800 mg, 2.59 mmol) in EtOH (10 mL), hydrazine monohydrate (1.25 mL, 25.9 mmol) was added, and the resulting mixture was refluxed for 16 hours. The cooled reaction mixture was filtered, and the filtrate was concentrated under vacuum. The residue was purified by flash chromatography (5-20% MeOH in CH2Cl2) to obtain the title compound. 1 H NMR (400MHz, DMSO-d6): δ 8.19-8.06(m,1H),7.83(dd,J=9.7,2.8Hz,1H),7.35(s,1H),3.17(s,2H),2.85-2.76(m,2H),2.76-2.64(m,2H).

[0376] Step 3: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-fluorobenzyl)ethane-1-amine(S30). To a stirred solution of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (160 mg, 0.89 mmol) in MeOH (10 mL) at 0°C, NaCNBH3 (56 mg, 0.89 mmol) was added dropwise, followed by a solution of 2-fluorobenzaldehyde (111 mg, 0.89 mmol) in MeOH (5.0 mL). The mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 M NaOH (4.0 mL), and volatiles were removed under a stream of nitrogen gas. The remaining aqueous phase was extracted with RINKAN (3 × 10 mL), the combined organic matter was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-fluorobenzyl)ethane-1-amine (127 mg, 50%) as a clear yellow viscous oil. 1H NMR(400MHz,CDCl3):δ 9.05(br s,1H),8.16-8.15(m,1H),7.55(ddd,J=8.9,2.7,0.7Hz,1H),7.31-7.26(m,1H),7.25-7.18(m,2H) ,7.08(td,J=7.5,1.2Hz,1H),7.00(ddd,J=10.3,8.1,1.2Hz,1H),3.88(s,2H),3.00-2.88(m,4H).

[0377] Step 4: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-fluorobenzyl)ethane-1-amine fumarate (S30 fumarate). 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-fluorobenzyl)ethane-1-amine (122 mg, 0.43 mmol) was isolated as off-white crystals and formulated as fumarate (92 mg, 51%) according to general procedure F. LCMS (Condition A): t R (3.770 minutes) m / z=288.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.56(br s,1H),8.16(dd,J=2.7,1.7Hz,1H),7.52(td,J=7.5,1.8Hz,1H),7.41(d,J=2.5Hz,1H ),7.40-7.33(m,1H),7.25-7.15(m,2H),6.56(s,2H),4.00(s,2H),3.05-2.89(m,4H).

[0378] Example 31: Synthesis of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-fluorobenzyl)ethane-1-amine (S31). [ka] Step 1: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-fluorobenzyl)ethane-1-amine(S31). To a stirred solution of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (160 mg, 0.89 mmol) in MeOH (10 mL) at 0°C, NaCNBH3 (56 mg, 0.89 mmol) was added dropwise, followed by a solution of 3-fluorobenzaldehyde (111 mg, 0.89 mmol) in MeOH (5.0 mL). The mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 M NaOH (4.0 mL), and volatiles were removed under a stream of nitrogen gas. The remaining aqueous phase was extracted with RINKAN (3 × 10 mL), the combined organic matter was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-fluorobenzyl)ethane-1-amine (61 mg, 24%) as a clear yellow viscous oil. 1 H NMR(400MHz,CDCl3):δ 8.99(br s,1H),8.20-8.15(m,1H),7.58(ddd,J=9.0,2.7,0.7Hz,1H),7.28-7.22(m,2H),7.21( d,J=2.4Hz,1H),7.07-6.97(m,2H),6.96-6.89(m,1H),3.81(s,2H),2.98-2.89(m,4H).

[0379] Step 2: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-fluorobenzyl)ethane-1-amine fumarate (S31 fumarate). 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-fluorobenzyl)ethane-1-amine (56 mg, 0.20 mmol) was isolated as off-white crystals and formulated as fumarate (55 mg, 70%) according to general procedure F. LCMS (Condition A): t R (3.856 minutes) m / z=288.10[M+H] + ; 1H NMR(400MHz,DMSO-d6):δ 11.56(br s,1H),8.16(dd,J=2.8,1.7Hz,1H),7.84(dd,J=9.6,2.8Hz,1H),7.44-7.34(m,2H), 7.30-7.21(m,2H),7.17-7.08(m,1H),6.53(s,2H),3.97(s,3H),3.01-2.88(m,4H).

