Pyrrolopyridine compounds for treatment of mental disorders

Abstract

The present disclosure relates generally to compounds, methods for their synthesis and their use in the treatment of mental or central nervous system disorders.

Description

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

[0002] This disclosure generally relates to novel compounds, methods of their synthesis, and their use in the treatment of mental illnesses or central nervous system disorders. Background Technology

[0003] Mental illness encompasses many neuropsychiatric disorders that impose a tremendous burden on the lives of their patients. Diagnoses such as antidepressant disorder, major depressive disorder, eating disorders, substance abuse disorders, post-traumatic stress disorder, obsessive-compulsive disorder, attention deficit disorder, and schizophrenia can produce devastating symptoms, to the point that many patients lose the ability to lead normal lives.

[0004] A wide variety of serotonergic drugs, such as antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors, are commercially available for the treatment of mental illnesses. Unfortunately, in many indications, these treatments offer limited benefit compared to a placebo. Furthermore, these treatments can cause a variety 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 symptoms and a wide range of adjunctive medical indications. The development of new treatment options is limited by the availability of many of these drugs, and the pharmaceutical industry faces increasing financial pressures, leading to a complete neglect of neuroscience approaches. The need for more effective mental health treatments is increasingly unmet, and the global COVID-19 pandemic is likely to increase the disease burden worldwide.

[0005] In the 1950s and 1960s, the use of hallucinogenic drugs for the treatment of various mental illnesses was extensively explored, and these substances showed promise as treatments for many central nervous system (CNS) disorders. Decades after being banned, scientific research into the use of hallucinogens as treatments for mental illnesses is gaining momentum. The serotonergic hallucinogen psilocybin has been designated by the FDA as a breakthrough therapy for the treatment of major depressive disorder (2019) and antidepressant disorder (2018). Psilocybin is a prodrug compound produced by many species of mushrooms collectively known as psilocybin mushrooms or "magic mushrooms." Psilocybin is rapidly metabolized into the bioactive compound psilocin, which alters states of consciousness, including perceptual changes, visual hallucinations, and distortions of spatial, temporal, and self-perception. Many patients have reported psychic or "mystical" experiences that have profound and lasting effects on their mood and behavior. Psilocysteine ​​has shown promise in over 50 clinical trials for neuropsychiatric indications, including various anxiety disorders, obsessive-compulsive disorder, anorexia nervosa, alcohol dependence, and tobacco addiction. Psilocysteine, as well as... N , N -Dimethyltryptamine (DMT) and 5-methoxy- N,N Other hallucinogenic compounds, such as 5-MeO-DMT, have direct and lasting effects on mental states, which extend far beyond the duration of their effects. This is likely because these hallucinogenic compounds can stimulate increased neuroplasticity, promote neurogenesis, and increase the density of dendritic spines in synaptic neurons in the brain.

[0006] To date, psilocybin remains classified as a controlled substance of abuse and / or drug under national drug laws in most countries. However, recent clinical studies have brought increasing recognition of the potential of hallucinogenic drugs as a breakthrough therapy for treating a large number of unmet medical needs in CNS diseases.

[0007] Despite their therapeutic potential, psilocybin and other hallucinogens remain planned abuse drugs in most countries, and the commercial pathways for their market entry as medicines are uncertain. As adjuncts to psychotherapy, the long duration of action of psilocybin and LSD makes treatment courses expensive and widespread implementation impractical. Although safe human use has a long history, several adverse events have been reported in clinical trials, and these events may be attributable to 5-HT. 2A Signal conduction bias at (primary target) or, for example, 5-HT 2B Receptor (anti-cardiac burden target) or 5-HT 1A (Anti-anxiety target) or 5-HT 2COff-target activity at receptors (e.g., disease-related targets in obesity and some hereditary epilepsy). Naturally occurring hallucinogens provide important lead structures for next-generation neurotherapeutic agents with novel mechanisms of action and / or superior clinical efficacy compared to currently available neuropsychiatric drugs.

[0008] Given the foregoing, there remains a need to develop new compounds that can be used to treat mental illnesses or central nervous system disorders.

[0009] References to any prior art in this specification do not imply an acknowledgment or implication that such prior art constitutes part of common common knowledge in any jurisdiction, nor do they imply that such prior art can be reasonably understood, regarded as related to, and / or combined with other prior art by a person skilled in the art. Summary of the Invention

[0010] International application PCT / AU2022 / 051591 describes compounds with potential efficacy in treating mental illnesses or central nervous system disorders. The compounds described herein are in 5HT... 2A The compound exhibits surprisingly high activity at the serotonin receptor. 2A The selectivity may also be surprisingly higher than that for 5HT. 2B and / or 5HT 2C Selectivity of serotonin receptors. Preferred compounds for 5HT. 2A The selectivity may also be surprisingly higher than that for 5HT. 2B and 5HT 2C The serotonin receptor exhibits selectivity in both cases. Furthermore, the compounds described herein can surprisingly possess enhanced metabolic stability while maintaining desirable activity. Therefore, the compounds described herein could also be used to treat mental illnesses or central nervous system disorders.

[0011] In one aspect, this disclosure provides a compound of formula (I): (I) Or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug. in R 1 and R 2 Each is independently selected from hydrogen and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the nitrogen atom it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them, together with the atoms it is attached to, forms C. 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; R7 R 8 R 9 R 10 and R 11 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; Alternatively, in X 2 For CR 7 At that time, R 7 and R 1 R 2 Or R 3 One of them combines with the atoms it is attached to to form C 5-8 Heterocyclic alkyl groups The C 5-8The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Alternatively, in X 1 For NR 6 And X 2 For CR 7 At that time, R 7 and R 6 It combines with the atoms it is attached to to form C 4-10 Heterocyclic alkyl or C 5-10 Mixed aromatics, The C 4-10 Heterocyclic alkyl groups and the C 5-10 Each heteroaryl group may be further optionally substituted by one or more substituents selected from the following: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Alternatively, in Z 1 For CR 8 And Z 2 For CR 9 At that time, or in Z 2 For CR 9 And Z 3 For CR 10 At that time, or in Z 3 For CR 10 And Z 4 For CR 11 When, then R 8 and R 9 、or R 9 and R 10 Or R 10 and R 11 It combines with the atoms it is attached to to form C 4-8 cycloalkyl, C 5-8 Heterocyclic alkyl, C 6-12 Aryl or C 5-10 Mixed aromatics, The C 4-8 cycloalkyl, the C 5-8 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each heteroaryl group may be further optionally substituted by one or more substituents selected from the following: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Each R 14Independently selected from hydrogen and C 1-6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics; The C 1-6 Alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C1-C6 haloalkyl, the C3-C7 cycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heteroalkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3.

[0012] In the examples of compounds of formula (I), R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 2 Independently selected from hydrogen and C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7 Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; One or more substituents R 7 R 8 R 9 R 10 and R 11 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; 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 the embodiments, the compound of formula (I) is not any of the following: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0015] In the embodiments, the compound of formula (I) is not any of the following: , , , , , , , and .

[0016] In another aspect, this disclosure provides a medicament comprising a compound according to 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, this disclosure provides a pharmaceutical composition comprising a compound according to 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, this disclosure provides a pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, a solvate, a tautomer, an N-oxide, a stereoisomer, a metabolite, a polymorph or a prodrug, an additional therapeutic agent, and a pharmaceutically acceptable excipient, according to any one of the embodiments disclosed herein.

[0019] In another aspect, this disclosure provides a method for treating a disease, condition, or symptom by activating a serotonin receptor, the method comprising administering to a subject in need a compound of formula (I) or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0020] In another aspect, this disclosure provides a method for treating a disease, condition, or symptom by activating a serotonin receptor, the method comprising administering to a subject in need a combination of a compound of formula (I) as defined in any of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, with another known agent that can be used to treat a disease, condition, or symptom by activating a serotonin receptor.

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

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

[0023] In another aspect, this disclosure provides a method for treating central nervous system (CNS) diseases, conditions or symptoms and / or neurological diseases, conditions or symptoms, the method comprising administering to a subject in need a compound of formula (I) as defined in any of the examples disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof.

[0024] In some embodiments, the CNS disease, condition, or symptom and / or the neurological disease, condition, or symptom is selected from neurological diseases including neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease; early-onset dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment; Parkinson's disease and Parkinson-related conditions such as Parkinson's dementia, corticobasal degeneration and supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial diseases; Fragile X syndrome; Angelman syndrome; hereditary ataxia; neurogenic ear and eye movement disorders; neurodegenerative diseases of retinal myofascitis; tardive dyskinesia; ADHD; attention deficit hyperactivity disorder and attention deficit disorder; restless legs syndrome; Tourette's syndrome. 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, trichotillomania, scratching, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology; and combinations thereof.

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

[0026] In another aspect, this disclosure provides a method for treating weight, the method comprising administering an effective amount of the compound of the invention to a subject in need. Treating weight may include treating weight gain; weight loss; metabolic disorders; weight gain associated with drug intervention; weight gain associated with mental illness (including the mental illnesses described herein); eating disorders such as anorexia, bulimia, cachexia, etc.; eating behaviors; obesity; diabetes; insulin resistance; prediabetes; glucose intolerance; hyperlipidemia; and cardiovascular disease.

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

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

[0029] Unless otherwise expressly stated, any embodiments herein should be considered applicable to any other embodiments after necessary modifications.

[0030] The scope of this disclosure is not limited to the specific embodiments described herein, which are for illustrative purposes only. Functionally equivalent products, compositions, and methods as described herein are clearly within the scope of this invention.

[0031] Further aspects of the invention and further embodiments of the aspects described in the foregoing paragraphs will become apparent from the following description, which is given by way of example and with reference to the accompanying drawings. Attached Figure Description

[0032] Figure 1 Plasma concentrations of a subset of example compounds P-8, P-5, P-3, and P-1, as described in Example 76, after administration at 10 mg / kg IP in male C57BL / 6 mice.

[0033] Figure 2 HTR counts and mean ± SD (n = 3) HTR counts in time bins of a subset of example compounds P-4, P-3 and P-1 after administration of several doses of SC as described in Example 77 in male C57BL / 6 mice.

[0034] Figure 3 : Showing the mean ± SD (n = 3) temperature results for a subset of example compounds P-4, P-3 and P-1 after administration of several doses of SC as described in Example 77 in male C57BL / 6 mice.

[0035] Figure 4 : Shows the mean ± SD (n = 3) HTR counts of a subset of example compounds P-4, P-3 and P-1 after administration of several doses of SC as described in Example 77 in male C57BL / 6 mice (total distance).

[0036] Figure 5 : Shows the mean ± SD (n = 3) HTR counts of a subset of example compounds P-4, P-3 and P-1 after administration of several doses of SC as described in Example 77 in male C57BL / 6 mice (distance / time).

[0037] Figure 6 The results of time-fixed reactions of compounds P-3.2HCl (3 mg / kg; 10 mg / kg; 30 mg / kg) and P-8.2HCl (3 mg / kg; 10 mg / kg; 30 mg / kg) from the tail suspension test (TST) experiment described in Example 78, compared with ketamine (10 mg / kg) and the mediator. Detailed Implementation

[0038] It should be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more features mentioned or apparent in the text or drawings. All these different combinations constitute various alternative aspects of the invention.

[0039] definition For the purposes of interpreting this specification, terms used in the singular will also include the plural form, and vice versa.

[0040] As used herein, unless the context otherwise requires, the term “comprise” and variations thereof, such as “comprising,” “comprises,” and “comprised,” are not intended to exclude additional additives, components, integers, or steps.

[0041] The term "treatment" or "treating" refers to any indication of successful treatment or improvement of an injury, pathology, or condition, including any objective or subjective parameter such as reduction; remission; a decrease in the rate of deterioration; a reduction in the severity of the disease; stabilization; a decrease in the signs or symptoms of the disease or condition; or a reduction in the risk (or susceptibility) to the disease or condition. The term "treatment" also refers to any indication of successful treatment or improvement of an injury, pathology, or condition, including any objective or subjective parameter such as reduction; remission; a decrease in the rate of deterioration; a decrease in the severity of the disease; stabilization; a reduction in the signs or symptoms of the disease or condition; or making the injury, pathology, or condition more tolerable for the individual; a slowing of the rate of degeneration or decline; or making the final stages of degeneration less debilitating.

[0042] In a particularly preferred embodiment, the method of the present invention can prevent the signs or symptoms of the disease or condition described herein, or reduce the severity of said signs or symptoms, or inhibit or minimize the progression of said signs or symptoms. Therefore, the method of the present invention can be used for both treatment and prevention.

[0043] As used herein, “preventing” or “prevention” is intended to refer to at least a reduction in the likelihood of acquiring a disease or condition (i.e., preventing an individual who may be exposed to or susceptible to a disease but has not yet experienced the disease or shown signs or symptoms of the disease from developing at least one of the clinical signs or symptoms of the disease). This article provides biological and physiological parameters for identifying such patients, and these parameters are also well known to physicians.

[0044] In this context, the terms "subject" and "patient" are used interchangeably. The terms "individual" and "patient" refer to animals, including but not limited to, humans and non-human primates, that can be treated by the compound and / or method, respectively. Unless otherwise stated, "subject" or "patient" can include both male and female sexes. Furthermore, it includes subjects or patients, preferably humans, who are suitable to receive treatment using the pharmaceutical composition and / or method of the present invention.

[0045] The term "selectivity" refers to greater activity against a first target (e.g., a second 5-HT receptor subtype) relative to a second target (e.g., a second 5-HT receptor subtype). In some embodiments, the selectivity of the compound against the first target is 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 that against the second target. In some embodiments, the selectivity is relative to one or more other 5-HT receptor subtypes (e.g., 5-HT... 2B and / or 5-HT 2C Preferably 5-HT 2B The compounds described in this paper are effective against 5-HT. 2A The receptor is selective. In some embodiments, it is selective relative to one or more other 5-HT receptor subtypes (such as 5-HT4). 2A and / or 5-HT 2B Preferably 5-HT 2B The compounds described in this paper are effective against 5-HT. 2C Receptors are selective.

[0046] When referring to measurable values ​​such as quantity or duration, as used herein, “about” is intended to cover variations of ±20% or ±10%, in some cases ±5%, in some cases ±1%, and in some cases ±0.1% relative to a specified value, as such variations are appropriate for the disclosed methods.

[0047] Scope: Throughout this disclosure, various aspects of the invention may be presented in a scope format. It should be understood that the scope format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention. Therefore, a description of a scope should be considered to have all possible sub-scopes of the specific disclosure as well as individual numerical values ​​within said scope. For example, a description of a scope such as 1 to 6 should be considered to have specific disclosed sub-scopes such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual quantities within said scope, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the scope.

[0048] As used herein, the term "alkyl" refers to a straight-chain or branched hydrocarbon group having one to twelve carbon atoms or any range thereof, i.e., containing 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms. Alkyl groups are optionally substituted with substituents. Examples of "alkyl" as used herein include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, etc.

[0049] As used herein, the terms “C1-C2 alkyl,” “C1-C3 alkyl,” and “C1-C6 alkyl” mean, as defined herein, an alkyl group containing at least one and at most two, three, or six carbon atoms, or any range thereof (e.g., alkyl groups containing two to five carbon atoms are also in the C1-C6 range).

[0050] The term "alkylene" refers to a straight-chain or branched aliphatic group having the indicated number of carbon atoms and being bonded to at least two other groups, namely divalent hydrocarbon groups. The two parts bonded to the alkylene group can be connected to the same atoms or different atoms of the alkylene group. For example, a straight-chain alkylene group can be -(CH2). n - a divalent group, where n is 1, 2, 3, 4, 5, or 6. Representative alkylene groups include, but are not limited to, methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, pentylene, and hexylene.

[0051] The term "alkenyl," whether used alone or as part of another group, refers to a straight-chain or branched saturated alkylene group, that is, a saturated carbon chain with substituents at both ends. The number of carbon atoms that may be located in the cited alkylene group is prefixed with "C".n1-n2 " indicates. For example, the term C" indicates... 2-6 Alkylene refers to an alkylene group having 2, 3, 4, 5, or 6 carbon atoms. Examples of alkenyl include, but are not limited to, vinyl, ethenyl, 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-hextrienyl.

[0052] As used herein, the term "alkynyl," whether used alone or as part of another group, refers to a straight-chain or branched unsaturated alkynyl group containing at least one triple bond. The number of carbon atoms that may be located in the cited alkyl group is prefixed with "C". n1-n2 " indicates. For example, the term C" indicates... 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, ethynyl, propynyl, 1-butynyl, 2-butynyl, butyrynyl, 1-pentynyl, 2-pentynyl, isopentenynyl, 1,3-pentyrynyl, 1,4-pentyrynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hextriynyl.

[0053] The term "cycloalkyl" is intended to include monocycloalkyl, bicycloalkyl, or tricycloalkyl. The number of carbon atoms that may be present in the cited cycloalkyl group is prefixed with "C". n1-n2 " indicates. For example, the term C" indicates... 3-8 Cycloalkyl means 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 bridged spirocyclic and fused cycloalkyl ring systems. Examples of bicyclic and tricyclic cycloalkyl systems include, but are not limited to, bicyclic [3.1.0]hexyl, bicyclic [2.1.1]hexyl, bicyclic [2.2.1]heptyl, adamantyl, and decahydronaphthyl.

[0054] The term "alkylenecycloalkyl" refers to a group having an alkyl component and a cycloalkyl component, wherein the alkyl component connects the cycloalkyl component to a linking point. The alkyl component is as defined above, except that it is at least a divalent alkylene group used for connection with the cycloalkyl component and the linking point. In some cases, the alkyl component may be absent. The alkyl component may include any number of carbons, such as C10. 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 . Cycloalkyl components are as defined herein. “C x-y The numerical range of x to y in "alkylenecycloalkyl" refers to the total number of alkyl carbon atoms and cycloalkyl ring atoms. Exemplary alkylenecycloalkyl groups include, but are not limited to, methylenecyclopropyl, methylenecyclobutyl, methylenecyclopentyl, and methylenecyclohexyl.

[0055] The term "aryl" refers to an aromatic ring system having any suitable number of ring atoms and any suitable number of rings. The number of carbon atoms that may be located in the cited aryl group is prefixed with "C". n1-n2 " indicates. For example, the term C" indicates... 6-12 Aryl refers to an aryl group having 6, 7, 8, 9, 10, 11, or 12 carbon atoms. Aryl groups can include any suitable number of ring atoms (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 ring atoms) and 6 to 10, 6 to 12, or 6 to 14 ring members. Aryl groups can be monocyclic, fused to form bicyclic or tricyclic groups, or linked by bonds to form biaryl groups. Representative aryl groups include phenyl, naphthyl, and biphenyl. Other aryl groups include benzyl with a methylene linking group. Some aryl groups have 6 to 12 ring members, such as phenyl, naphthyl, or biphenyl. Other aryl groups have 6 to 10 ring members, such as phenyl or naphthyl. Some other aryl groups have 6 ring members, such as phenyl.

[0056] The term "alkylene aryl" refers to a group having an alkyl component and an aryl component, wherein the alkyl component connects the aryl component to a linking point. The alkyl component is as defined above, except that it is at least a divalent alkylene group used for connection with the aryl component and the linking point. The alkyl component may include any number of carbons, such as C10. 1-6 C 1-2C 1-3 C 1-4 C 1-5 C 1-6 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 In some cases, the alkyl component may be absent. The aryl component is as defined above. "C x-y The numerical range of x to y in "alkylaryl" refers to the total number of alkyl carbon atoms and aryl ring atoms. Examples of alkylaryl groups include, but are not limited to, benzyl and ethylphenyl.

[0057] As used herein, the term "alkoxy" refers to an alkyl group covalently bonded by an O bond as defined herein. Alkoxy groups may optionally be substituted with substituents. Examples of "alkoxy" as used herein include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, and pentoxy.

[0058] As used herein, the terms “C1-C2 alkoxy,” “C1-C3 alkoxy,” and “C1-C6 alkoxy” mean, as defined herein, an alkoxy group containing at least one and at most two, three, or six carbon atoms, or any range thereof (e.g., alkoxy groups containing two to five carbon atoms are also in the C1-C6 range).

[0059] As used herein, the term "alkylamine" refers to an alkyl group having one or more amino groups as defined herein. The amino group can be a primary, secondary, or tertiary amino group. Alkylamines can be further substituted with a hydroxyl group to form an amino-hydroxy group. Examples of alkylamines include, but are not limited to, ethylamine, propylamine, isopropylamine, ethylenediamine, and ethanolamine. The amino group can connect the alkylamine to the linking point and the rest of the compound, can be located at the ω-position of the alkyl group, or can connect at least two carbon atoms of the alkyl group together.

[0060] As used herein, the terms “C1-C2 alkylamine,” “C1-C3 alkylamine,” and “C1-C6 alkylamine” refer to alkylamines as defined herein that contain at least one and at most two, three, or six carbon atoms, or any range thereof (e.g., alkylamines containing two to five carbon atoms are also in the C1-C6 range).

[0061] As used herein, the term "alkylsulfonyl" means an alkyl group having one or more sulfonyl groups as defined herein. A sulfonyl group can be attached to the alkylsulfonyl group at a linking point and the remainder of the compound, can be located at the ω position of an alkyl group, or can connect at least two carbon atoms of an alkyl group together.

[0062] As used herein, the terms “C1-C2 alkylsulfonyl,” “C1-C3 alkylsulfonyl,” and “C1-C6 alkylsulfonyl” mean, as defined herein, an alkylsulfonyl group containing at least one and at most two, three, or six carbon atoms, or any range thereof (e.g., an alkylsulfonyl group containing 2 to 5 carbon atoms is also in the C1-C6 range).

[0063] As used herein, the term "heteroatom" refers to 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 / or S, with N and O being more preferred.

[0064] As used herein, the term "heterogeneous moiety" refers to a chemical group that contains a heteroatom. Examples of heterogeneous moiety include O, S, S(O), SO2, N, and NH.

[0065] As used herein, a “substituent” refers to a molecular moiety covalently bonded to an atom within the molecule of interest. References to “substituent” may include a single substituent or one or more substituents from a specified list. In some embodiments, the substituted moiety 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 only one substituent. For example, a “cyclic substituent” may be a ring member moiety covalently bonded to an atom, preferably a carbon or nitrogen atom, such as a halogen, alkyl, or other substituent described herein. As used herein, the term “substituted” means that any one or more hydrogen atoms on a specified atom are replaced by an alternative from an indicated substituent, provided that the replacement does not exceed the normal valence of the specified atom, and that the substitution produces a stable compound, i.e., a compound that can be isolated, characterized, and tested for biological activity.

[0066] As used throughout this specification, terms such as “optionally substituted” or “may be substituted” indicate that a group may or may not be further substituted by one or more non-hydrogen substituents or fused with said one or more non-hydrogen substituents (to form a polycyclic system). Suitable chemically feasible substituents for a particular functional group will be apparent to those skilled in the art.

[0067] Examples of substituents include, but are not limited to, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C3-C7 heterocyclic, C3-C7 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylthioalkyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonylamino, arylsulfonylamino, alkylcarboxyl, alkylformamide, oxo, hydroxyl, mercapto, amino, acyl, carboxyl, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, arylyl, arylamide, heteroarylyl, acyloxy, arylyloxy, heteroaryloxy, alkoxycarbonyl, nitro, cyano, halogenated, urea, and C1-C6 perfluoroalkyl. Preferably, the substituents include amino, halogenated, C1-C6 alkyl, amino, and hydroxyl.

[0068] As used herein, the term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I), and the term "halogenated" refers to the halogen group fluorinated (-F), chlorinated (-Cl), bromine (-Br), and iodinated (-I). Preferably, "halogenated" is fluorinated or chlorinated.

[0069] As used herein, the term "haloalkyl" refers to an alkyl group in which one or more (at most all) of its available hydrogen atoms have been replaced by a halogen, as defined herein. In some cases, the term "perfluorinated" may be used to define a compound or group in which all of its hydrogen atoms have been replaced by fluorine. For example, perfluoromethyl refers to 1,1,1-trifluoromethyl.

[0070] As used herein, the terms “C1-C2 haloalkyl,” “C1-C3 haloalkyl,” and “C1-C6 haloalkyl” mean, as defined herein, a haloalkyl containing at least one and at most two, three, or six carbon atoms, or any range thereof (e.g., haloalkyl containing two to five carbon atoms is also in the C1-C6 range).

[0071] For example, the C1 haloalkyl group can be, but is not limited to, fluoromethyl, difluoromethyl, or trifluoromethyl.

[0072] As used herein, the term "haloalkenyl" refers to one or more (at most all) alkenyl groups as defined above in which available hydrogen atoms have been replaced by halogens. Thus, for example, "C..." 1-6 "Haloalkenyl" (or "C1-C6 haloalkenyl") refers to a C1 to C6 straight-chain or branched alkenyl group having one or more halogen substituents as defined above.

[0073] As used herein, the term "haloalkynyl" refers to an alkynyl group in which one or more (at most all) of the available hydrogen atoms have been replaced by a halogen, as defined above. Thus, for example, "C..." 1-6"Haloalkynyl" (or "C1-C6 haloalkynyl") refers to a C1 to C6 straight-chain or branched alkynyl group having one or more halogen substituents as defined above.

[0074] As used herein, the term haloalkoxy means an alkoxy group that is substituted with at least one halogen, as defined herein.

[0075] The term "amino" or "amine" refers to the -NH2 group.

[0076] The term "substituted amino" or "secondary amino" refers to an amino group in which hydrogen is replaced by, for example, a C1-C6 alkyl group ("C1-C6 alkylamino"), an aryl group, or an aralkyl group ("arylamino", "aralkylamino"), etc. C1-C3 alkylamino groups are preferred, such as methylamino (NHMe), ethylamino (NHEt), and propylamino (NHPr).

[0077] The term "disubstituted amino" or "tertiary amino" refers to an amino group in which both hydrogen atoms are replaced by, for example, C1-C6 alkyl groups (which may be the same or different ("dialkylamino")), aryl and alkyl groups ("aryl(alkyl)amino"), etc. Di(C1-C3 alkyl)amino is preferred, for example, dimethylamino (NMe2), diethylamino (NEt2), dipropylamino (NPr2) and its variants (e.g., N(Me)(Et) etc.).

[0078] The term "nitro" refers to the group -NO2.

[0079] The terms "cyano" and "nitrile" refer to the -CN group.

[0080] The terms "amine" or "amide" refer to the group -C(O)NH2.

[0081] The terms "substituted amino group" or "substituted amide" refer to an amino group in which hydrogen is replaced by, for example, a C1-C6 alkyl group ("C1-C6 alkylamino group" or "C1-C6 alkylamide group"), an aryl group ("arylamino group"), an aralkyl group ("aralkylamino group"), etc. 1- C3 alkyl amide groups are preferred, such as methylamide (-C(O)NHMe), ethylamide (-C(O)NHEt) and propylamide (-C(O)NHPr), and include their reverse amides (e.g. NHMeC(O)-, -NHEtC(O)- and -NHPrC(O)-).

[0082] The terms "disubstituted amino group" or "disubstituted amide" refer to an amino group in which both hydrogen atoms are replaced by, for example, C1-C6 alkyl groups ("di(C1-C6 alkyl)amino" or "di(C1-C6 alkyl)amide"), aralkyl groups, and alkyl groups ("alkyl(aralkyl)amino"). Di(C1-C3 alkyl)amide groups are preferred, for example, dimethylamide (-C(O)NMe2), diethylamide (-C(O)NEt2), and dipropylamide (-C(O)NPr2), as well as their variants (e.g., C(O)N(Me)Et, etc.), and include their reverse amides.

[0083] The term "sulfonyl" refers to the group -SO2H.

[0084] The term "substituted sulfonyl" refers to a sulfonyl group in which the hydrogen is replaced by, for example, a C1-C6 alkyl group ("sulfonyl C1-C6 alkyl"), an aryl group ("aryl sulfonyl"), or an aralkyl group ("aralkyl sulfonyl"). The sulfonyl group C 1- C3 alkyl groups are preferred, for example, -SO2Me, -SO2Et and -SO2Pr.

[0085] The terms "sulfonylamine" or "sulfonamide" refer to the group -SO2NH2.

[0086] The terms "substituted sulfonamide" or "substituted sulfonamide" refer to a sulfonamide group in which the hydrogen is replaced by, for example, a C1-C6 alkyl group ("sulfonamide C1-C6 alkyl"), an aryl group ("aryl sulfonamide"), an aralkyl group ("aralkyl sulfonamide"), etc. A sulfonamide C1-C3 alkyl group is preferred, for example, SO2NHMe, SO2NHEt, and -SO2NHPr, and includes its reverse sulfonamide (e.g., -NHSO2Me, NHSO2Et, and -NHSO2Pr).

[0087] The terms "disubstituted sulfonamide" or "disubstituted sulfonamide" refer to a sulfonamide group in which both hydrogens are replaced by, for example, a C1-C6 alkyl group (which may be the same or different ("sulfonamide di(C1-C6)alkyl")), an aralkyl group, and an alkyl group ("sulfonamide (aralkyl)alkyl"). A sulfonamide di(C1-C3) group is preferred, for example, -SO2NMe2, -SO2NEt2, and -SO2NPr2, and their variants (e.g., SO2N(Me)Et, etc.), and includes its reverse sulfonamide (e.g., -N(Me)SO2Me, etc.).

[0088] The term "sulfate" refers to the group OS(O)2OH, and includes groups in which hydrogen is replaced by groups such as C1-C6 alkyl ("alkyl sulfate"), aryl ("aryl sulfate"), aralkyl ("aralkyl sulfate"), etc. C1-C3 alkyl sulfates are preferred, for example, OS(O)2OMe, OS(O)2OEt and S(O)2OPr.

[0089] The term "sulfonate" refers to the group SO3H and includes groups in which hydrogen is replaced by groups such as C1-C6 alkyl ("alkyl sulfonates"), aryl ("aryl sulfonates"), aralkyl ("aralkyl sulfonates"), etc. C1-C3 alkyl sulfonates are preferred, for example, SO3Me, SO3Et and SO3Pr.

[0090] As defined herein, the term "amino acid" refers to a moiety containing an amino group and a carboxyl group linked by at least one carbon atom. Amino acids can 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, with lysine being the most preferred.

[0091] The terms "carboxylic acid ester" or "carboxyl group" refer to the group -COO- or -COOH.

[0092] The terms "carbamate" or "carbamoyl" refer to the group -OC(O)NH2. Carbamates can be substituted or can be disubstituted, for example, by alkyl groups (such as, but not limited to, C1-C6 alkyl groups) or by disubstituted groups.

[0093] The term "carbonate" refers to the group -OC(O)O- or -OC(O)OH.

[0094] As defined herein, the term "alkyl carbonate" refers to a substance in which hydrogen is, for example, C 1- Carbonates replaced by C6 alkyl, aryl, or aralkyl (“aryl carbonate” or “aralkyl carbonate”). CO3C 1- C3 alkyl groups are preferred, for example, methyl carbonate (CO3Me), ethyl carbonate (CO3Et), and propyl carbonate (CO3Pr).

[0095] The term "ester" refers to a carboxyl group in which the hydrogen is replaced by a group such as a C1-C6 alkyl group ("carboxy-C1-C6 alkyl" or "alkyl ester"), an aryl group, or an aralkyl group ("aryl ester" or "aralkyl ester"). CO2C 1-C3 alkyl groups are preferred, for example, methyl esters (CO2Me), ethyl esters (CO2Et) and propyl esters (CO2Pr), and include their reverse esters (e.g. -OC(O)Me, -OC(O)Et and -OC(O)Pr).

[0096] The term "heterocyclic group" refers to a portion obtained by removing hydrogen atoms from the ring atoms of a heterocyclic compound, said portion having 3 to 12 ring atoms (unless otherwise specified), wherein one, two, three, four or more of said ring atoms are cyclic heteroatoms (e.g., cyclic heteroatoms independently selected from O, S, and N) or cyclic heteromes, such as cyclic heteromes independently selected from O, S, S(O), SO2, N, and NH. When the heterocyclic group contains the prefix C... n1-n2 When "n1 to n2" is used, this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, in which one or more ring atoms (appropriately, 1, 2, 3, 4 or more reducers) are replaced by heteroatoms or heteroparts.

[0097] In this context, the prefixes 3, 4, 5, 6, 7, 8, 9, and 10 indicate the number or range of ring atoms, whether carbon or heteroatoms. For example, as used herein, the term "C"... 3-10 "Heterocyclic group" or "3-10 membered heterocyclic group" refers to a heterocyclic group having 3, 4, 5, 6, 7, 8, 9 or 10 ring atoms. Examples of heterocyclic groups include 5-6 membered monocyclic heterocyclic groups and 6-10 membered bicyclic heterocyclic groups (including fused, bridged and spirocyclic systems).

[0098] Examples of monocyclic heterocyclic groups include, but are not limited to, monocyclic heterocyclic groups containing one nitrogen atom, such as aziridine (3-membered ring), aziridine (4-membered ring), pyrrolidine (tetrahydropyrrole), pyrroline (e.g., 3-pyrroline, 2,5-dihydropyrrole), 2H-pyrrole or 3H-pyrrole (isopyrrole, isazole) or pyrrolidone (5-membered ring), piperidine, dihydropyridine, tetrahydropyridine (6-membered ring), and aziridine heptatriene (7-membered ring); monocyclic heterocyclic groups containing two nitrogen atoms, such as imidazoline, pyrazole (dihydropyrrole, isazole), etc. Monocyclic heterocyclic groups containing one oxygen atom include: diazolidine, imidazoline, pyrazolidine (dihydropyrazole) (5-membered ring), piperazine (6-membered ring), etc.; monocyclic heterocyclic groups containing one oxygen atom, such as ethylene oxide (3-membered ring), oxetane (4-membered ring), oxopentane (tetrahydrofuran), furan (dihydrofuran) (5-membered ring), ethylene oxide (tetrahydropyran), dihydropyran, pyran (6-membered ring), oxheptan (7-membered ring); monocyclic heterocyclic groups containing two oxygen atoms, such as dioxopentane (5-membered ring), dioxane (… Monocyclic heterocyclic groups containing three oxygen atoms, such as trioxane (6-membered ring); monocyclic heterocyclic groups containing one sulfur atom, such as cyclothioethane (3-membered ring), thiobutane (4-membered ring), thiapentane (tetrahydrothiophene) (5-membered ring), thiapanane (tetrahydrothiaran) (6-membered ring), and thiaheptane (7-membered ring); monocyclic heterocyclic groups containing one nitrogen atom and one oxygen atom, such as tetrahydrooxazole, dihydrooxazole, tetrahydroisoxazole, dihydroisoxazole (5-membered ring), morpholine, and tetrahydrooxazole. Azides, dihydrooxazines, oxazines (6-membered ring); monocyclic heterocyclic groups containing one nitrogen atom and one sulfur atom, such as thiazoline, thiazoline (5-membered ring), thiomorpholine (6-membered ring); monocyclic heterocyclic groups containing two nitrogen atoms and one oxygen atom, such as oxadiazine (6-membered ring); monocyclic heterocyclic groups containing one oxygen atom and one sulfur atom, such as oxathiazoline (5-membered ring) and thiazoline (6-membered ring); and monocyclic heterocyclic groups containing one nitrogen atom, one oxygen atom and one sulfur atom, such as oxathiazine (6-membered ring).

[0099] Heterocyclic groups also encompass heteroaryl (aromatic heterocyclic groups) and heterocyclic alkyl (non-aromatic heterocyclic groups). These groups can be substituted or unsubstituted.