[0380] Example 32: Synthesis of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-methoxybenzyl)ethane-1-amine (S32). [ka] Step 1: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-methoxybenzyl)ethane-1-amine(S32). To a stirred solution of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (160 mg, 0.89 mmol) in MeOH (10 mL) at 0°C, NaCNBH3 (56 mg, 0.89 mmol) was added dropwise, followed by a solution of 2-methoxybenzaldehyde (122 mg, 0.89 mmol) in MeOH (5.0 mL). The mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 M NaOH (4.0 mL), and volatiles were removed under a stream of nitrogen gas. The remaining aqueous phase was extracted with RINKAN (3 × 10 mL), the combined organic matter was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-methoxybenzyl)ethane-1-amine (134 mg, 50%) as a yellow viscous oil. 1H NMR(400MHz,CDCl3):δ 9.07(br s,1H),8.13-8.08(m,1H),7.49(dd,J=9.0,2.7Hz,1H),7.26-7.17(m,3H),6.90(td,J =7.4,1.1Hz,1H),6.77(dd,J=8.1,1.1Hz,1H),3.86(s,2H),3.63(s,3H),2.95(s,4H).

[0381] Step 2: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-methoxybenzyl)ethane-1-amine fumarate (S32 fumarate). 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(2-methoxybenzyl)ethane-1-amine (129 mg, 0.43 mmol) was isolated as white crystals and formulated as fumarate (107 mg, 60%) according to general procedure F. LCMS (Condition A): t R (3.907 minutes) m / z=300.15[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.63-11.58(m,1H),8.17(t,J=2.2Hz,1H),7.85(dd,J=9.6,2.8Hz,1H),7.42(d,J=2.4Hz,1H),7.37(dd,J=7.5,1.7Hz,1H),7.32(t d,J=7.8,1.7Hz,1H),7.00(d,J=8.2Hz,1H),6.94(td,J=7.4,1.0Hz,1H),6.51(s,2H),3.98(s,2H),3.75(s,3H),3.07-2.92(m,4H).

[0382] Example 33: Synthesis of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-methoxybenzyl)ethane-1-amine (S33): [ka] Step 1: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-methoxybenzyl)ethane-1-amine(S33). To a stirred solution of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (128 mg, 0.71 mmol) in MeOH (10 mL) at 0°C, NaCNBH3 (45 mg, 0.71 mmol) was added dropwise, followed by a solution of 3-methoxybenzaldehyde (97 mg, 0.71 mmol) in MeOH (5.0 mL). The mixture was stirred at room temperature for 2 hours. The reaction was quenched with 2 M NaOH (4.0 mL), and volatiles were removed under a stream of nitrogen gas. The remaining aqueous phase was extracted with RINKAN (3 × 10 mL), the combined organic matter was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-methoxybenzyl)ethane-1-amine (46 mg, 21%) as a clear viscous oil. 1 H NMR(400MHz,CDCl3):δ 9.01(br s,1H),8.10(t,J=2.2Hz,1H),7.55(dd,J=8.9,2.7Hz,1H),7.25-7.18(m,2H),6. 89-6.85(m,2H),6.82-6.77(m,1H),3.84(s,2H),3.78(s,3H),3.03-2.91(m,4H).

[0383] Step 2: 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-methoxybenzyl)ethane-1-amine maleate (S33·maleate). 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)-N-(3-methoxybenzyl)ethane-1-amine (46 mg, 0.15 mmol) was isolated as a white crystal and formulated as maleate (37 mg, 58%) according to general procedure F. LCMS (Condition A): t R (3.895 minutes) m / z=300.15[M+H] + ; 1H NMR(400MHz,DMSO-d6):δ 11.68(s,1H),8.77(br s,1H),8.20(dd,J=2.8,1.7Hz,1H),7.87(dd,J=9.6,2.7Hz,1H),7.48(d,J=2.5Hz,1H),7.41-7.32(m,1H),7.10-7.07(m,1H),7. 06-7.03(m,1H),7.00(ddd,J=8.4,2.6,0.9Hz,1H),6.02(s,2H),4.17(s,2H),3.77(s,3H),3.25-3.17(m,2H),3.08-2.99(m,2H).

[0384] Example 34: Synthesis of N-benzyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (S34). [ka] Step 1: N-benzyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (S34). To a stirred solution of 2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (128 mg, 0.71 mmol) in MeOH (10 mL) at 0°C, NaCNBH3 (45 mg, 0.71 mmol) was added dropwise, followed by a solution of benzaldehyde (76 mg, 0.71 mmol) in MeOH (5.0 mL). The mixture was stirred at room temperature for 2 hours. The reaction was quenched with 2 M NaOH (4.0 mL), and volatiles were removed under a stream of nitrogen gas. The remaining aqueous phase was extracted with RINKAN (3 × 10 mL), the combined organic matter was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (1-10% MeOH / NH3 in CH2Cl2) to obtain N-benzyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (72 mg, 37%) as a slightly yellowish viscous oil, which was allowed to solidify overnight. 1H NMR(400MHz,CDCl3):δ 9.01(br s,1H), 8.16(t,J=2.2Hz,1H),7.57(dd,J=9.0,2.7Hz,1H),7.33-7.22(m,5H),7.19(d,J=2.3Hz,1H),3.83(s,2H),3.01-2.88(m,4H).

[0385] Step 2: N-benzyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine fumarate (S34 fumarate). N-benzyl-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-amine (68 mg, 0.25 mmol) was isolated as a white crystal and formulated as fumarate (66 mg, 68%) according to general procedure F. LCMS (Condition A): t R (3.776 minutes) m / z=270.10[M+H] + ; 1 H NMR(400MHz,DMSO-d6):δ 11.58(s,1H),8.16(dd,J=2.8,1.7Hz,1H),7.45-7.40(m,3H),7.39-7.29(m,3H),6.52(s,2H),3.99(s,2H),3.05-2.91(m,4H).

[0386] Example 41: Synthesis of N-methyl-N-(2-(5-(trifluoromethoxy)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethyl)cyclopropanamine (S41). [ka] Step 1: 5-(trifluoromethoxy)pyridine-2-amine (68) To a solution of 2-chloro-5-(trifluoromethoxy)pyridine (10.0 g, 50.6 mmol), diphenylmethanimine (11.0 g, 60.8 mmol, 10.2 mL), and t-BuOK (11.4 g, 101 mmol) in toluene (70 mL), DPEPhos (1.09 g, 2.02 mmol) and Pd2(dba)3 (927 mg, 1.01 mmol, 0.02 eq) were added, and the mixture was stirred at 80°C for 2 hours. The mixture was filtered, and the filter cake was washed with ELISA (20 mL). The filtrate was treated with 3 M aqueous HCl (800 mL) and stirred at 50°C for 1 hour. The reaction mixture was cooled to room temperature, and the phases were separated. The aqueous phase was adjusted to pH 9 with aqueous NaOH and extracted with ELISA (2 × 10 mL). The combined organic matter was dried on anhydrous Na2SO4 and concentrated under reduced pressure to obtain crude 5-(trifluoromethoxy)pyridine-2-amine (10.0 g) as a brown oil.

[0387] Step 2: 3-Bromo-5-(trifluoromethoxy)pyridine-2-amine (69) To a solution of 5-(trifluoromethoxy)pyridine-2-amine (9.00 g, 50.5 mmol) in CH2Cl2 (63 mL), NBS (8.99 g, 50.5 mmol) was added, and the mixture was stirred at 25°C for 10 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / Â100:1~0:1) to obtain 3-bromo-5-(trifluoromethoxy)pyridine-2-amine (1.20 g, 9%) as a yellow solid. 1 H NMR (400MHz CDCl3): δ 8.00 (d, J = 2.0 Hz, 1H), 7.62 (d, J = 1.7 Hz, 1H), 5.27-4.84 (m, 2H).