[0100] The term "aromatic heterocyclic group" may be used interchangeably with the terms "heteroaromatic" or "heteroaryl". The heteroatom in an aromatic heterocyclic group can be independently selected from N, S, and O. An aromatic heterocyclic group can contain one, two, three, four, or more cyclic heteroatoms. When the heteroaryl group contains the prefix C... n1-n2When "n1 to n2" is used, this prefix indicates the number of carbon atoms in the corresponding aryl group, in which one or more ring atoms (appropriately, 1, 2, 3, 4 or more reducers) are replaced by heteroatoms. In the case of fused aromatic heterocyclic groups, only one ring may contain heteroatoms, and not all rings must be aromatic.

[0101] This document uses the term "heteroaryl" to denote a heterocyclic group possessing aromatic properties, and encompasses both aromatic monocyclic systems and polycyclic (e.g., bicyclic) systems containing one or more aromatic rings. The term aromatic heterocyclic group also encompasses quasi-aromatic heterocyclic groups. The term "quasi-aromatic" refers to a ring system that is not strictly aromatic, but is stabilized by electronic delocalization and functions in a manner similar to that of aromatic rings. Therefore, the term aromatic heterocyclic group encompasses polycyclic systems in which all fused rings are aromatic, as well as ring systems in which one or more rings are non-aromatic (provided at least one ring is aromatic). In polycyclic systems containing fused aromatic and non-aromatic rings, a group can be attached to another part via either an aromatic or non-aromatic ring.

[0102] Examples of heteroaryl groups are monocyclic and bicyclic groups containing five to ten ring members. A heteroaryl group can be, for example, a five- or six-membered monocyclic ring or a bicyclic structure formed by fused five- and six-membered rings, or two fused six-membered rings, or two fused five-membered rings. Each ring can contain up to about four heteroatoms typically selected from nitrogen, sulfur, and oxygen. The heteroaryl ring will contain up to four heteroatoms, more specifically up to three heteroatoms, and more generally up to two, such as a single heteroatom. In one embodiment, the heteroaryl ring contains at least one cyclic nitrogen atom. The nitrogen atom in the heteroaryl ring can be basic, as in the case of imidazole or pyridine, or substantially non-basic, as in the case of indole or pyrrole nitrogen. Typically, the number of basic nitrogen atoms present in the heteroaryl group (including any amino substituents in the ring) will be less than five.

[0103] Aromatic heterocyclic groups can be 5- or 6-membered monocyclic aromatic ring systems.

[0104] Examples of 5-membered monocyclic heteroaryl groups include, but are not limited to, furanyl, thiophene, pyrrole, oxazolyl, oxadiazolyl (including 1,2,3 and 1,2,4 oxadiazolyl and furanyl, i.e., 1,2,5-oxadiazolyl), thiazolyl, isoxazolyl, isothiazolyl, pyrazolyl, imidazole, triazolyl (including 1,2,3, 1,2,4 and 1,3,4 triazolyl), oxtriazolyl, tetrazolyl, thiadiazolyl (including 1,2,3 and 1,3,4 thiadiazolyl), etc.

[0105] Examples of 6-membered monocyclic heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, pyranyl, oxazinyl, dioxinyl, thiazidinyl, and thiadiazidinyl. Examples of nitrogen-containing 6-membered aromatic heterocyclic groups include pyridinyl (1 nitrogen atom), pyrazinyl, pyrimidinyl, and pyrazinyl (2 nitrogen atom).

[0106] Aromatic heterocyclic groups can also be bicyclic or polycyclic heteroaromatic ring systems, such as fused ring systems (including purine, pteridinyl, naphthidinyl, 1H-thieno[2,3-c]pyrazolyl, thieno[2,3-b]furanyl, etc.) or linking ring systems (such as oligothiophene, polypyrrole, etc.). Fused ring systems can also include aromatic 5- or 6-membered heterocyclic groups fused with carbocyclic aromatic rings such as phenyl, naphthyl, indole, azulel, fluorenyl, anthracene, etc., such as 5-membered aromatic heterocyclic groups containing nitrogen fused with phenyl, and 5-membered aromatic heterocyclic groups containing one or two nitrogen atoms fused with phenyl.

[0107] The bicyclic heteroaryl group can be, for example, selected from the following groups: a) a benzene ring fused to a 5- or 6-membered ring containing one, two, or three heteroatoms; b) a pyridine ring fused to a 5- or 6-membered ring containing one, two, or three heteroatoms; c) a pyrimidine ring fused to a 5- or 6-membered ring containing one or two heteroatoms; d) a pyrrole ring fused to a 5- or 6-membered ring containing one, two, or three heteroatoms; e) a pyrazole ring fused to a 5- or 6-membered ring containing one or two heteroatoms; f) an imidazole ring fused to a 5- or 6-membered ring containing one or two heteroatoms; g) a group fused to a 5- or 6-membered ring containing one or two heteroatoms. The following are listed: (a) an oxazole ring; (b) an isoxazole ring fused with a 5- or 6-membered ring containing one or two heteroatoms; (c) a thiazole ring fused with a 5- or 6-membered ring containing one or two heteroatoms; (d) an isothiazole ring fused with a 5- or 6-membered ring containing one or two heteroatoms; (e) a thiophene ring fused with a 5- or 6-membered ring containing one, two, or three heteroatoms; (f) a furan ring fused with a 5- or 6-membered ring containing one, two, or three heteroatoms; (m) a cyclohexyl ring fused with a 5- or 6-membered ring containing one, two, or three heteroatoms; and (n) a cyclopentyl ring fused with a 5- or 6-membered ring containing one, two, or three heteroatoms.

[0108] Specific examples of bicyclic heteroaryl groups containing a five-membered ring fused with another five-membered ring include, but are not limited to, imidazothiazoles (e.g., imidazo[2,1-b]thiazole) and imidazoimidazoles (e.g., imidazo[1,2-a]imidazole).

[0109] Specific examples of bicyclic heteroaryl groups containing a six-membered ring fused with a five-membered ring include, but are not limited to, benzofuran, benzothiophene, benzimidazole, benzoxazole, isobenzoxazole, benzoisoxazole, benzothiazole, benzoisothiazole, isobenzofuran, indole, isoindole, indazine, indoline, isoindoline, purine (e.g., adenine, guanine), indazole, pyrazolopyrimidine (e.g., pyrazolo[1,5-a]pyrimidine), benzodioxane, and pyrazolopyridine (e.g., pyrazolo[1,5-a]pyridine) groups. Further examples of a six-membered ring fused with a five-membered ring are pyrrolopyridine groups, such as pyrrolo[2,3-b]pyridine groups.

[0110] Specific examples of bicyclic heteroaryl groups containing two fused six-membered rings include, but are not limited to, quinoline, isoquinoline, chromium, thiochromium, chromene, isochromene, isochromium, benzodioxane, quinazine, benzoxazine, benzodiazine, pyridopyridine, quinoxaline, quinazolin, quinazolin, cyclophosphine, phthalazine, naphthidine, and pteridine groups.

[0111] 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]dicenrocene, 4,5,6,7-tetrahydrobenzofuran, indoline, isoindoline, and indane groups.

[0112] Therefore, examples of aromatic heterocyclic groups fused with carbocyclic aromatic rings may include, but are not limited to, benzothiophene, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzimidazolyl, indazole, benzoxazolyl, benisoxazolyl, isobenzoxazolyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cycloazinyl, benzotriazinyl, phthalazinyl, carbolinyl, etc.

[0113] The terms "heterocyclic alkyl" or "non-aromatic heterocyclic" encompass optionally substituted saturated and unsaturated rings containing at least one heteroatom (such as N, S, and O) or a heteromonomer, such as O, S, S(O), SO2, N, and NH. The ring may contain one, two, three, four, or more heteroatoms or heteromonomers. When a heterocyclic alkyl group contains the prefix C... n1-n2 When "n1 to n2" is used, this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, in which one or more ring atoms (suitably 1, 2, 3, 4 or more reducers) are replaced by heteroatoms or hetero-parts. The ring can be part of a monocyclic or polycyclic system. Polycyclic systems include fused rings and / or bridging rings and spirocyclic rings. Not every ring in a non-aromatic heterocyclic polycyclic system must contain a heteroatom; at least one ring may contain one or more heteroatoms.

[0114] Non-aromatic heterocyclic groups can be 3-8 membered monocyclic rings.

[0115] Examples of 5-membered non-aromatic heterocyclic rings include 2H-pyrrolidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, pyrrolidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrazolinyl, 2-pyrazolinyl, 3-pyrazolinyl, pyrazolinyl, 2-pyrazolinyl, 3-pyrazolinyl, imidazolinyl, 3-dioxolanecycloyl, thiazolinyl, isoxazolinyl, 2-imidazolinyl, etc.

[0116] Examples of 6-membered non-aromatic heterocyclic groups include piperidinyl, piperidinoneyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 2Hpyranyl, 4Hpyranyl, thiaranyl, oxythiaranyl, thiaranyl dioxide, piperazine, dioxanecycloyl, 1,4-dioxinyl, 1,4-dithiaalkyl, 1,3,5-trithiaalkyl, 1,3,5-trithiaalkyl, 1,4-morpholinyl, thiomorpholinyl, 1,4-oxothiocyclohexane, triazine, 1,4-thiaazine, etc.

[0117] Examples of 7-membered non-aromatic heterocyclic groups include azirheptanyl, epoxide hexyl, thiacycloheptanyl, etc.

[0118] Non-aromatic heterocyclic rings can also be bicyclic heterocyclic rings, such as linking ring systems (e.g., uridine groups) or fused ring systems. Fused ring systems include non-aromatic 5-, 6-, or 7-membered heterocyclic groups fused to a carbocyclic aromatic ring, such as phenyl, naphthyl, indene, azulel, fluorenyl, anthracene, etc. Examples of non-aromatic 5-, 6-, or 7-membered heterocyclic groups fused to a carbocyclic aromatic ring include indololinyl, benzodiazepine, benzozazepine, dihydrobenzofuranyl, etc.

[0119] The term "alkylene heteroaryl" refers to a group having an alkyl component and a heteroaryl component, wherein the alkyl component connects the heteroaryl component to a linking point. The alkyl component is as defined above, except that it is at least a divalent alkylene group used for connection with the heteroaryl component and the linking point. In some cases, the alkyl component may be absent. The alkyl component may include any number of carbons, such as C10. 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 Heteroaryl components are as defined herein. "C"x-y The numerical range of x to y in "alkylenecycloalkyl" refers to the total number of alkyl carbons and heteroaryl ring atoms (carbons and heteroatoms together).

[0120] The term "alkylene heterocyclic alkyl" refers to a group having an alkyl component and a heterocyclic alkyl component, wherein the alkyl component connects the heterocyclic alkyl component to a linking point. The alkyl component is as defined above, except that it is at least a divalent alkylene group used for connection with the heterocyclic alkyl component and the linking point. In some cases, the alkyl component may be absent. The alkyl component may include any number of carbons, such as C10. 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 Heterocyclic alkyl components are as defined herein. "C" x-y The numerical range of x to y in "alkylene heterocyclic alkyl" refers to the total number of alkyl carbons and heterocyclic alkyl ring atoms (carbons and heteroatoms together).

[0121] As used herein, the term solvate refers to a complex of a compound with a stoichiometric or non-stoichiometric amount of solvent. Solvates are typically formed during crystallization using pharmaceutically acceptable solvents such as water or ethanol. When the solvent is water, a hydrate is formed, or when the solvent is an alcohol, an alcohol is formed.

[0122] As used herein, the term polymorph refers to different crystalline arrangements of compounds composed of the same elements. Polymorphs typically exhibit different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, optical and electrical properties, stability, and solubility. Various factors, such as recrystallization solvents, crystallization rates, and storage temperatures, can lead to the dominance of single-crystal forms.

[0123] As used herein, the term "metabolite" refers to a derivative of a compound formed during the metabolism of the compound. The term "active metabolite" refers to a biologically active derivative of a compound formed during the metabolism of the compound. As used herein, the term "metabolizing" refers to the sum of processes by which an organism alters a particular substance (including, but not limited to, hydrolysis and enzyme-catalyzed reactions). Thus, enzymes can produce specific structural alterations to compounds. Metabolites of the compounds disclosed herein may optionally be identified by administering the compound to a host and analyzing tissue samples from the host, or by incubating the compound with hepatocytes in vitro and analyzing the resulting compound.

[0124] The stereochemical definitions and conventions used in this article generally follow the SP Parker-edited McGraw-Hill Dictionary of Chemical Terms ( 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 may exist in different stereoisomeric forms. The term “stereoisomer” refers to a compound having the same chemical composition but with different spatial arrangements of atoms or groups. As used herein, the term “stereoisomer” includes, but is not limited to, diastereomers, enantiomers, and transisomers, as well as mixtures thereof, such as racemic mixtures.

[0125] As used herein, the term "pharmaceutically acceptable salt" means that salts suitable for contact with tissues of humans and lower animals within the bounds of reasonable medical judgment without excessive toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al. describe pharmaceutically acceptable salts in detail in the *Journal of Pharmaceutical Sciences*, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are amino-containing salts formed with inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or with 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 adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentylpropionate, diglucuronate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucohepanoate, glycerophosphate, glucuronate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, dodecyl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0126] compound This disclosure provides compounds of formula (I): (I) Or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug. in R 1 and R 2 Each is independently selected from hydrogen and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the nitrogen atom it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them, together with the atoms it is attached to, forms C. 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; R7 R 8 R 9 R 10 and R 11 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; Alternatively, in X 2 For CR 7 At that time, R 7 and R 1 R 2 Or R 3 One of them combines with the atoms it is attached to to form C 5-8 Heterocyclic alkyl groups The C 5-8The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Alternatively, in X 1 For NR 6 And X 2 For CR 7 At that time, R 7 and R 6 It combines with the atoms it is attached to to form C 4-10 Heterocyclic alkyl or C 5-10 Mixed aromatics, The C 4-10 Heterocyclic alkyl groups and the C 5-10 Each heteroaryl group may be further optionally substituted by one or more substituents selected from the following: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Alternatively, in Z 1 For CR 8 And Z 2 For CR 9 At that time, or in Z 2 For CR 9 And Z 3 For CR 10 At that time, or in Z 3 For CR 10 And Z 4 For CR 11 When, then R 8 and R 9 、or R 9 and R 10 Or R 10 and R 11 It combines with the atoms it is attached to to form C 4-8 cycloalkyl, C 5-8 Heterocyclic alkyl, C 6-12 Aryl or C 5-10 Mixed aromatics, The C 4-8 cycloalkyl, the C 5-8 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each heteroaryl group may be further optionally substituted by one or more substituents selected from the following: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Each R 14Independently selected from hydrogen and C 1-6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics; The C 1-6 Alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C1-C6 haloalkyl, the C3-C7 cycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heteroalkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3.

[0127] In some embodiments, R 8 and R 9 One of them (if present) is selected from halogen, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl and C 1-6 The alkyl halide, and the other (if present) is hydrogen.

[0128] In some embodiments, R 8 (If present) Selected from halogens, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl and C 1-6 Halogenated alkyl groups, and R 9 (If it exists) is hydrogen.

[0129] In some embodiments, R 9 (If present) Selected from halogens, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl and C 1-6 Halogenated alkyl groups, and R 8 (If it exists) is hydrogen.

[0130] In some embodiments, R 8 (If present) Selected from halogens, OR 13 and C 1-6 Alkyl, and R 9 (If it exists) is hydrogen.

[0131] In some embodiments, R 9 (If present) Selected from halogens, OR 13 and C 1-6 Alkyl, and R 8 (If it exists) is hydrogen.

[0132] In some embodiments, R 8 and R 9 One of them is OR 13 .

[0133] In some embodiments, each R 13 (If present) Independently selected from hydrogen and C 1-6 alkyl.

[0134] In some embodiments, each R 13 (If it exists) is H.

[0135] In some embodiments, each R 13 (If it exists) is C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably methyl.

[0136] In some embodiments, R 7 (If it exists) is hydrogen.

[0137] In some embodiments, R 8 (If it exists) is hydrogen.

[0138] In some embodiments, R 9 (If it exists) is hydrogen.

[0139] In some embodiments, R 10 (If it exists) is hydrogen.

[0140] In some embodiments, R 7 and R 8 (If it exists) is hydrogen.

[0141] In some embodiments, R 7 and R 10 (If it exists) is hydrogen.

[0142] In some embodiments, R 8 and R 10 (If it exists) is hydrogen.

[0143] In some embodiments, R 7 R 8 and R 10 (If it exists) is hydrogen.

[0144] In some embodiments, R 8 R 9 and R 10 Only one of (if present) is not hydrogen. In some embodiments, R 8 R 9 and R 10 (If it exists) only R 8 Not hydrogen. In some embodiments, R 8 R 9 and R 10 (If it exists) only R 9 Not hydrogen. In some embodiments, R 8 R 9 and R 10 (If it exists) only R 10 It is not hydrogen.

[0145] 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.

[0146] In some embodiments, R 1 and R 2 Each is independently selected from hydrogen and C. 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 The atoms it is attached to combine to form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, CO2R 4 C(O)N(R) 4 2. OR4 、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 group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7 Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; R 7 Selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; Alternatively, R 7 and R 1 R 2 Or R 3 One of them combines with the atoms it is attached to to form C 5-8 Heterocyclic alkyl groups The C 5-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (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 142. NO2, SR 14 SO2R 14 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; R 8 R 9 and R 10 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 132. NO2, C 3-8 cycloalkyl, C 3-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; Alternatively, R 8 and R 9 Or R 9 and R 10 It combines with the atoms it is attached to to form C 4-8 cycloalkyl, C 5-8 Heterocyclic alkyl, C 6-12 Aryl or C 5-10 Mixed aromatics, The C 4-8 cycloalkyl, the C 5-8 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each heteroaryl group may be further optionally substituted by one or more substituents selected from the following: halogen, (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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 14 ; Each R 14 Independently selected from hydrogen and C 1-6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics; The C 1-6 Alkyl, the C2-C6 alkenyl, the C2-C6 alkynyl, the C1-C6 haloalkyl, the C3-C7 cycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heteroalkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3.

[0147] In some embodiments, R 1 and R 2 Each is independently selected from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl and C 4-14 Alkylene cycloalkylene.

[0148] In some embodiments, R 1 and R 2 Each is independently selected from C 1-4 alkyl.