[0388] Step 3: 5-(trifluoromethoxy)-3-((trimethylsilyl)ethynyl)pyridine-2-amine(70) To a solution of 3-bromo-5-(trifluoromethoxy)pyridine-2-amine (1.00 g, 3.89 mmol), ethinyltrimethylsilane (1.15 g, 11.7 mmol, 1.62 mL), and Et3N (1.18 g, 11.7 mmol, 1.62 mL) in DMF (5.0 mL), CuI (74.1 mg, 0.39 mmol) and Pd(PPh3)2Cl2 (137 mg, 0.20 mmol) were added, and the mixture was stirred under a nitrogen atmosphere at 105°C for 6 hours. The reaction mixture was filtered, and the filter cake was washed with  (20 mL). The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (petroleum ether / Â100:1~0:1) to obtain crude 5-(trifluoromethoxy)-3-((trimethylsilyl)ethynyl)pyridine-2-amine (1.00 g) as a brown solid. 1 H NMR (400MHz CDCl3): δ 7.96 (d, J = 2.4 Hz, 1H), 7.46-7.41 (m, 1H), 5.13 (br s, 2H), 0.31-0.26 (m, 9H).

[0389] Step 4: 5-(trifluoromethoxy)-1H-pyrrolo[2,3-b]pyridine (71) To a solution of 5-(trifluoromethoxy)-3-((trimethylsilyl)ethynyl)pyridine-2-amine (1.00 g, 3.65 mmol) in NMP (7.0 mL), t-BuOK (2.05 g, 18.2 mmol) was added, and the mixture was stirred at 130 °C for 4 hours. The reaction mixture was poured into H₂O (20 mL) and then extracted with  (3 × 10 mL). The combined organic matter was washed with brine (10 mL), dried on anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / Â-80:1~0:1) to obtain 5-(trifluoromethoxy)-1H-pyrrolo[2,3-b]pyridine (500 mg, 68%) as a pale yellow solid. 1 H NMR: (400MHz CDCl3): δ 10.1-9.67(m,1H),8.29(d,J=1.9Hz,1H),7.86(s,1H),7.52-7.40(m,1H),6.57(dd,J=1.90,3.5Hz,1H).

[0390] Step 5: 2-Chloro-1-(5-(trifluoromethoxy)-1H-pyrrolo[2,3-b]pyridine-3-yl)ethane-1-one(72) To a solution of 5-(trifluoromethoxy)-1H-pyrrolo[2,3-b]pyridine (300 mg, 1.48 mmol) in CH2Cl2 (10 mL), AlCl3 (989 mg, 7.42 mmol, 406 μL) was added under a nitrogen atmosphere at 0°C. The mixture was stirred at 0°C for 30 minutes, and then 2-chloroacetyl chloride (503 mg, 4.45 mmol, 355 μL) was added dropwise. The reaction mixture was stirred at 50°C for 10 hours, and then quenched with H2O (50 mL). The mixture was ...