[0149] In some embodiments, R 1 and R 2 Together with the nitrogen it is attached to, it forms any of the following: , , , , , , , , , , , , , , , , , , , and .

[0150] In some embodiments, R 1 and R 2 The atoms it is attached to combine to form C 3-6 Heterocyclic alkyl, the C 3-6 The heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 , where R 4 As defined in any of the preceding paragraphs.

[0151] In some embodiments, R 3 It is hydrogen.

[0152] In some embodiments, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-8 Heterocyclic alkyl, the C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 42. 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 group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 , where R 4 As defined in any of the preceding paragraphs.

[0153] In some embodiments, R 7 R 8 R 9 and R 10 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. SO2R 13 、N(R 13 )2、N(R 13 )C(O)R 13 、N(R13 )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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Where R 13 As defined in any of the preceding paragraphs.

[0154] In some embodiments, R 7 R 8 R 9 and R 10 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, CO2R 13 C(O)N(R) 13 2. OC(O)R 13 OSO2R 13 OP(O)(OR) 13 2. OC 1-6 Alkylene 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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, The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; Where R 13 As defined in any of the preceding paragraphs.

[0155] In some embodiments, R7 R 8 R 9 and R 10 One or two of them are independently selected from halogens, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and OR 13 , where R 13 Selected from C 1-6 Alkyl and C 1-6 Halogenated alkyl groups, and R 7 R 8 R 9 and R 10 The other elements are each hydrogen.

[0156] Other embodiments In the embodiments, the compounds of the present invention are compounds of formula (I): (I) in: R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8Alkoxy, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 2 Independently selected from hydrogen and C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 4SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7 Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; One or more substituents R 7 R 8 R 9 R 10 and R 11 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R)13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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(R13 2. NO2, SR 13 and SO2R 13 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heteroalkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3.

[0157] In the embodiments, the compound of formula (I) is not any of the following: , , , , , , , and .

[0158] In some embodiments, R 7 For H, R 8 For H, and R 10 For H. In these embodiments, the compound may be provided by formula (II): (II) Where R 1 R 2 R 3 and R 9 As defined in any aspect or embodiment of this document.

[0159] R 1 R 2 and R 3 In the embodiment, R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 2 Independently selected from hydrogen and C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; In the embodiment, R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

[0160] In the embodiment, R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, The C 1-6 Alkyl, the C 1-6 Each haloalkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 .

[0161] In the embodiment, R 2 Selected independently from C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

[0162] In the embodiment, R 1 and R 2 At least one of them is not hydrogen.

[0163] In the embodiment, R 1 and R 2 Neither of them is hydrogen. In the examples, R 1 and R 2 Either of them is hydrogen.

[0164] In the embodiment, R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

[0165] In the embodiment, R 1 and R 2 Together with the nitrogen atom it is attached to, they form C 4-8 Heterocyclic alkyl, the C 4-8 Heterocyclic alkyl groups include 0 or 1 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 Wherein C 4-8 The heterocyclic alkyl group is optionally substituted by one or more substituents selected from the following: halogen, C 1-8 Alkoxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

[0166] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms an optionally substituted C 4-8 Heterocyclic alkyl groups. In these embodiments, compounds of formula (I) may be provided as compounds of formula (III): (III) in: R 3 and R 9 As defined in any aspect or embodiment herein; n is an integer from 1 to 5, preferably 1, 2, or 3; and Each R can be the same or different, and is independently selected from hydrogen, halogen, C. 1-8 Alkoxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 3-6Heterocyclic alkyl groups, or two R groups together with the atoms they are attached to form optionally substituted C groups. 4-12 Cycloalkyl or optionally substituted 4-12 membered heterocyclic alkyl rings can thus form fused, spirocyclic, or bridged cyclic systems. In the examples, two Rs bonded to the same ring carbon atom form optionally substituted Cs. 4-12 A cycloalkyl or optionally substituted 4-12 membered heterocyclic alkyl ring is used to form a spirocyclic ring system. Preferably, the two R atoms bonded to the same ring carbon atom form an optionally substituted C. 4-6 Cycloalkyl or optionally substituted 4-6 membered heterocyclic alkyl rings, thereby forming a spirocyclic ring system.

[0167] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a C that does not include any additional cyclic heterogeneous moiety. 4-8 Heterocyclic alkyl groups.

[0168] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, C forms a monocyclic or fused bicyclic ring. 4-8 Heterocyclic alkyl groups.

[0169] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a single-ring C 6-8 Heterocyclic alkyl groups.

[0170] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a bicyclic C 6-8 Heterocyclic alkyl groups.

[0171] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, they form fused C 4-8 Heterocyclic alkyl groups.

[0172] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms an unsubstituted C 4-8 Heterocyclic alkyl groups.

[0173] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, they form unsubstituted and monocyclic or fused bicyclic C atoms. 4-8 Heterocyclic alkyl groups.

[0174] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms an unsubstituted and monocyclic C.4-8 Heterocyclic alkyl groups.

[0175] In the embodiment, R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms an unsubstituted and fused bicyclic C 4-8 Heterocyclic alkyl groups.

[0176] In the embodiment, R 1 Independently selected from hydrogen, or optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Halogenated alkyl groups, optionally substituted C 3-8 cycloalkyl, optionally substituted C 4-14 Alkylene cycloalkyl, optionally substituted C3-C8 heterocyclic alkyl, optionally substituted C4-C 14 alkylene heterocyclic alkyl, optionally substituted C 6-12 aryl, optionally substituted C 7-18 alkylene aryl, optionally substituted C 5-10 Heteroaryl and optionally substituted C 6-16 alkylene heteroaryl, and R 2 Independently selected from the arbitrarily substituted C 3-8 cycloalkyl, optionally substituted C 4-14 Alkylene cycloalkyl, optionally substituted C3-C8 heterocyclic alkyl, optionally substituted C4-C 14 alkylene heterocyclic alkyl, optionally substituted C 6-12 aryl, optionally substituted C 7-18 alkylene aryl, optionally substituted C 5-10 Heteroaryl and optionally substituted C 6-16 alkylene heteroaryl, Alternatively, R 1 and R 2 Together with the atoms they are attached, they form optionally substituted C atoms. 3-8 Heterocyclic alkyl groups, the optionally substituted C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 .

[0177] In the embodiment, R 2 C is an optional substitute 1-6 Halogenated alkyl groups.

[0178] In the embodiment, R 1 It is independently selected from hydrogen, methyl, ethyl, isopropyl and cyclopropyl.

[0179] In the embodiment, R 2It is selected from hydrogen, trifluoroisopropyl, cyclopropyl, difluorocyclopropyl, cyclobutyl, methylenecyclopropyl, 1-cyclopropyl-ethyl, benzyl, methoxybenzyl and fluorobenzyl.

[0180] In the embodiment, R 1 and R 2 Together with the nitrogen it is attached to, it forms any of the following: -NH2、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0181] In the embodiment, R 1 and R 2 Together with the nitrogen it is attached to, it forms any of the following: -NH2、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0182] In some embodiments, R 1 and R 2 Together with the nitrogen it is attached to, it forms any of the following: , and .

[0183] In the embodiment, R 3 Independently selected from hydrogen and C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7 Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; In the embodiment, R 3 Independently selected from hydrogen and optionally substituted C 1-6 alkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form an optionally substituted C 3-12 Heterocyclic alkyl groups.

[0184] In some embodiments, R 3 It is hydrogen.

[0185] In some embodiments, R 3 C is an optional replacement 1-6 alkyl.

[0186] In some embodiments, R 1 For H, R 2 For H, and R 3 C is an optional replacement 1-6 Alkyl group. In some embodiments, R 1 For H, R 2 For H, and R 3 C is an optional replacement 1-4 Alkyl group. In some embodiments, R 1 For H, R 2 For H, and R 3 C is an optional replacement 1-3 alkyl.

[0187] In the embodiment, R 3 and R 2 The atoms it is attached to combine to form optionally substituted C 3-12 Heterocyclic alkyl groups. In these embodiments, compounds of formula (I) may be provided as compounds of formula (IV): (IV) in: R 1 and R 9 As defined in any embodiment or aspect thereof; and G is an optional substitution of C 3-12 Heterocyclic alkyl, preferably C 4-6 Heterocyclic alkyl groups. The "C" of the heterocyclic alkyl moiety. x-y The reference to “G” includes the nitrogen atom depicted within the atomic count. Therefore, G can be alternatively defined as a 3-12 membered heterocyclic alkyl group, including the depicted nitrogen atom and optionally one or two additional cyclic heteroatoms selected from the following: O, S, S(O), SO2, N, NH and NCH3, wherein the remaining cyclic atoms are carbon atoms.

[0188] R 9 In the embodiment, R 9 Independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; In the embodiment, R 9 Independently selected from halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 132. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; In the embodiment, R 9 Independently selected from halogens, CN, -OH, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups, The C 1-6 Halogenated alkyl groups, the C 1-6 alkoxy groups and the C 1-6 The haloalkoxy group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 .

[0189] In the embodiment, R 9 Independently selected from halogens, -OH, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups, The C 1-6 Halogenated alkyl groups, the C 1-6 alkoxy groups and the C 1-6 The haloalkoxy group is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, CO2R 13C(O)N(R) 13 2. OR 13 、N(R 13 2. NO2, SR 13 and SO2R 13 .

[0190] In the embodiment, R 9 Selected from halogens, CN, -OH, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 Halogenated alkyl groups.

[0191] In some embodiments, R 9 Selected from halogens, -OH, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 Halogenated alkyl groups.

[0192] In the embodiment, R 9 Selected from fluorine, chlorine, bromine, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0193] In the embodiment, R 9 Selected from fluorine, chlorine, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0194] In the embodiment, R 9 It is fluorine.

[0195] In the embodiment, R 9 It is fluorine, and R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a C that does not include any additional cyclic heterogeneous moiety. 4-8 Heterocyclic alkyl groups.

[0196] In the embodiment, R 9 It is fluorine, and R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a monocyclic or fused C 4-8 Heterocyclic alkyl groups.

[0197] In the embodiment, R 9 It is fluorine, and R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms a single-ring C 4-8 Heterocyclic alkyl groups.

[0198] In the embodiment, R 9 It is fluorine, and R 1 and R 2 Together with the nitrogen atom to which it is attached, they form unsubstituted and monocyclic or fused C atoms. 4-8Heterocyclic alkyl groups.

[0199] In the embodiment, R 9 It is fluorine, and R 1 and R 2 Together with the nitrogen atom to which it is attached, it forms an unsubstituted and monocyclic C. 4-8 Heterocyclic alkyl groups.

[0200] In the embodiment, R 9 It is chlorine.

[0201] In the embodiment, R 9 It is bromine.

[0202] In the embodiment, R 9 For CN.

[0203] In the embodiment, R 9 It is a methoxy group.

[0204] In the embodiment, R 9 It is trifluoromethoxy.

[0205] R 8 and R 10 In the embodiment, R 8 It is hydrogen.

[0206] In the embodiment, R 10 It is hydrogen.

[0207] In the embodiment, R 8 and R 10 It is hydrogen.

[0208] In the embodiment, R 8 and R 10 It is hydrogen, and R 9 It is not hydrogen.

[0209] In the embodiment, R 8 and R 10 It is hydrogen, and R 9 Selected from fluorine, chlorine, bromine, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

[0210] In the embodiment, R 8 and R 10 It is hydrogen, and R 9 It is not fluorine.

[0211] Another formula of the compound In the examples, the compounds of formula (I) are selected from compounds S1-S75 or their pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs or prodrugs.

[0212] In the examples, the compounds of formula (I) are selected from compounds S1-S42 or their pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs or prodrugs.

[0213] In the examples, the compounds of formula (I) are selected from compounds S1-S28 and S30-S75 or their pharmaceutically acceptable salts, solvates, tautomers, N-oxides, stereoisomers, metabolites, polymorphs or prodrugs.

[0214] In some embodiments, the compound of formula (I) is selected from compounds 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.

[0215] compound form In the case of solid compounds, those skilled in the art will understand that the compounds, agents, and salts of the present invention may exist in different crystalline or polymorphic forms, all of which are intended to fall within the scope and specific formulation of the present invention.

[0216] This invention includes all crystalline forms of compounds of formula (I), including anhydrous crystalline forms, hydrates, solvates, and mixed solvates. All polymorphs are within the scope of this invention if any of these crystalline forms exhibit polymorphism.

[0217] Formula (I) is intended to cover compounds in both solvated and unsolvated forms (where applicable). Thus, Formula (I) includes compounds having an indicative structure, including hydrated or solvated forms, as well as unhydrated and unsolvated forms.

[0218] Compounds of formula (I) or their salts, tautomers, N-oxides, polymorphs, or prodrugs may be provided in the form of solvates. The solvates contain stoichiometric or non-stoichiometric amounts of solvent and may be formed during crystallization using pharmaceutically acceptable solvents such as water, alcohols (e.g., methanol, ethanol, or isopropanol), DMSO, acetonitrile, dimethylformamide (DMF), acetic acid, etc., by non-covalent bonding or by occupying pores in the lattice. When the solvent is water, a hydrate is formed; when the solvent is an alcohol, an alcohol is formed. Solvates of the compounds of the present invention can be conveniently prepared or formed during the processes described herein. Generally, for the purposes of the present invention, the solvated form is considered equivalent to the non-solvated form.

[0219] Basic nitrogen-containing groups can be quaternized using the following reagents: C 1-6Alkyl halides, such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkyl sulfates, such as dimethyl sulfate and diethyl sulfate; etc.

[0220] Nitrogen-containing groups can also be oxidized to form N-oxides.

[0221] Compounds of formula (I) or their salts, tautomers, N-oxides, solvates, and / or prodrugs that form crystalline solids may exhibit polymorphism. All polymorphic forms of the compounds, salts, tautomers, N-oxides, solvates, and / or prodrugs are within the scope of this invention.

[0222] Compounds of formula (I) can exhibit tautomerism. Tautomers are two interchangeable forms of a molecule that are normally present in equilibrium. Any tautomer of a compound of formula (I) should be understood to be within the scope of this invention.

[0223] Compounds of formula (I) may contain one or more stereocenters. All stereoisomers of compounds of formula (I) are within the scope of this invention. Stereoisomers include enantiomers, diastereomers, geometric isomers (E- and Z-alkene forms and cis- and trans-substituted modes), and trans-restricted isomers. In some embodiments, the compound is a stereoisomerically enriched form of the compound of formula (I) at any stereocenter. The enrichment of the compound in one stereoisomer may be at least about 60%, 70%, 80%, 90%, 95%, 98%, or 99% of the enrichment in another stereoisomer.

[0224] Compounds of formula (I) or their salts, tautomers, solvates, N-oxides, and / or stereoisomers can be isotopically enriched using one or more isotopes of the atoms present in the compound. For example, the compound can be enriched using one or more trace isotopes of the following: 2 H, 3 H, 13 C 14 C 15 N、 17 O and / or 18 F, preferably 2 H. When the abundance of an isotope is greater than its natural abundance, it can be considered enriched.

[0225] A "prodrug" is a compound that may not fully meet the structural requirements of the compounds provided herein, but is modified in vivo to produce a compound of formula (I) provided herein after administration to a subject or patient. For example, a prodrug can be an acylated derivative of a compound provided herein. Prodrugs include compounds in which a hydroxyl, carboxyl, amino, or thiol group is bonded to any group that, upon administration to a mammalian subject, is cleaved to form a free hydroxyl, carboxyl, amino, or thiol 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 can be prepared by modifying the functional groups present in the compound in such a way that the modified compound is cleaved in vivo to produce the parent compound.

[0226] The prodrug comprises a compound in which a polypeptide chain of one or more amino acid residues (e.g., two, three, or four) is covalently linked to the free amino and amine groups of a compound of formula (I). The amino acid residues include 20 naturally occurring amino acids, typically represented by three-letter symbols, and also include 4-hydroxyproline, hydroxylysine, demosine, isodemosine, 3-methylhistidine, valine, β-alanine, γ-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine, and methionine sulfone. The prodrug also includes compounds in which carbonates, carbamates, amides, and alkyl esters are covalently bonded to substituents of formula (I) via a carbonyl carbon prodrug side chain.

[0227] Composition, formulation and application patterns Compounds of formula (I) may be administered alone or as a pharmaceutical composition. In practice, compounds of formula (I) are typically administered as a pharmaceutical composition, i.e., as a mixture with at least one pharmaceutically acceptable excipient. The proportion and properties of any pharmaceutically acceptable excipient are determined by the characteristics of the selected compound, the selected route of administration, and standard pharmaceutical practice.

[0228] 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.

[0229] The pharmaceutical compositions disclosed herein 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, flavoring agents and diluents, emulsifiers, suspending agents, solvents, fillers, thickeners, buffers, delivery mediators, diluents, excipients and / or adjuvants. For example, suitable mediators may be water for injection, physiological saline solution or artificial perilymph, possibly supplemented with other materials commonly found in compositions intended for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are other exemplary mediators.

[0230] The pharmaceutical compositions disclosed herein further comprise pharmaceutically acceptable carriers, as used herein, including any and all solvents, diluents or other liquid media, dispersants or suspending agents, surfactants, isotonic agents, thickeners or emulsifiers, preservatives, solid binders, lubricants, etc., suitable for the desired particular dosage form. Remington's Pharmaceutical Sciences, 16th edition, EWMartin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers for formulating pharmaceutical compositions and known techniques for their preparation. Unless any conventional carrier medium is incompatible with the compounds of the present invention, such as by producing any undesirable biological effects or otherwise interacting in a harmful manner with any other component of the pharmaceutical composition, its use is contemplated within the scope of this disclosure. Based on the coagulator's judgment, some examples of materials that can serve as pharmaceutically acceptable carriers include, but are not limited to, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; powdered astragalus; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; ethylene glycol such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol and phosphate buffer solutions; and other non-toxic, compatible lubricants such as sodium dodecyl sulfate and magnesium stearate, as well as colorants, release agents, coating agents, sweeteners, flavorings, and flavorings, preservatives, and antioxidants may also be present in the composition.