Claims

1. Equation (I): 【Chemistry 1】 A compound of, During the ceremony, R １ is independently hydrogen, C １～６ alkyl, C １～６ haloalkyl, C ２～６ alkenyl, C ２～６ haloalkenyl, C ２～６ alkynyl, C ２～６ haloalkynyl, C ３～８ cycloalkyl, C ４～１４ alkylenecycloalkyl, C ３ -C ８ heterocycloalkyl, C ４ -C １４ alkylenheterocycloalkyl, C ６～１２ aryl, C ７～１８ alkylenearyl, C ５～１０ heteroaryl, and C ６～１６ is selected from alkyleneheteroaryl, Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryls, halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ , and SO ２ R ４ Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryl, (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring heteroparts selected from ３～６ Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R ２ However, independently, hydrogen, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Selected from alkylene heteroaryls, Said C １～６ haloalkyl, C ３～８ cycloalkyl, C ４～１４ alkylenecycloalkyl, C ３ -C ８ heterocycloalkyl, C ４ -C １４ alkylenheterocycloalkyl, C ６～１２ aryl, C ７～１８ alkylenearyl, C ５～１０ heteroaryl, and C ６～１６ alkylenheteroaryl are each optionally substituted with one or more substituents independently selected from halogen, CN, C １～８ alkoxy, C １～８ alkylamino, C １～８ alkylsulfonyl, CO ２ R ４ , C(O)N(R ４ ), ２ , OR ４ , N(R ４ ), ２ , NO ２ , SR ４ , and SO ２ R ４ and are each optionally substituted with one or more substituents independently selected therefrom, Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryl, (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring heteroparts selected from ３～６ Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Alternatively, R １ and R ２ However, together with the atoms to which these are bonded, they form O, S, S(O), SO ２ , N, and NR ４ C comprising 0, 1, or 2 additional ring heteroparts selected from ３～８ Forms heterocycloalkyl groups, Said C ３～８ Heterocycloalkyl groups include halogens, (O), CN, and C. １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ SO ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ , and NR ４ C containing one or two ring heteroparts selected from ３～６ It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. R ３ However, hydrogen, C １～６ Alkyl, C ３～８ Cycloalkyl, or C ４～１４ Selected from alkylene cycloalkyl, Alternatively, R ３ , and R １ and R ２ One of them combines with the atom to which they are bonded, C ３～１２ Forms heterocycloalkyl groups, Said C ３～１２ Heterocycloalkyl groups include halogens, (O), CN, and C. １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ SO ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ , and NR ４ C containing one or two ring heteroparts selected from ３～６ It is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R ４ However, independently, hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, as well as O, S, S(O), SO ２ , N, and NR ５ C containing one or two ring heteroparts selected from ３～７ Selected from heterocycloalkyl groups, Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, and C ３～７ Heterocycloalkyls are halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ５ , C(O)N(R ５ ) ２ , OR ５ , N(R ５ ) ２ NO ２ , SR ５ , and SO ２ R ５ Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. Said C ３ ~C ７ Cycloalkyl and C ３～７ Heterocycloalkyl groups are (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, and NR ５ C containing one or two ring heteroparts selected from ３～６ Each of the substituents is further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. Each R ５ However, independently, hydrogen, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Selected from heteroaryls, Said C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryls are halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ C(O)NH ２ , C(O)N(CH ３ ) ２ C(O)NHCH ３ OH, NH ２ , N (CH ３ ) ２ , NHCH ３ NO ２ SH, SCH ３ SO ２ CH ３ EN SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH, and NCH ３ C containing one or two ring heteroparts selected from ３～６ Each of the substituents is optionally substituted with one or more substituents independently selected from the heterocycloalkyl group. R ７ , R ８ , R ９ , R １０ , and R １１ However, each independently, hydrogen, halogen, CN, OR １３ , N(R １３ ) ２ , SR １３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２ ~C ６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C １～６ Alkylamine, C １～６ Alkoxy, C １～６ Haloalkoxy, CO ２ R １３ , C(O)R １３ , C(O)N(R １３ ) ２ , C(O)C(O)N(R １３ ) ２ OC(O)R １３ , OC(O)OR １３ ,OC(O)N(R １３ ) ２ OS(O)R １３ OS(O)N(R) １３ ) ２ OSO ２ R １３ , OP(O)(OR １３ ) ２ , OC １～６ Alkylene P(O)(OR) １３ ) ２ S(O)R １３ , S(O)N(R １３ ) ２ SO ２ R １３ , N(R １３ ) ２ , N(R １３ ) C(O)R １３ , N(R １３ ) C(O)OR １３ , N(R １３ ) C(O)N(R １３ ) ２ NO ２ , C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryl, C ４～１６ Selected from alkylene heteroaryls, Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２ ~C ６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C １～６ Alkylamine, C １～６ Alkoxy, C １～６ Haloalkoxy, C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ４～１６ Alkylene heteroaryls, halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １３ , C(O)N(R １３ ) ２ , OR １３ , N(R １３ ) ２ NO ２ , SR １３ , and SO ２ R １３ It is optionally substituted with one or more substituents independently selected from the original, Said C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ４～１６ Alkylene heteroaryl, (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, and NR １３ C containing one or two ring heteroparts selected from ３～６ Each of the substituents is further optionally substituted with one or more substituents selected from heterocycloalkyl groups. Each R １３ However, independently, hydrogen, C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Selected from alkylene heteroaryls, Said C １～６ Alkyl, C ２～６ Alkenil, C ２～６ Alkinyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryls, halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ C(O)NH ２ , C(O)N(CH ３ ) ２ C(O)NHCH ３ OH, NH ２ , N (CH ３ ) ２ , NHCH ３ NO ２ SH, SCH ３ SO ２ CH ３ EN SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring heteroparts selected from ３～６ Compounds, or pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs, or prodrugs thereof, each optionally substituted with one or more substituents independently selected from a heterocycloalkyl group.