[0231] Each dosage unit is preferably provided in discrete doses as tablets, capsules, lozenges, sugar-coated pills, gels, or other types of solid formulations. Capsules may encapsulate powders, liquids, or gels. Solid formulations may be swallowed or may be of a suckable or chewable type (fragile or gum-like). The invention envisions dosage unit holding devices other than blister packs; for example, bottles, tubes, cans, bags, etc. Dosage 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 conventional excipients for suckable or chewable formulations.

[0232] Compounds of formula (I) can be administered in any form and by any route that makes the compound bioavailable.

[0233] The compositions described herein can be applied systemically or directly to the site of symptoms or disease.

[0234] The compositions described herein can be formulated from compounds according to formula (I) for any suitable route of administration, including, for example, oral, rectal, nasal, vaginal, topical (including percutaneous, buccal, ocular, and sublingual), parenteral (including subcutaneous, intraperitoneal, intradermal, intravascular (e.g., intravenous), intramuscular, spinal, intracranial, intrathecal, intraocular, periorbital, intraorbital, intrasynovial, and intraperitoneal injections, intracisional injections, and any other similar injection or infusion techniques), inhalation, blowing, infusion, or implantation techniques (e.g., sterile injectable water or non-aqueous solutions or suspensions). In some embodiments, the compositions described herein can be administered orally, nasally, intravenously, intramuscularly, topically, subcutaneously, rectally, vaginally, or via urethral application.

[0235] Compositions intended for oral use may further comprise one or more components, such as sweeteners, flavoring agents, coloring agents, and / or preservatives, to provide an appealing and palatable formulation. Tablets contain a mixture of the active ingredient and physiologically acceptable excipients suitable for tablet preparation. Such excipients include, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulating and disintegrants (such as corn starch or alginic acid); binders (such as starch, gelatin, or gum arabic); and lubricants such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated, or they may be coated using known techniques to delay disintegration and absorption in the gastrointestinal tract, thereby providing a prolonged effect over a longer period. For example, delaying materials such as glyceryl monostearate or glyceryl distearate may be used.

[0236] Formulations for oral use may also be presented in the form of hard gelatin capsules or soft gelatin capsules, in which the active ingredient is mixed with an inert solid diluent (such as calcium carbonate, calcium phosphate, or kaolin), and in which the active ingredient is mixed with an aqueous or oil medium (e.g., peanut oil, liquid paraffin, or olive oil).

[0237] Oily suspensions can be formulated by suspending the active ingredient in vegetable oils (such as peanut oil, olive oil, sesame oil, or coconut oil) or mineral oils (liquid paraffin). Oily suspensions may contain thickeners such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners and / or flavorings, such as those described above, can be added to provide a palatable oral formulation. Such suspensions can be preserved by adding antioxidants such as ascorbic acid.

[0238] Dispersible powders and granules suitable for preparing aqueous suspensions by adding water provide mixtures of active ingredients with dispersants or wetting agents, suspending agents, and one or more preservatives. Suitable dispersants or wetting agents and suspending agents are illustrated by those already mentioned above. Other excipients, such as sweeteners, flavoring agents, and coloring agents, may also be present.

[0239] Pharmaceutical compositions may also be in the form of oil-in-water emulsions. The oil phase may be vegetable oil (such as olive oil or peanut oil), mineral oil (such as liquid paraffin), or mixtures thereof. Suitable emulsifiers include naturally occurring gums (such as gum arabic and tragacanth), naturally occurring phospholipids (such as soybean lecithin), and esters or metaesters derived from fatty acids and hexitols, acid anhydrides (such as sorbitan monooleate), and condensation products of metaesters derived from fatty acids and hexitols with ethylene oxide (such as polyoxyethylene sorbitan monooleate). The emulsion may also contain one or more sweeteners and / or flavoring agents.

[0240] Syrups and elixirs can be formulated with sweeteners such as glycerin, propylene glycol, sorbitol, or sucrose. Such formulations may also contain one or more modifiers, preservatives, flavoring agents, and / or coloring agents.

[0241] The composition may further include one or more components suitable for improving the stability or effectiveness of the applied formulation, such as stabilizers, suspending agents, emulsifiers, viscosity modifiers, gelling agents, preservatives, antioxidants, skin penetration enhancers, moisturizers, 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 hydroxymethyl cellulose or gelatin microcapsules, liposomes, albumin microspheres, microemulsions, nanoparticles, or nanocapsules.

[0242] Preservatives include, but are not limited to, antibacterial 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 moisturizers 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 neopentyl ester, and mineral oil. Suitable fragrances and pigments include, but are not limited to, FD&C Red 40 and FD&C Yellow 5. Other suitable additional ingredients that may be included in topical formulations include, but are not limited to, abrasives, absorbents, anti-caking agents, antifoaming agents, antistatic agents, astringents (such as witch hazel), alcohols and herbal extracts (such as chamomile extract), binders / excipients, buffers, chelating agents, film-forming agents, conditioning agents, propellants, emulsifiers, pH adjusters, and protectants.

[0243] 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, liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers, and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethylformamide, oils (specifically, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerin, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof. In addition to inert diluents, oral compositions may also include adjuvants such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents, and aromatizers.

[0244] Injectable formulations (e.g., sterile injectable aqueous or oily suspensions) can be formulated using known techniques, employing suitable dispersants or wetting agents and suspending agents. Sterile injectable formulations can also be sterile injectable solutions, suspensions, or emulsions in the form of non-toxic, parenteral-acceptable diluents or solvents, such as solutions in the form of 1,3-butanediol. Acceptable mediators and solvents that can be used are water, Ringer's solution, USP, and isotonic sodium chloride solution. Additionally, sterile fixed oils are routinely used as solvents or suspension media. For this purpose, any mild fixed oil can be used, including synthetic monoglycerides or diglycerides. Furthermore, fatty acids, such as oleic acid, are used to prepare injectable formulations.

[0245] Injectable formulations can be sterilized, for example, by filtering through a bacterial trap or by incorporating a sterilizing agent in the form of a sterile solid composition, which can be dissolved or dispersed in sterile water or other sterile injectable media only before use.

[0246] Pharmaceutical compositions can be formulated as inhaled formulations, including sprays, nebulizers, or aerosols. For inhaled formulations, the compositions or combinations provided herein can be delivered by 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 are respiratory-operated inhalers, multi-dose dry powder inhalers, and aerosol nebulizers. Aerosol formulations used in the methods of this subject typically include a propellant, a surfactant, and a cosolvent, and can be filled into a conventional aerosol container closed by a suitable metering valve.

[0247] Inhalation compositions may comprise liquid or powder compositions containing an active ingredient suitable for nebulization and intrabronchial use, or aerosol compositions administered via a metered-dose aerosol unit. Suitable liquid compositions contain the active ingredient in an aqueous, pharmaceutically acceptable inhalation solvent, such as isotonic saline or antibacterial water. The solution is administered via a pump or squeeze-operated nebulizer dispenser or any other conventional method for enabling or allowing the necessary dose of the liquid composition to be inhaled into the patient's lungs. Where the carrier is a suitable liquid formulation for administration (e.g., nasal spray or nasal drops) comprising an aqueous or oily solution of the active ingredient.

[0248] Compositions suitable for rectal administration are preferably presented in the form of unit-dose suppositories. These unit-dose suppositories can be prepared by dispersing the active ingredient at least partially in one or more lipophilic bases and then shaping the mixture.

[0249] Pharmaceutical compositions can be formulated as sustained-release formulations, such as capsules that produce a slow release of the active ingredient upon administration. Such formulations are typically prepared using well-known techniques and can be administered, for example, orally, rectally, or subcutaneously, or by implantation at the desired target site. The carrier used in such formulations is biocompatible and may also be biodegradable. Preferably, the formulation provides a relatively constant level of active ingredient release. The amount of active ingredient contained in the sustained-release formulation depends, for example, on the implantation site, the release rate and the expected duration of release, and the nature of the condition to be treated.

[0250] Those skilled in the art can readily select the appropriate form and route of administration based on the specific properties of the selected compound, the disease or symptom to be treated, the stage of the disease or symptom, and other relevant circumstances.

[0251] It should be understood that the specific dosage level for any particular patient will depend on a wide range of factors, including the activity of the specific compound used, age, weight, health status, sex, diet, time of administration, route of administration, frequency of administration and excretion rate, drug combination (i.e., other drugs used to treat the patient) and the severity of the specific condition being treated.

[0252] The phrase “therapeutic effective amount” generally refers to the amount of one or more active ingredients of the present invention that (i) treat a particular disease, condition or symptom, (ii) reduce, improve or eliminate one or more signs or symptoms of a particular disease, condition or symptom, or (iii) delay the onset of one or more signs or symptoms of a particular disease, condition or symptom described herein.

[0253] Typically, therapeutically effective doses are formulated to contain at least about 0.1% to about 50% or more, and all combinations and sub-combinations thereof, at concentrations (by weight). Compositions may be formulated to contain one or more active ingredients described herein at concentrations from about 0.1% to less than about 50%, such as about 49%, 48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, or 40%, wherein the concentration is greater than about 0.1% (e.g., about 0.2%, 0.3%, 0.4%, or 0.5%) to less than about 40% (e.g., about 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, or 30%). Exemplary compositions may contain concentrations from about 0.5% to less than about 30%, such as about 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, or 20%, wherein the concentration is greater than about 0.5% (e.g., about 0.6%, 0.7%, 0.8%, 0.9%, or 1%) to less than about 20% (e.g., about 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, or 10%). Compositions may contain greater than about 1% (e.g., about 2%) to less than about 10% (e.g., about 9% or 8%), including concentrations greater than about 2% (e.g., about 3% or 4%) to less than about 8% (e.g., about 7% or 6%). The active agent may be present, for example, at a concentration of about 5%. In all cases, the amount can be adjusted to compensate for variations in the amount of active ingredient actually delivered to the treated cells or tissues.

[0254] The frequency of application can be once daily, twice daily, three times daily, or four times daily. The treatment period can be the duration of the detectable disease.

[0255] In some embodiments, the pharmaceutical composition comprises a compound according to any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug, additional therapeutic agent, and pharmaceutically acceptable excipient thereof.

[0256] The additional agent may be any suitable agent described herein. In some embodiments, the additional agent is a psychoactive drug, including the psychoactive drugs described herein. In some embodiments, the additional agent may be used to treat a disease, condition, or symptom by activating serotonin receptors, including the serotonin receptors described herein. In some embodiments, the additional agent is selected from any of the following, including the agents described herein: agents for mental illness and / or neuropsychiatric symptoms; agents for psychosis 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.

[0257] application This disclosure provides methods for using compounds and compositions of formula (I) described in any of the preceding paragraphs. This disclosure also provides methods for delivering a compound or composition of formula (I) of this disclosure (e.g., an effective amount of the compound or composition) to a subject in need.

[0258] In another aspect, this disclosure provides a method for treating a disease in a subject in need, the method comprising administering to the subject in need an effective amount (e.g., a therapeutically effective amount) of a compound or composition of this disclosure (e.g., a pharmaceutical composition).

[0259] In another aspect, this disclosure provides a method for preventing disease in a subject in need, the method 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 this disclosure (e.g., a pharmaceutical composition).

[0260] In another aspect, this document provides for the use of compounds or compositions of formula (I) of this disclosure in the preparation of medicaments for use in the methods of this disclosure (e.g., methods for delivering an active agent to a subject in need, methods for treating a disease in a subject in need, methods for preventing a disease in a subject in need).

[0261] In another aspect, this document provides for the use of compounds or compositions of formula (I) of this disclosure in the methods of this disclosure (e.g., methods for delivering an active agent to a subject in need, methods for treating a disease in a subject in need, methods for preventing a disease in a subject in need).

[0262] In some embodiments, the effective amount can effectively treat the disease. In some embodiments, the effective amount can effectively prevent the disease.

[0263] In another aspect, this disclosure provides a method for treating a disease, condition, or symptom by activating a serotonin receptor, the method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein.

[0264] In another aspect, this disclosure provides a method for preventing disease, condition or symptom by activating serotonin receptors, the method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein.

[0265] In another aspect, this disclosure provides a method for treating a disease, condition, or symptom by activating a serotonin receptor, the method comprising administering to a subject in need a combination of a compound or pharmaceutical composition of formula (I) as described herein with another known pharmaceutical agent that can be used to treat a disease, condition, or symptom by activating a serotonin receptor. The other known pharmaceutical agent that can be used to treat a disease, condition, or symptom by activating a serotonin receptor can be any suitable agent known in the art, including the agents described herein.

[0266] In another aspect, this disclosure provides a method for preventing disease, condition, or symptom by activating serotonin receptors, the method comprising administering to a subject in need a combination of a compound or pharmaceutical composition of formula (I) as described herein with another known agent that can be used to prevent disease, condition, or symptom by activating serotonin receptors.

[0267] In some embodiments, the serotonin receptor is 5-HT. 2A .

[0268] In some embodiments, the serotonin receptor is 5-HT. 2A and 5-HT 2C One or more of these. Alternatively or alternatively, in some embodiments, the serotonin receptor is not 5-HT. 2B .

[0269] In some embodiments, the compounds of formula (I) of this disclosure are effective against 5-HT. 2A The receptor selectivity is superior to that for 5-HT 2C receptors and 5-HT 2B The selectivity for one or both of the receptors is preferably superior to that for 5-HT. 2B Receptor selectivity. In some embodiments, the compound of formula (I) is effective against 5-HT. 2C The receptor selectivity is superior to that for 5-HT 2A receptors and 5-HT 2B The selectivity for one or both of the receptors is preferably superior to that for 5-HT. 2B Receptor selectivity. In some embodiments, the compound of formula (I) is effective against 5-HT. 2A receptors and 5-HT 2C The receptor selectivity is superior to that for 5-HT 2B Receptor selectivity.

[0270] In some embodiments, the compounds of formula (I) of this disclosure exhibit the activity against 5-HT as determined by assays described herein (e.g., calcium flux activity assays, such as measurements of changes in intracellular calcium). 2A EC of receptors 50Values ​​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. In some embodiments, compounds of formula (I) exhibit the activity against 5-HT as determined by calcium flux activity or IP1 accumulation assay. 2A EC of receptors 50 Values ​​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, 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 about 300 nM, less than about 200 nM, or less than about 100 nM, or any equivalent unit of measurement (e.g., mol / L).

[0271] In some embodiments, the compounds of formula (I) of this disclosure exhibit the activity against 5-HT as determined by assays described herein (e.g., calcium flux activity assays, such as measurements of changes in intracellular calcium). 2C EC of receptors 50 Values ​​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. In some embodiments, compounds of formula (I) exhibit the activity against 5-HT as determined by calcium flux assay. 2C EC of receptors 50Values ​​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, 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 about 300 nM, less than about 200 nM, or less than about 100 nM, or any equivalent unit of measurement (e.g., mol / L).

[0272] In some embodiments, the compounds of formula (I) of this disclosure exhibit the activity against 5-HT as determined by assays described herein (e.g., calcium flux activity assays, such as measurements of changes in intracellular calcium). 2B EC of receptors 50 Values ​​greater than approximately 1 µM, greater than approximately 10 µM, or greater than approximately 100 µM.

[0273] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is a mental illness or neuropsychiatric symptom. Therefore, this application also includes a method of treating a mental illness or neuropsychiatric symptom, the method comprising administering a compound or composition of formula (I) as described herein to a subject in need. This application also includes the use of a compound of formula (I) of this disclosure for treating a mental illness or neuropsychiatric symptom and the use of a compound of formula (I) of this disclosure for preparing a medicament for treating a mental illness or neuropsychiatric symptom. This application further includes a compound of formula (I) of this disclosure for treating a mental illness or neuropsychiatric symptom.

[0274] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is a mental illness or neuropsychiatric symptom, and the compound of formula (I) of this disclosure is administered in combination with one or more additional agents for mental illness or neuropsychiatric symptom. The one or more additional agents for mental illness or neuropsychiatric symptom can be any suitable agent known in the art, including those described herein. In some embodiments, the additional agents for mental illness or neuropsychiatric symptom 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); anti-anxiety medications, including benzodiazepines such as alprazolam; and agents for addiction disorders, such as agents for alcohol addiction (e.g., disulfiram). Lfiram), medications for nicotine dependence (e.g., varenicline), and medications for opioid disorders (e.g., methadone, buprenorphine, naloxone, and long-acting buprenorphine injection); mood stabilizers such as lithium; and anticonvulsants such as carbamazepine, divalproex, lamotrigine, gabapentin, and topiramate.

[0275] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is neurodegeneration. Therefore, this application also includes a method of treating neurodegeneration, the method comprising administering a compound or composition of formula (I) as described herein to a subject in need. This application also includes use of a compound of formula (I) of this disclosure for treating neurodegeneration and use of a compound of formula (I) of this disclosure for preparing a medicament for treating neurodegeneration. This application further includes a compound of formula (I) of this disclosure for treating neurodegeneration. In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is a reduction in brain-derived neurotrophic factor (BDNF), activation of mammalian target of rapamycin (mTOR), and / or inflammation.

[0276] In some embodiments, diseases, conditions, or symptoms treated by activating serotonin receptors include cognitive impairment; ischemia, including stroke; neurodegeneration; refractory substance use disorder; sleep disorders; pain, such as social pain, acute pain, cancer pain, chronic pain, breakthrough pain, bone pain, soft tissue pain, neuralgia, referred pain, phantom limb pain, neuropathic pain, cluster headache, and migraine; obesity and eating disorders; epilepsy and paroxysmal symptoms; neuronal cell death; excitotoxic cell death; or combinations thereof.

[0277] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is psychosis or psychotic symptoms. Therefore, this application also includes a method of treating psychosis or psychotic symptoms, the method comprising administering a compound or composition of formula (I) as described herein to a subject in need. This application also includes the use of a compound of formula (I) of this disclosure for treating psychosis or psychotic symptoms and the use of a compound of formula (I) of this disclosure for preparing a medicament for treating psychosis or psychotic symptoms. This application further includes a compound of formula (I) of this disclosure for treating psychosis or psychotic symptoms.

[0278] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is psychosis or psychotic symptoms, and the compound of formula (I) of this disclosure is administered in combination with one or more additional agents for psychosis or psychotic symptoms. The one or more additional agents for psychosis or psychotic symptoms can be any suitable agent known in the art, including those described herein. In some embodiments, the additional agents for psychosis or psychotic symptoms are selected typical and atypical antipsychotics.Typical antipsychotic drugs can be selected from promazine, acetophenazine, benperidol, bromperidol, butaperazine, carfenazine, chlorproethazine, chlorpromazine, chlorprothixene, clopenthixol, cyamemazine, and diazepam. xyrazine, droperidol, fluanisone, flupentixol, fluphenazine, fluspirilene, haloperidol, levomepromazine, lenperone, loxapine, mesoridazine, metitepine, molindone, moperone One), oxypertine, oxyprotepine, penfluridol, perazine, periciazine, perphenazine, pimozide, pipamperone, piperacetazine, pipotiazine, prochlorperazine, promazine, prothiamine pendyl), spirerone, sulforidazine, thiopropazate, thioproperazine, thioridazine, thiothixene, timiperone, trifluoperazine, trifluperidol, triflupromazine, and zuclopenthixol, as well as combinations thereof.Atypical antipsychotics can be selected from amoxapine, amisulpride, aripiprazole, asenapine, blonanserin, brexpiprazole, cariprazine, carpipramine, clocapramine, colotepine, clotiapine, clozapine, iloperidone, levosulpiride, lurasidone, and mepiquat. Melperone, mosapramine, nemonapride, olanzapine, paliperidone, perospirone, quetiapine, remoxipride, reserpine, risperidone, sertindole, sulpiride, sultopride, tiapride, veralipride, ziprasidone, and zotepine, as well as combinations thereof.

[0279] In some embodiments, administration of a therapeutically effective amount of the compound of formula (I) of this disclosure to the subject in need does not worsen psychosis or psychotic symptoms (such as, but not limited to, hallucinations and delusions). In some embodiments, administration of a therapeutically effective amount of the compound of formula (I) to the subject in need improves psychosis or psychotic symptoms (such as, but not limited to, hallucinations and delusions). In some embodiments, administration of a therapeutically effective amount of the compound of formula (I) to the subject in need improves psychosis or psychotic symptoms.

[0280] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is a central nervous system (CNS) disease, condition, or symptom and / or a neurological disease, condition, or symptom. Therefore, this application also includes a method of treating a CNS disease, condition, or symptom and / or a neurological disease, condition, or symptom, the method comprising administering a therapeutically effective amount of a compound or composition of formula (I) of this disclosure to a subject in need. This application also includes the use of a compound of formula (I) of this disclosure for treating a CNS disease, condition, or symptom and / or a neurological disease, condition, or symptom, and the use of a compound of formula (I) of this disclosure for preparing a medicament for treating a CNS disease, condition, or symptom and / or a neurological disease, condition, or symptom. This application further includes a compound of formula (I) of this disclosure for treating a CNS disease, condition, or symptom and / or a neurological disease, condition, or symptom.

[0281] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is a central nervous system (CNS) disease, condition, or symptom and / or a neurological disease, condition, or symptom, and the compound of formula (I) of this disclosure is administered in combination with one or more other agents for central nervous system (CNS) diseases, conditions, or symptoms and / or neurological diseases, conditions, or symptoms. The one or more other agents for central nervous system (CNS) diseases, conditions, or symptoms and / or neurological diseases, conditions, or symptoms can be any suitable agent known in the art, including the agents described herein. In some embodiments, additional agents for central nervous system (CNS) diseases, conditions or symptoms and / or neurological diseases, conditions or symptoms are selected from lithium, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, clozapine, sodium valproate, lamotrigine, valproic acid, carbamazepine, topiramate, levomilnacipran, duloxetine, venlafaxine, citalopram, fluvoxamine, escitalopram. Am, fluoxetine, paroxetine, sertraline, clomipramine, amitriptyline, desipramine, imipramine, nortriptyline, phenelzine, tranylcypromine, diazepam, alprazolam, clonazepam, or any combination thereof. Non-limiting examples of standard care for depression include sertraline, fluoxetine, escitalopram, venlafaxine, or aripiprazole. Non-limiting examples of standard care for depression include citalopram, escitalopram, fluoxetine, paroxetine, diazepam, or sertraline.

[0282] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is selected from attention deficit hyperactivity disorder (ADHD) and attention deficit disorder, and combinations thereof. Therefore, this application also includes a method of treating ADHD and / or attention deficit disorder, the method comprising administering a compound or composition of formula (I) as described herein to a subject in need. This application also includes the use of a compound of formula (I) of this disclosure for treating ADHD and / or attention deficit disorder, and the use of a compound of formula (I) of this disclosure for preparing a medicament for treating ADHD and / or attention deficit disorder. This application further includes a compound of formula (I) of this disclosure for treating ADHD and / or attention deficit disorder.

[0283] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is attention deficit hyperactivity disorder (ADHD) and / or attention deficit disorder, and combinations thereof, and the compound of formula (I) of this disclosure is administered in combination with one or more additional agents for ADHD and / or attention deficit disorder, and combinations thereof. The one or more additional agents for ADHD and / or attention deficit disorder can be any suitable agent known in the art, including those described herein. In some embodiments, the additional agents for ADHD and / or attention deficit disorder, and combinations thereof are selected from methylphenidate, dexamphetamine, lisdexamfetine, atoxetine, and amphetamines, and combinations thereof.

[0284] In some embodiments, the diseases, conditions, or symptoms treated by activating serotonin receptors are selected from dementia and Alzheimer's disease, and combinations thereof. Therefore, this application also includes a method of treating dementia and / or Alzheimer's disease, the method comprising administering a compound or composition of formula (I) as described herein to a subject in need. This application also includes the use of a compound of formula (I) of this disclosure for treating dementia and / or Alzheimer's disease and the use of a compound of formula (I) of this disclosure for preparing a medicament for treating dementia and / or Alzheimer's disease. This application further includes a compound of formula (I) of this disclosure for treating dementia and / or Alzheimer's disease.

[0285] In some embodiments, the disease, condition, or symptom treated by activating serotonin receptors is dementia or Alzheimer's disease, and the compound of formula (I) of this disclosure is administered in combination with one or more other agents for dementia or Alzheimer's disease. The one or more other agents for dementia or Alzheimer's disease may be any suitable agent known in the art, including those described herein. In some embodiments, the other agents for dementia and Alzheimer's disease are selected from acetylcholinesterase inhibitors, NMDA antagonists, and nicotine agonists. The acetylcholinesterase inhibitors may be selected from donepezil, galantamine, rivastigmine, phenserine, and combinations thereof. The NMDA antagonists may be selected from MK-801, ketamine, phencyclidine, and memantine, and combinations thereof. Nicotine agonists may be selected from nicotine, nicotinic acid, nicotine α7 agonists or α2 β4 agonists or combinations thereof.

[0286] In another aspect, this disclosure provides a method for treating a mental illness, the method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein. In yet another aspect, this disclosure provides a method for preventing a mental illness, the method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein. The mental illness may be a neuropsychiatric symptom.

[0287] In some embodiments, mental illnesses are selected from anxiety disorders such as generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobias; depression such as feelings of hopelessness, loss of interest, fatigue, and suicidal ideation; mood disorders such as depression, bipolar disorder, cancer-related depression, anxiety, and cyclical mood disorders; mental disorders such as hallucinations, delusions, mania, schizophrenia, schizoaffective disorder, and schizophrenia-like disorders; impulse control and addiction disorders such as pyrokinesis, kleptomania, and compulsive gambling; alcohol addiction; and drug addiction such as opioid addiction / dependence, nicotine dependence, and cocaine addiction. Due to dependence, marijuana abuse, etc.; smoking cessation; personality disorders, such as antisocial personality disorder, aggressive personality disorder, obsessive-compulsive personality disorder, and paranoid personality disorder; obsessive-compulsive disorder (OCD), such as thoughts or fears that cause the subject to perform certain rituals or routines; post-traumatic stress disorder (PTSD); stress response syndrome (formerly known as adjustment disorder); dissociative disorder, formerly known as multiple personality disorder or "splitting personality," and depersonalization disorder; affectation disorder; sexual and gender disorders, such as sexual dysfunction, gender identity disorder, and sexual perversion; somatic symptom disorder, formerly known as psychosomatic disorder or somatic symptom disorder.

[0288] In some embodiments, mental illness 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, balance hallucinations, nociceptive hallucinations, thermal hallucinations, and time hallucinations, and combinations thereof.

[0289] In another aspect, this disclosure provides a method for treating central nervous system (CNS) diseases, conditions or symptoms and / or neurological diseases, conditions or symptoms, said method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein.

[0290] In another aspect, this disclosure provides a method for preventing central nervous system (CNS) diseases, conditions or symptoms and / or neurological diseases, conditions or symptoms, the method comprising administering to a subject in need a compound or pharmaceutical composition of formula (I) as described herein.

[0291] In some embodiments, the CNS disease, condition, or symptom and / or the neurological disease, condition, or symptom is selected from neurological diseases including neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease; early-onset dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, Parkinson's disease, and Parkinson's-related conditions, such as Parkinson's dementia, corticobasal degeneration, and supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial diseases; Fragile X syndrome; Angelman's syndrome. Syndrome; hereditary ataxia; neurogenic ear and eye movement disorders; neurodegenerative diseases of retinal myofascitis and lateral sclerosis; tardive dyskinesia; ADHD; attention deficit hyperactivity disorder and attention deficit disorder; restless legs syndrome; Tourette syndrome; schizophrenia; autism spectrum disorders; tuberous sclerosis; Tourette syndrome; cerebral palsy; reward system disorders, including eating disorders such as anorexia nervosa and bulimia nervosa; bulimia, trichotillomania, scratching, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology; and combinations thereof.

[0292] In another aspect, this disclosure provides a method for increasing neuronal plasticity, the method comprising contacting a neuronal cell with an amount sufficient to increase the neuronal plasticity of the neuronal cell as described herein with a compound or pharmaceutical composition of formula (I). "Neuronal plasticity" refers to the brain's ability to continuously change its structure and / or function throughout a subject's life. Examples of brain changes include, but are not limited to, the ability to adapt to or respond to internal and / or external stimuli (such as stimuli due to injury), and the ability to generate new neurites, dendritic spines, and synapses. Increasing neuronal plasticity includes, but is not limited to, promoting neuronal growth, promoting neurite formation, promoting synaptic formation, promoting dendrite formation, increasing dendritic branching complexity, increasing dendritic spine density, and increasing excitatory synapses in the brain. In some embodiments, increasing neuronal plasticity includes promoting neuronal growth, promoting neurite formation, promoting synaptic formation, promoting dendritic formation, increasing dendritic branching complexity, and increasing dendritic spine density.

[0293] In some embodiments, increasing neuronal plasticity can treat neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, mental disorders, depression, addiction, anxiety, post-traumatic stress disorder, treatment of antidepressant, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, traumatic brain injury, or substance use disorder.

[0294] In another aspect, this disclosure provides a method for treating weight, the method comprising administering an effective amount of the compound of the invention to a subject in need. Treating weight may include treating weight gain; weight loss; metabolic disorders; weight gain associated with drug intervention; weight gain associated with mental illness (including the mental illnesses described herein); eating disorders such as anorexia, bulimia, cachexia, etc.; eating behaviors; obesity; diabetes; insulin resistance; prediabetes; glucose intolerance; hyperlipidemia; and cardiovascular disease.

[0295] In another aspect, this disclosure provides a method for increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound or pharmaceutical composition of formula (I) as described herein in an amount sufficient to increase the dendritic spine density of the neuronal cell.

[0296] In some embodiments, Sholl analysis showed that the maximum number of dendritic crossings generated by the compound of formula (I) was increased by more than 1.0 times.

[0297] In another aspect, this disclosure provides a method for activating a serotonin receptor in cells of a biological sample or a patient, the method comprising administering to the cells a compound of formula (I) as defined in any of the embodiments disclosed herein. The serotonin receptor may be a 5-HT receptor subtype, preferably 5-HT. 2A and 5-HT2C One or two of them.

[0298] In some embodiments, the effective amount varies based on factors such as the disease state, age, sex, and / or weight of the subject or species. In some embodiments, the amount of one or more given compounds corresponding to the effective amount may vary based on factors such as the given drug or compound, drug formulation, route of administration, symptoms, type of disease or condition, and the identity of the subject being treated, but may be conventionally determined by those skilled in the art.

[0299] In some embodiments, the compound of formula (I) of this disclosure is administered once, twice, three times, or four times per year. In some embodiments, the compound of this disclosure is administered at least once per week. However, in another embodiment, the compound is administered to the subject approximately once every two weeks, three weeks, or one month. In another embodiment, the compound is administered approximately once per week to approximately once daily. In another embodiment, the compound is administered once, twice, three times, four times, five times, or six times daily. The length of the treatment period depends on a variety of factors, such as the severity of the disease, condition, or symptom, the age of the subject, the concentration and / or activity of the compound used, and / or combinations thereof. It should also be understood that the effective dose of the compound used for treatment may be increased or decreased during the course of a particular treatment regimen. Changes in dose can be produced and become apparent using 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 for a duration sufficient to treat the subject.

[0300] In some embodiments, the compounds of this application are administered to the subject at doses that of hallucinogens or psychotropic drugs, in combination with psychotherapy or therapy, and may be administered once, twice, three times, or four times per year. However, in some embodiments, the compounds are administered to the subject to the subject at doses that are not hallucinogens or psychotropic drugs, once daily, once every two days, once every three days, once weekly, once every two weeks, once monthly, once every two months, or once every three months.

[0301] The compounds of formula (I) of this disclosure can be used alone or in combination with other known agents that can be used to treat diseases, conditions, or symptoms by activating serotonin receptors (such as the compounds of this disclosure). One embodiment of this application, when used in combination with other known agents that can be used to treat diseases, conditions, or symptoms by activating serotonin receptors, is that the compound of formula (I) is administered simultaneously with these agents. As used herein, “simultaneous administration” of two substances to a subject means providing each of the two substances such that they are simultaneously active in the individual. The exact details of administration will depend on the pharmacokinetics of the two substances in the presence of each other and may include administering the two substances within hours of each other, or even administering the other substance within 24 hours of administering one substance (if pharmacokinetics are suitable). The design of suitable dosing regimens is conventional to those skilled in the art. In certain embodiments, the two substances will be administered substantially simultaneously, i.e., within minutes of each other, or in the form of a single composition containing both substances. Another embodiment of this application is the administration of a combination of agents to a subject in a non-simultaneous manner. In some embodiments, the compound of formula (I) of this disclosure is administered simultaneously or sequentially with another therapeutic agent in a single unit dosage form, or together in a single unit dosage form. Therefore, this application provides a single unit dosage form comprising one or more compounds of formula (I) as described herein, an additional therapeutic agent, and a pharmaceutically acceptable carrier.

[0302] In some embodiments, the compounds of this application are used or administered in an effective amount, which includes administering a dose or dosing regimen that does not have clinically significant hallucinogenic / psychopathic effects. In some embodiments, the compounds of this application are used or administered in an effective amount, which includes administering a dose or dosing regimen that provides human plasma dephosphatemized psilocybin Cmax of 4 ng / mL or less and / or human 5-HT. 2A A dose or dosing regimen in which the human CNS receptor occupancy is 40% or less, or which exhibits a human plasma dephosphatemized psilocybin Cmax of 1 ng / mL or less and / or human 5-HT 2A A dose or dosing regimen in which the human CNS receptor occupancy is 30% or less has a clinical effect similar to that of a dose or dosing regimen similar to that of a dose or dosing regimen in which human plasma dephosphated psilocybin Tmax is expressed for more than 60 minutes, more than 120 minutes, or more than 180 minutes. In some embodiments, the compounds of this application are used or administered in an effective amount, which includes administering a dose or dosing regimen in which a clinical effect similar to that of a dose or dosing regimen in which human plasma dephosphated psilocybin Tmax is expressed for more than 60 minutes, more than 120 minutes, or more than 180 minutes.

[0303] Reagent test kit In another embodiment, a kit or article is provided comprising one or more compounds, pharmaceutically acceptable salts, stereoisomers, solvates, metabolites or polymorphs and / or pharmaceutical compositions as described above.

[0304] In other embodiments, a kit is provided for the therapeutic applications mentioned above, the kit comprising: A container that contains one or more compounds, pharmaceutically acceptable salts, stereoisomers, solvates, metabolites or polymorphs and / or pharmaceutical compositions as described herein; A label or packaging insert that has instructions for use.

[0305] It should be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more features mentioned or apparent in the text or drawings. All these different combinations constitute various alternative aspects of the invention.

[0306] Example Scheme 1: Compounds of general formula (I) can be synthesized from appropriately substituted azido-indoles according to the sequence of steps outlined in Scheme 1 or a similar sequence of steps that a person skilled in the art might conceive of. The similar synthetic transformation sequence outlined in Scheme 1 has proven to be a feasible method for obtaining compounds of general formula (I). Friedel-Crafts acylation of the azido-indo starting material 7 provides a route to obtain intermediate 8, which can be subjected to chemiselective silane reduction conditions to provide an alkyl chloride intermediate 9. Nucleophilic substitution of the alkyl chloride with a substituted amine provides compounds of general formula (I) (exemplified by P-3). Those skilled in the art will recognize that the use of differentially substituted amines will allow for the acquisition of compounds of general formula (I) as disclosed herein. 2-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-3): Step 1 2-Chloro-1-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (8) At 0°C under N2, 5-methoxy-1 H -pyrrolo[2,3- bAlCl3 (10.8 g, 81.0 mmol) was added to a solution of pyridine (2.40 g, 16.2 mmol) in CH2Cl2 (48 mL), followed by the addition of chloroacetyl chloride (9.15 g, 81.0 mmol) in CH2Cl2 (7 mL). The reaction mixture was stirred at 0 °C for 1 hour and quenched by the addition of H2O (50 mL). The pH was adjusted to 10 with a saturated aqueous solution of Na2CO3. The mixture was filtered through celite diatomaceous earth, and the filter cake was washed with EtOAc (50 mL × 2). The filtrate was separated, and 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 EtOAc / THF (1:1, 200 mL) for 12 hours. The mixture was filtered, and the filtrate was concentrated and combined with the previous organic layer to produce 2-chloro-1-(5-methoxy-1-) as a grayish-white solid. H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-one (2.80 g, 77%). 1 H NMR (400 MHz, DMSO- d 6 ): δ 12.58 (br, 1H), 8.53 (s, 1H), 8.10 (d, J = 2.8 Hz, 1H), 7.96 (d, J = 2.8 Hz, 1H), 4.90 (s, 2H), 3.86 (s, 3H). LCMS (ESI+): m / z 225.1, 227.1 [M+H] + HPLC purity (220 nm): 100%.