2. R ９ However, independently, halogen, CN, -OH, C １～６ Haloalkyl, C １～６ Alkoxy, and C １～６ Selected from haloalkoxys, Said C １～６ Haloalkyl, C １～６ Alkoxy, C １～６ Haloalkoxys are halogens, CN, and C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １３ , C(O)N(R １３ ) ２ , OR １３ , N(R １３ ) ２ NO ２ , SR １３ , and SO ２ R １３ The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, which is optionally substituted with one or more substituents independently selected from the compound.

3. R ９ However, halo, CN, -OH, C １～４ Alkoxy, C １～４ Haloalkoxy and C １～４ A compound according to claim 2, selected from haloalkyls, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

4. R ９ The compound according to claim 3, selected from fluoro, chloro, bromo, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

5. R ７ However, H is R ８ However, H is R １０ However, H is present, and the compound is of formula (II): 【Chemistry 2】 A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, provided by [the relevant authority].

6. R １ However, independently, hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Selected from alkylene heteroaryls, Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryls, halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ , and SO ２ R ４ Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryl, (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring heteroparts selected from ３～６ A compound according to any one of claims 1 to 5, each further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

7. R １ However, independently, hydrogen, C １～６ Alkyl, C １～６ Selected from haloalkyls, Said C １～６ Alkyl, C １～６ Haloalkyls include halogens, CN, and C. １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ , and SO ２ R ４ A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, each optionally substituted with one or more substituents independently selected from the compound.

8. R ２ However, independently, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Selected from alkylene heteroaryls, Said C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryls, halogens, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ , and SO ２ R ４ Each substituent is optionally substituted with one or more substituents independently selected from the original molecule. Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkylene heterocycloalkyl, C ６～１２ Ariel, C ７～１８ Alkylenearyl, C ５～１０ Heteroaryls, and C ６～１６ Alkylene heteroaryl, (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring heteroparts selected from ３～６ A compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, each further optionally substituted with one or more substituents independently selected from the heterocycloalkyl group.

9. R １ and R ２ However, together with the atoms to which these are bonded, they form O, S, S(O), SO ２ , N, and NR ４ C comprising 0, 1, or 2 additional ring heteroparts selected from ３～８ Forms heterocycloalkyl groups, Said C ３～８ Heterocycloalkyl groups include halogens, (O), CN, and C. １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ NO ２ , SR ４ SO ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenil, C ２～６ Haloalkenil, C ２～６ Alkinyl, C ２～６ Haloalkynyl, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ , and NR ４ C containing one or two ring heteroparts selected from ３～６ A compound according to any one of claims 1 to 6, further optionally substituted with one or more substituents selected from heterocycloalkyl groups, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

10. R １ and R ２ But together they become O, S, S(O), SO ２ , N, and NR ４ C containing 0 or 1 additional ring heteroparts selected from ４～８ Form a heterocycloalkyl group, and the C ４～８ Heterocycloalkyls are halogens, C １～８ Alkoxy, C １～６ Alkyl, C １～６ Haloalkyl, C ３～６ Cycloalkyls, as well as O, S, N, S(O), SO ２ , and NR ４ C containing one or two ring heteroparts selected from ３～６ The compound according to claim 9, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, which is optionally substituted with one or more substituents selected from heterocycloalkyl groups.