[0307] Step 2: 3-(2-Chloroethyl)-5-methoxy-1 H -pyrrolo[2,3- b ]Pyridine (9) To 2-chloro-1-(5-methoxy-1 H -pyrrolo[2,3- bPyridin-3-yl)ethyl-1-one 8 (1.40 g, 6.23 mmol) was added to a solution of TFA (10 mL) with Et3SiH (5.07 g, 43.6 mmol). The reaction mixture was stirred at 25 °C for 12 h. The reaction mixture was adjusted to pH 9 with a saturated aqueous solution of Na2CO3 and extracted with EtOAc (80 mL × 2). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under vacuum to produce crude 3-(2-chloroethyl)-5-methoxy-1-one as a grayish-white solid. H -pyrrolo[2,3- b Pyridine 9 (1.40 g). 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.29 (br, 1H), 7.94 (d, J = 2.8 Hz, 1H), 7.60 (d, J = 2.4 Hz, 1H), 7.32 (d, J = 2.4 Hz, 1H), 3.82 - 3.87 (m, 5H), 3.12 (t, J = 7.4 Hz, 2H). LCMS (ESI+): m / z 211.1, 213.1 [M+H] + HPLC purity (220 nm): 98.5% Step 3: 2-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-3) To crude 3-(2-chloroethyl)-5-methoxy-1 H -pyrrolo[2,3- bNaI (996 mg, 6.65 mmol) was added to a mixture of pyridine (1.40 g) in Me2NH (2.0 M in THF, 28 mL) 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 (NH3 aqueous solution + NH4HCO3)-ACN]; B: 1-30%, 10 min) to give 2-(5-methoxy-1-methyl)-2-(NH3-2-methyl)-2-(NH4-2-(NH3-2-(NH4 ... H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine P-3 (397 mg, 29%, via 2 steps). 1 H NMR (400 MHz, MeOD- d 4 ): δ 7.91 (d, J = 2.8 Hz, 1H), 7.56 (d, J = 2.8 Hz, 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 / z 220.2 [M+H] + HPLC purity (220 nm): 100%.

[0308] Step 3a: 2-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine hydrochloride (P-3·HCl) Dropwise over 10 minutes to 2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N1-Dimethylethyl-1-amine (100 mg, 0.45 mmol) was added to an ice-cold (0°C) solution of anhydrous Et₂O (5 mL) and absolute EtOH (1 mL) containing 2 M HCl until the pH of the reaction solution became acidic. The resulting precipitate was collected by filtration and dried overnight in a vacuum desiccator to produce 2-(5-methoxy-1-)-dimethylethyl-1-amine as hydrochloride. H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (78 mg, 68%), the product is a white solid. 1 H NMR (400MHz, MeOD- d 4 ): δ 7.91 (d, J = 2.8 Hz, 1H), 7.56 (d, J = 2.8 Hz, 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 (220 nm): 99.7%.

[0309] Option 2: In some cases, alternative synthesis of compounds of general formula (I) is used as outlined in Option 2. Nucleophilic substitution of the chlorine of intermediate 8 with a suitably substituted amine yields an aminoacetyl-1-one. A subsequent two-step reduction allows for the yield of compounds of general formula (I) (illustrated by P-17). Those skilled in the art will recognize that the use of differentially substituted amines will allow for the yield of compounds of general formula (I) as disclosed herein. 2-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Diethylethyl-1-amine (P-17): Step 1 2-(diethylamino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (40) 2-chloro-1-(5-methoxy-1 H -pyrrolo[2,3- bA solution of pyridin-3-yl)ethyl-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. The reaction solution was then diluted with water (30 mL) and extracted with EtOAc (10 mL × 2). The combined organic matter was washed with brine (40 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to produce a crude 2-(diethylamino)-1-(5-methoxy-1-yl)-one as a yellow solid. H -pyrrolo[2,3- b 281 mg of pyridin-3-yl)ethyl-1-one was used in subsequent steps without purification. LCMS (ESI+): m / z 262.2 [M+H] + .

[0310] Step 2 2-(diethylamino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl) ethanol-1-ol (41) At ambient temperature, crude 2-(diethylamino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b 189 mg of pyridin-3-yl)ethyl-1-one was added to a solution of MeOH (5 mL) and H₂O (1.6 mL) with NaBH₄ (3.00 g, 79.3 mmol), and the mixture was stirred overnight. The reaction solution 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 (15 mL), dried over Na₂SO₄, and concentrated under vacuum to produce a crude 2-(diethylamino)-1-(5-methoxy-1-yl)-one as a grayish-white solid. H -pyrrolo[2,3- b 170 mg of pyridin-3-yl)ethanol-1-ol was used without further purification. LCMS (ESI+): m / z 264.2 [M+H] + .

[0311] Step 3 2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Diethylethyl-1-amine (P-17) At ambient temperature, crude 2-(diethylamino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-one (170 mg) and Et3SiH (0.20 mL, 1.25 mmol) were added to a stirred solution of BF3·Et2O (0.10 mL, 0.80 mmol) in MeCN (4 mL), and the mixture was stirred overnight. The reaction solution was quenched with water (5 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (15 mL), 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-1-one) as a grayish-white solid. H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Diethylethyl-1-amine (60 mg, 22%, via 3 steps). 1 H NMR (300 MHz, MeOD- d 4 ): δ 7.95 (d, J =2.7 Hz, 1 H), 7.62 (d, J = 2.2 Hz, 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 = 7.3 Hz, 6H). LCMS (ESI+): R T = 3.33min, m / z 248.3 [M+H] + HPLC purity (220 nm): 98.6%.

[0312] 2-(5-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dipropylethyl-1-amine (P-18): Step 1 2-(dipropylamino)-1-(5-methoxy-1 H -pyrrolo[2,3- b]pyridin-3-yl)ethyl-1-one (42) 2-Chloro-1-(5-methoxy-1) H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-1-one (250 mg, 1.11 mmol), NaI (250 mg, 1.67 mmol), and dipropylamine (1.13 g, 11.1 mmol) was added to DMAc (7 mL), and the mixture was stirred at room temperature for 2 hours. The reaction solution was quenched with water (30 mL) and extracted with EtOAc (10 mL × 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to produce crude 2-(diethylamino)-1-(5-methoxy-1-ethylamino)-1-one as a yellow solid. H -pyrrolo[2,3- b 350 mg of pyridin-3-yl)ethyl-1-one was used in subsequent steps without purification. LCMS (ESI+): m / z 290.4 [M+H] + .

[0313] Step 2 2-(dipropylamino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)Ethyl-1-ol (43) At ambient temperature, crude 2-(dipropylamino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-1-one (350 mg) in MeOH (5 mL) was mixed with NaBH4 (3.00 g, 79.3 mmol) and stirred overnight. The reaction mixture 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 Na2SO4, and concentrated under vacuum to produce crude 2-(dipropylamino)-1-(5-methoxy-1-yl)-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl)ethyl-1-yl) ... H -pyrrolo[2,3- b 280 mg of pyridin-3-yl)ethanol-1-ol was used without further purification. LCMS (ESI+): m / z 292.3 [M+H] + .

[0314] Step 3 2-(5-methoxy-1 H -pyrrolo[2,3- b]pyridin-3-yl)- N , N -Dipropylethyl-1-amine (P-18) At ambient temperature, crude 2-(dipropylamino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-ol (280 mg) and Et3SiH (0.40 mL, 2.50 mmol) were added to a stirred solution of BF3·Et2O (0.30 mL, 2.43 mmol) in MeCN (6 mL), and the mixture was stirred overnight at room temperature. The reaction solution was quenched with H2O (5 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (15 mL), 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-1-yl)-2-ethyl-1-ol as a grayish-white solid. H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dipropylethyl-1-amine (80 mg, 26%, via 3 steps). 1 H NMR (300 MHz, MeOD- d 4 ): δ 7.95 (d, J = 2.6 Hz, 1H), 7.64 (d, J = 2.6 Hz, 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 = 7.3 Hz, 4H), 1.00(t, J = 7.3 Hz, 6H). LCMS (ESI+): m / z 276.3 [M+H] + HPLC purity (220 nm): 97.8%.

[0315] Scheme 3: In some cases, obtaining compounds of general formula (I) via Scheme 3 requires the introduction of a suitable protecting group into the reactive pyrroloamine. Base-mediated SEM protection of common intermediate 8 yields a protected azido-indole 44. This intermediate demonstrates suitability for the previously described synthetic route (Scheme 5) involving nucleophilic substitution of the chlorine of intermediate 44 by a suitably substituted amine. Subsequent two-step reduction simultaneously removes the SEM protecting group, thus providing a route for obtaining compounds of general formula (I) (illustrated by P-19). Those skilled in the art will recognize that utilizing differentially substituted amines will allow for the acquisition of alternative derivatives of general formula (I) as disclosed herein. N -Isopropyl- N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)prop-2-amine (P-19): Step 1 2-Chloro-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (44) At 0 °C, 2-(chloromethoxy)ethyl)trimethylsilane (2.50 mL, 14.1 mmol) was used to treat 2-chloro-1-(5-methoxy-1-ethyl)-trimethylsilane. H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-1-one (1 g, 4.45 mmol) and DIPEA (3.00 mL, 22.0 mmol) in DMAc (10 mL) was treated and then stirred at ambient temperature for 5 hours. The reaction mixture was then quenched with H2O (30 mL) and extracted with EtOAc (10 mL × 2). The combined organic layers were washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was subjected to column chromatography (petroleum ether: EtOAc - 7:1) to produce crude 2-chloro-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b 420 mg of pyridin-3-yl)ethyl-1-one was used in subsequent steps without further purification. LCMS (ESI+): m / z 355.3, 357.2 [M+H] + .

[0316] Step 2 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl) ethyl-1-one (45) The crude 2-chloro-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-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 extracted with EtOAc (10 mL × 2). The combined organic matter was washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography (petroleum ether / EtOAc, v / v, 3 / 1) to yield crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1- H -pyrrolo[2,3- b Pyridin-3-yl)aceto-1-one (146 mg). LCMS (ESI+): m / z 420.5 [M+H] + .

[0317] Step 3 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)Ethyl-1-ol (46) At ambient temperature, crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b145 mg of pyridin-3-yl)ethyl-1-one was added to a solution of MeOH (2 mL) and H₂O (0.4 mL) with NaBH₄ (3.00 g, 79.3 mmol), and the product was stirred overnight. The reaction mixture 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 Na₂SO₄, and concentrated under vacuum to produce crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1- H -pyrrolo[2,3- b 110 mg of pyridin-3-yl)ethyl-1-ol was used in subsequent steps without further purification. LCMS (ESI+): m / z 422.4 [M+H] + .

[0318] Step 4 : N -Isopropyl- N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)prop-2-amine (P-19) At ambient temperature, crude 2-(diisopropylamino)-1-(5-methoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethanol-1-ol (110 mg) and Et3SiH (300 mg, 2.58 mmol) were added to a stirred solution of BF3·Et2O (0.20 mL, 1.62 mmol) in MeCN (2 mL), and the mixture was stirred overnight. The reaction solution was quenched with H2O (5 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (15 mL), 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 a grayish-white solid. N -Isopropyl- N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)prop-2-amine (20 mg, 2%, via 4 steps). 1 H-NMR (300 MHz, MeOD- d4 ): δ 7.96 (d, J = 2.5 Hz, 1H), 7.55 (d, J = 2.4 Hz,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 = 6.6 Hz, 12H). LCMS (ESI+): m / z 276.4 [M+H] + HPLC purity (220 nm): 97.4%.

[0319] N -Ethyl-2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N -Methylethyl-1-amine (P-20): Step 1 2-(ethyl(methyl)amino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl) ethyl-1-one (47) 2-chloro-1-(5-methoxy-1 H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-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 solution was diluted with water (30 mL) and then extracted with EtOAc (10 mL × 2). The combined organic matter was washed with brine (40 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to produce crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1-ethyl)amino(methyl ... H -pyrrolo[2,3- b 216 mg of pyridin-3-yl)ethyl-1-one was used in subsequent steps without purification. LCMS (ESI+): m / z 248.3 [M+H] + .

[0320] Step 2 2-(ethyl(methyl)amino)-1-(5-methoxy-1H -pyrrolo[2,3- b ]Pyridin-3-yl)Ethyl-1-ol (48) At ambient temperature, the crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b 205 mg of pyridin-3-yl)ethyl-1-one was added to a solution of MeOH / H2O (6 / 2 v / v, 8 mL) with NaBH4 (3.00 g, 79.3 mmol), and the mixture was stirred overnight. The reaction solution 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 over anhydrous Na2SO4, and concentrated under vacuum to produce crude 2-(dipropylamino)-1-(5-methoxy-1-yl)-one as a white solid. H -pyrrolo[2,3- b 185 mg of pyridin-3-yl)ethanol was used in the next step without further purification. LCMS (ESI+): m / z 250.2 [M+H] + .

[0321] Step 3 : N -Ethyl-2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N 1-Methylethyl-1-amine (P-20·HCl) At ambient temperature, the crude 2-(ethyl(methyl)amino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b Pyridin-3-yl)ethanol-1-ol (185 mg) and Et3SiH (0.40 mL, 2.5 mmol) were added to a stirred solution of BF3·Et2O (0.50 mL, 4.05 mmol) in MeCN (4 mL), and the mixture was stirred overnight. The reaction solution was quenched with saturated Na2CO3 aqueous solution (5 mL) and extracted with CH2Cl2:MeOH (10:1 v / v, 5 mL × 2). The combined organic layers were washed with brine (15 mL), 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 provide a grayish-white solid. N -Ethyl-2-(5-methoxy-1 H-pyrrolo[2,3- b ]pyridin-3-yl)- N 1-Methylethyl-1-amine hydrochloride (30 mg, 12%, via 3 steps). 1 H NMR (300 MHz, MeOD- d 4 ): δ 8.56 (d, J = 2.1 Hz, 1H), 8.25 (d, J = 2.0 Hz, 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 = 7.3 Hz, 3H). . LCMS (ESI+): m / z234.2 [M+H] + HPLC purity (220 nm): 98.6%.

[0322] N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N -Methylpropyl-2-amine (P-21): Step 1 2-(isopropyl(methyl)amino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (49) 2-chloro-1-(5-methoxy-1 H -pyrrolo[2,3- b A solution of pyridin-3-yl)ethyl-1-one (300 mg, 1.33 mmol), NaI (300 mg, 2.00 mmol), and methyl(propyl-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 EtOAc (10 mL × 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to produce a crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1-yl)amino solid in yellow form. H -pyrrolo[2,3- b275 mg of pyridin-3-yl)ethyl-1-one was used as the crude product in subsequent steps without purification. LCMS (ESI+): m / z 262.2 [M+H] + .

[0323] Step 2 2-(isopropyl(methyl)amino)-1-(5-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)Ethyl-1-ol (50) At ambient temperature, the crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1-) H -pyrrolo[2,3- b 275 mg (1.05 mmol) of pyridin-3-yl)ethyl-1-one was added to a solution of MeOH / H2O (8 mL, v / v, 6 / 2) with NaBH4 (3.00 g, 79.3 mmol). The resulting mixture was stirred overnight at ambient temperature. The reaction mixture 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 Na2SO4, and concentrated under vacuum to produce a crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1-yl)-one as a white solid. H -pyrrolo[2,3- b 207 mg of pyridin-3-yl)ethanol-1-ol was used in the next step without further purification. LCMS (ESI+): m / z 264.3 [M+H] + .

[0324] Step 3 : N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N -Methylpropyl-2-amine (P-21) At ambient temperature, the crude 2-(isopropyl(methyl)amino)-1-(5-methoxy-1-) H -pyrrolo[2,3- bPyridin-3-yl)ethanol-1-ol (207 mg) and Et3SiH (0.40 mL, 2.50 mmol) were added to a stirred solution of BF3·Et2O (0.30 mL, 2.43 mmol) in MeCN (4 mL), and the mixture was stirred overnight. The reaction solution was quenched with saturated Na2CO3 aqueous solution (5 mL) and then extracted with CH2Cl2:MeOH (10:1 v / v, 2 x 5 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under vacuum. The resulting residue was purified by preparative thin-layer chromatography (CH2Cl2 / MeOH, v / v, 8 / 1) to obtain a grayish-white solid. N -(2-(5-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N 2-Methylpropyl-2-amine (32 mg, 10%, via 3 steps). 1 H NMR (300 MHz, MeOD- d 4 ): δ 7.95 (d, J = 2.4 Hz, 1H), 7.65 (d, J = 2.5 Hz, 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 = 6.0 Hz, 6H). LCMS (ESI+): m / z 248.3 [M+H] + HPLC purity (220nm): 96%.