11. R １ and R ２ However, together with the nitrogen atoms to which these are bonded, C does not contain any additional ring heteroparts. ４～８ A compound according to claim 9 or 10 that forms a heterocycloalkyl group, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

12. R １ and R ２ However, together with the nitrogen atom to which these are bonded, a bicyclic carbon atom is formed. ６～８ A compound according to any one of claims 9 to 11 that forms a heterocycloalkyl group, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

13. R １ However, independently, hydrogen, and optionally substituted C １～６ Alkyl, optionally substituted C １～６ Haloalkyl, optionally substituted C ３～８ Cycloalkyl, optionally substituted C ４～１４ Alkylenecycloalkyl, optionally substituted C ３ ~C ８ Heterocycloalkyl, optionally substituted C ４ ~C １４ Alkylene heterocycloalkyl, optionally substituted C ６～１２ Aaryl, optionally substituted C ７～１８ Alkylenearyl, optionally substituted C ５～１０ Heteroaryl and optionally substituted C ６～１６ Selected from alkylene heteroaryls, R ２ However, C is independently and arbitrarily substituted. ３～８ Cycloalkyl, optionally substituted C ４～１４ Alkylenecycloalkyl, optionally substituted C ３ ~C ８ Heterocycloalkyl, optionally substituted C ４ ~C １４ Alkylene heterocycloalkyl, optionally substituted C ６～１２ Aaryl, optionally substituted C ７～１８ Alkylenearyl, optionally substituted C ５～１０ Heteroaryl and optionally substituted C ６～１６ Selected from alkylene heteroaryls, Or, R １ and R ２ However, together with the atoms to which these are bonded, they form O, S, S(O), SO ２ , N, and NR ４ Optionally substituted C containing 0, 1, or 2 additional ring heteromologies selected from ３～８ A compound according to any one of claims 1 to 5 that forms a heterocycloalkyl group, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

14. R １ and R ２ However, together with the nitrogen to which these are bound, the following occurs: -NH ２ 、 【Transformation 3】 A compound according to any one of claims 1 to 5, which forms any one of the following, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

15. R ３ A compound according to any one of claims 1 to 13, wherein the compound is hydrogen, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

16. below: Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 A compound according to claim 1, selected from, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

17. A pharmaceutical product comprising a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

18. A pharmaceutical composition comprising a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, and a pharmaceutically acceptable excipient.

19. A method for treating a disease, disorder or condition by activation of serotonin receptors, the method comprising administering to a subject in need thereof a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, a pharmaceutical according to claim 17, or a pharmaceutical composition according to claim 18.

20. A method for treating mental illness, comprising administering to a subject in need thereof an effective amount of a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, a pharmaceutical product according to claim 17, or a pharmaceutical composition according to claim 18.

21. A method for treating a disease, disorder or condition of the central nervous system (CNS) and / or a disease, disorder or condition of the nervous system, comprising administering to a subject in need thereof an effective amount of a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, a pharmaceutical product according to claim 17, or a pharmaceutical composition according to claim 18.

22. A method for increasing neuronal plasticity and / or increasing dendritic spine density, comprising contacting nerve cells with a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, a pharmaceutical according to claim 17, or a pharmaceutical composition according to claim 18.

23. ● Treating diseases, disorders, or conditions by activating serotonin receptors, and / or ● Treating mental illness, and / or ● Diseases, disorders or conditions of the central nervous system (CNS), and / or treatment of diseases, disorders or conditions of the nervous system, and / or ● Use of a compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, in the preparation of a pharmaceutical for one or more of the purposes of increasing neural plasticity and / or increasing dendritic spine density.

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