[0325] N , N -dimethyl-2-(5-methyl-1- H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-22): Step 1 2-Chloro-1-(5-methyl-1-) H -pyrrolo[2,3- b ]pyridin-3-yl) ethyl-1-one (52) 5-methyl-1 H -pyrrolo[2,3-b The mixture of pyridine (500 mg, 3.78 mmol) in CH2Cl2 (15 mL) was degassed and purged three times with N2, followed by the addition of AlCl3 (2.52 g, 18.9 mmol) under N2 at 0 °C. After stirring at 0 °C for 5 min, 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 h. The reaction solution was quenched with water (15 mL) at 0 °C and adjusted to pH 9 with aqueous Na2CO3 solution, filtered, and the filter cake was washed with EtOAc (30 mL × 4). The aqueous phase was separated and extracted with EtOAc (20 mL × 3). The combined organic matter was washed with brine (10 mL × 2), dried over anhydrous Na2SO4, and concentrated under reduced pressure to provide crude 2-chloro-1-(5-methyl-1-chloroacetyl) as a yellow solid. H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-one (650 mg), the crude product was used in the next step without purification.

[0326] Step 2: 3-(2-Chloroethyl)-5-methyl-1 H -pyrrolo[2,3- b Pyridine (53) To 2-chloro-1-(5-methyl-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-one (650 mg) was added to a solution of TFA (10 mL) with Et3SiH (5.10 g, 43.9 mmol), 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 and extracted with EtOAc (10 mL × 3). The combined organic matter was washed with brine (10 mL × 2), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether / EtOAc, v / v, 10:1 to 1:1) to produce 3-(2-chloroethyl)-5-methyl-1-ethyl-1-one as a grayish-white solid. H -pyrrolo[2,3- b Pyridine (350 mg). LCMS (ESI+): m / z 195.1 [M+H] + .

[0327] Step 3: 2-(5-methyl-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N ,N -Dimethylethyl-1-amine (P-22) To 3-(2-chloroethyl)-5-methyl-1 H -pyrrolo[2,3- b A solution of pyridine (200 mg) in THF (3 mL) was mixed with NaI (462 mg, 3.08 mmol) and THF containing 2 M Me₂NH (1.03 mL, 2.06 mmol), and the solution was stirred in a sealed tube at 90 °C for 12 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm; mobile phase: [water (NH₃)-ACN]; B: 12-42%, 9 min) to provide 2-(5-methyl-1-methyl-1-methyl-2 ... H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (25 mg, 6%, via 3 steps). 1 H NMR (400 MHz, CDCl3): δ 9.11(br s, 1H), 8.13 (d, J = 2.0 Hz, 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 / z 204.0[M+H] + HPLC purity (220 nm): 96.5% N -Ethyl- N -Methyl-2-(5-methyl-1-methyl) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (P-23): Step 1 : N -Ethyl- N -Methyl-2-(5-methyl-1-methyl) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-23) To 3-(2-chloroethyl)-5-methyl-1 H -pyrrolo[2,3- b The product was stirred at 50 °C for 12 h with K₂CO₃ (213 mg, 1.54 mmol) and ethyl(methyl)amine (182 mg, 3.08 mmol) added to a solution of pyridine (200 mg, 1.03 mmol) in DMF (3 mL). The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH₄HCO₃)-ACN]; B: 12-42%, 9 min) to provide a grayish-yellow oil. N -Ethyl- N -Methyl-2-(5-methyl-1-methyl) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (25 mg, 5%, via 3 steps). 1 H NMR (400 MHz, CDCl3): δ 9.08 (br s, 1H), 8.14 (d, J = 1.6 Hz, 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 = 7.2 Hz, 2H), 2.45(s, 3H), 2.38 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H). LCMS (ESI+): m / z 218.0 [M+H] + HPLC purity (220 nm): 98.2%.

[0328] N , N -Dimethyl-2-(5-fluoro-1- H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (P-24): Step 1 2-Chloro-1-(5-Fluoro-1) H -pyrrolo[2,3- b]pyridin-3-yl) ethyl-1-one (55) 5-Fluoro-1 H -pyrrolo[2,3- b The mixture of pyridine (1.00 g, 7.35 mmol) in CH2Cl2 (7 mL) was degassed and purged three times with N2, followed by the addition of AlCl3 (4.90 g, 36.8 mmol) under N2 at 0 °C. After stirring at 0 °C for 5 min, 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 h. The reaction mixture was quenched with water (20 mL) at 0 °C and the pH was adjusted to 9 with an aqueous Na2CO3 solution, and then filtered. The filter cake was washed with EtOAc (30 mL × 4), and the aqueous phase was separated, diluted with H2O (30 mL), and further extracted with EtOAc (20 mL × 3). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to provide crude 2-chloro-1-(5-fluoro-1-) as a yellow solid. H -pyrrolo[2,3- b 1.16 g of pyridin-3-yl)ethyl-1-one was used in the next step without purification.

[0329] Step 2: 3-(2-Chloroethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (56) To 2-chloro-1-(5-fluoro-1) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-one (1.16 g, 5.46 mmol) was added to a solution of TFA (10 mL) with Et3SiH (3.64 g, 31.3 mmol), 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 extracted with EtOAc (75 mL × 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 wet-milled at ambient temperature with MTBE:petroleum ether (1:5 v / v, 20 mL) for 30 minutes and filtered to produce 3-(2-chloroethyl)-5-fluoro-1-one as a yellow solid. H -pyrrolo[2,3- b Pyridine (389 mg). LCMS (ESI+): m / z 199.0 [M+H] + .

[0330] Step 3: 2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-24) To 3-(2-chloroethyl)-5-fluoro-1 H -pyrrolo[2,3- b A solution of pyridine (50.0 mg, 0.25 mmol) in THF (5 mL) was mixed with NaI (56.6 mg, 0.39 mmol) and THF containing 2 M Me₂NH (0.5 mL, 1.01 mmol), and the solution 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 EtOAc (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 purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH₃)-ACN]; B: 18-48%, 10 min) to provide 2-(5-fluoro-1-hydroxymethyl)-2-(NH₃-1-ethylhexyl) as a yellow solid. H -pyrrolo[2,3- b ]pyridin-3-yl)- N,N -Dimethylethyl-1-amine (10.3 mg, 5%, via 3 steps). 1 H NMR (400 MHz, CDCl3): δ 9.11 (br, 1H), 8.17 (t, J = 2.2 Hz, 1H), 7.60 (dd, J =8.9, 2.7 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 2.89 (t, J = 7.6 Hz, 2H), 2.62(t, J = 6.9 Hz, 2H), 2.35 (s, 6H). 19 F NMR (400 MHz, CDCl3): δ -139.4. LCMS (ESI+): m / z 208.2 [M+H] + HPLC purity (220 nm): 98.0%.

[0331] N -Ethyl-N -Methyl-2-(5-fluoro-1- H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (P-25): Step 1 : N -Ethyl- N -Methyl-2-(5-fluoro-1- H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (P-25) To 3-(2-chloroethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (200 mg, 1.01 mmol) was added to a solution of DMF (5 mL) with K2CO3 (306 mg, 2.21 mmol) and ethyl(methyl)amine (238 mg, 4.03 mmol), and the solution 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 EtOAc (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 purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm; mobile phase: [water (NH3 aqueous solution)-ACN]; B: 18-48%, 10 min) to provide a yellow solid. N -Ethyl- N -Methyl-2-(5-fluoro-1- H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-amine (57.0 mg, 7%, via 3 steps). 1 H NMR (400 MHz, CDCl3): δ 9.19 (br s, 1H), 8.16 (t, J = 2.2 Hz, 1H), 7.61 (dd, J =8.9, 2.6 Hz, 1H), 7.20 (d, J = 2.1 Hz, 1H), 2.87-2.91 (m, 2H), 2.66-2.70 (m,2H), 2.53 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H). 19F NMR (400 MHz, CDCl3): δ -139.4. LCMS (ESI+): m / z 222.2 [M+H] + HPLC purity (220 nm): 98.0%.

[0332] Scheme 4: Compounds of general formula (I) can be synthesized from appropriately substituted azido-indoles according to the sequence of steps outlined in Scheme 4 or a sequence of steps similar to that conceivable to a person skilled in the art. Friedel-Crafts acylation of the azido-indole starting material 10 provides a route to obtain intermediate 11, which can be subjected to chemoselective silane reduction conditions to provide alkyl chloride intermediate 12. Nucleophilic substitution of the alkyl chloride with a substituted amine provides compounds of general formula (I) (exemplified by P-4). 2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-4): Step 1 2-Chloro-1-(4-methoxy-1) H -pyrrolo[2,3- b ]pyridin-3-yl) ethyl-1-one (11) To 4-methoxy-1 H -pyrrolo[2,3- b AlCl3 (9.90 g, 74.2 mmol) and chloroacetyl chloride (8.39 g, 74.2 mmol) were added to a solution of pyridine (2.20 g, 14.8 mmol) in CH2Cl2 (14 mL). The mixture was stirred at 0 °C for 1.5 h. The reaction mixture was quenched by adding H2O (20 mL) at 0 °C and then adjusted to pH 9 with a saturated aqueous solution of Na2CO3. The mixture was filtered and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and allowed to stand. The filter cake was wet-milled at 20 °C with THF / EtOAc (1:1, 100 mL) for 2 h. The filtrate was combined with the organic layers and concentrated under vacuum to yield the title compound (3.10 g, 93%) as a pale yellow solid. 1 H NMR: (400 MHz, DMSO- d 6): δ 12.5 (br s, 1H), 8.27 (s, 1H), 8.21 (d, J = 5.6 Hz, 1H), 6.84 (d, J = 5.6 Hz, 1H), 4.97 (s, 2H), 3.95 (s, 3H). LCMS (ESI+): m / z 225.1 [M+H] + .

[0333] Step 2: 3-(2-Chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- b Pyridine (12) To 2-chloro-1-(4-methoxy-1 H -pyrrolo[2,3- b Et3SiH (8.19 g, 70.4 mmol) was added to a solution of pyridin-3-yl)ethyl-1-one (2.26 g, 10.1 mmol) in TFA (13.2 mL). The mixture was stirred at 20 °C for 16 h. The reaction mixture was adjusted to pH = 9 with saturated aqueous Na2CO3 solution and then extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under vacuum to produce 3-(2-chloroethyl)-4-methoxy-1-one as a red solid. H -pyrrolo[2,3- b Pyridine (12) (2.00 g, 94%). 1 H NMR: (400 MHz, DMSO- d 6): δ 8.06 (d, J = 5.6 Hz, 1H), 7.14 (d, J = 1.6 Hz, 1H), 6.63 (d, J = 5.6 Hz, 1H), 5.20 (br s, 1H), 3.93 (s, 3H), 3.81 (t, J = 7.4 Hz, 2H), 3.16 (t, J = 7.4 Hz, 2H). LCMS (ESI+): m / z 211.1 [M+H] + .

[0334] Step 3: 2-(4-methoxy-1 H -pyrrolo[2,3- b]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-4) Sodium iodide (1.14 g, 7.6 mmol) was used to treat 3-(2-chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- b Pyridine (1.6 g, 7.6 mmol) was treated with a solution of THF (32.3 mL, 8.5 equivalents, 64.6 mmol) containing 2 M Me₂NH₃, and the solution was stirred under reflux for 24 hours. Upon completion, the reaction mixture was filtered, and the filter cake was eluted with THF (20 mL). The combined filtrates were concentrated under vacuum, and the residue was purified by preparative HPLC (column: Waters Xbridge preparative OBD C18 150 * 40 mm * 10 µm; mobile phase: [water (NH₄HCO₃)-ACN]; B: 1%–30%, 8 min) to yield 2-(4-methoxy-1-methyl)pyridine as a pale yellow solid (600 mg, 36%). H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (0.6 g, 2.74 mmol). 1 H-NMR (400 MHz, MeOD- d 4 ): δ 8.03 (d, J = 5.6 Hz, 1H), 7.00 (s, 1H), 6.64 (d, J = 5.6 Hz, 1H), 4.00 (s, 3H), 2.96 -3.03 (m, 2H), 2.60 - 2.68 (m, 2H), 2.34 (s, 6H). LCMS (ESI+): m / z 220.2 [M+H] + HPLC purity (220 nm): 100%.

[0335] Step 3a: 2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine hydrochloride (P-4·HCl) Dropwise over 10 minutes to 2-(4-methoxy-1 H -pyrrolo[2,3-b ]pyridin-3-yl)- N , N 1-Dimethylethyl-1-amine (0.2 g, 0.91 mmol) was added to an ice-cold (0 °C) solution of anhydrous Et₂O (5 mL) and absolute EtOH (1 mL) containing 2 M HCl until the pH of the reaction solution became acidic. The resulting precipitate was collected by filtration and dried overnight in a vacuum desiccator to produce 2-(4-methoxy-1-)-dimethylethyl-1-amine as hydrochloride. H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (120 mg, 52%), the product is a white solid. 1 H NMR (400 MHz, DMSO-) d 6 ): δ 12.47 (s, 1H), 10.55 (br. s, 1H), 8.38 (d, J = 6.6 Hz, 1H), 7.40 (d, J = 2.2 Hz, 1H), 7.07 (d, J = 6.6 Hz, 1H), 4.15 (s, 3H), 3.30 -3.16 (m, 4H), 2.81 (d, J = 4.8 Hz, 6H). 13 C NMR (100 MHz, DMSO- d 6 ): 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%.

[0336] N , N -Diethyl-2-(4-methoxy-1 H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-amine (P-26) To 3-(2-chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- bA solution of pyridine (500 mg, 2.37 mmol) in THF (5 mL) was mixed with NaI (534 mg, 3.56 mmol) and Et₂NH (1.74 g, 23.8 mmol), and the mixture was stirred at 100 °C for 48 hours. The mixture was then filtered, and the filter cake was washed with THF (5 mL). The filtrate was concentrated under reduced pressure, and the residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH₄HCO₃)-ACN]; B: 5-35%, 9 min) to produce a pale yellow solid. N,N -Diethyl-2-(4-methoxy-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-26) (100 mg, 17%). 1 H NMR (400MHz, MeOD- d 4 ): δ 8.05 (d, J = 5.7 Hz, 1H), 7.02 (s, 1H), 6.66 (d, J = 5.7 Hz,1H), 4.02 (s, 3H), 2.97-3.02 (m, 2H), 2.81-2.85 (m, 2H), 2.74 (q, J = 7.2 Hz, 4H), 1.16 (t, J = 7.2 Hz, 6H). LCMS (ESI+): m / z 248.1 [M+H] + HPLC purity (220 nm): 96.9%.

[0337] N -Isopropyl- N -(2-(4-methoxy-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl)prop-2-amine (P-27) To 3-(2-chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- bA solution of pyridine (500 mg, 2.37 mmol) in THF (5 mL) was mixed with NaI (534 mg, 3.56 mmol) and diisopropylamine (2.40 g, 23.7 mmol), and the mixture was stirred at 100 °C for 48 hours. The mixture was then filtered, and the filter cake was washed with THF (5 mL). The filtrate was concentrated under reduced pressure, and the residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH4HCO3)-ACN]; B: 10-40%, 9 min) to produce a pale yellow solid. N -Isopropyl- N -(2-(4-methoxy-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl)prop-2-amine (P-27) (14.4 mg, 2%). 1 H NMR (400 MHz, MeOD- d 4 ): δ 8.04 (br d, J = 3.2 Hz, 1H), 7.00 (s, 1H), 6.65 (d, J =5.7 Hz, 1H), 4.00 (s, 3 H), 3.16 (hept, J = 6.5 Hz, 2H), 2.90-2.94 (m, 2H), 2.72-2.77 (m, 2H), 1.14 (d, J = 6.5 Hz, 12H). LCMS (ESI+): m / z 276.1 [M+H] + HPLC purity (220 nm): 97.1%.

[0338] N -Ethyl-2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N -Methylethyl-1-amine (P-28) To 3-(2-chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- bA solution of pyridine (200 mg, 0.95 mmol) in THF (2 mL) was mixed with NaI (213 mg, 1.42 mmol) and ethyl(methyl)amine (561 mg, 9.49 mmol), and the mixture was stirred at 100 °C for 48 hours. The mixture was then filtered, and the filter cake was washed with THF (2 mL). The filtrate was concentrated under reduced pressure, and the residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH4HCO3)-ACN]; B: 5-35%, 9 min) to produce a pale yellow solid. N -Ethyl-2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)- N -Methylethyl-1-amine (P-28) (64.0 mg, 29%). 1 H NMR (400 MHz, MeOD- d 4 ): δ 8.07 (d, J = 5.7 Hz, 1H), 7.08 (s, 1H), 6.68 (d, J =5.7 Hz, 1H), 4.03 (s, 3H), 3.06-3.14 (m, 2H), 2.96-3.03 (m, 2H), 2.87 (q, J =7.2 Hz, 2H), 2.60 (s, 3H), 1.23 (t, J = 7.2 Hz, 3H). LCMS (ESI+): m / z 233.15[M+H] + HPLC purity (220 nm): 96.9%.

[0339] N -(2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N 2-Methylpropyl-2-amine (P-29) To 3-(2-chloroethyl)-4-methoxy-1 H -pyrrolo[2,3- bA solution of pyridine (150 mg, 0.71 mmol) in THF (2 mL) was mixed with NaI (160 mg, 1.07 mmol) and methyl(propyl-2-yl)amine (521 mg, 7.12 mmol), 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 purified by preparative HPLC (column: Waters Xbridge preparative OBD C18 (150 * 40 mm * 10 µm); mobile phase: [water (NH4HCO3)-ACN]; B: 0-30%, 15 min) to produce a pale yellow solid. N -(2-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N -Methylpropyl-2-amine (P-29) (120 mg, 68%). 1 H NMR (400 MHz, MeOD- d 4 ): δ 8.04 (d, J = 5.7 Hz, 1H), 7.01 (s, 1 H), 6.65 (d, J = 5.7 Hz, 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 = 6.5 Hz, 6H). LCMS (ESI+): m / z 248.1 [M+H] + HPLC purity (220 nm): 96.2%.

[0340] N , N -dimethyl-2-(4-methyl-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-30): Step 1 2-Chloro-1-(4-methyl-1-) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (58) 4-methyl-1 H -pyrrolo[2,3- bThe mixture of pyridine (500 mg, 3.78 mmol) in CH2Cl2 (15 mL) was degassed and purged three times with N2, followed by the addition of AlCl3 (2.52 g, 18.9 mmol) at 0 °C under N2. After stirring at 0 °C for 5 min, 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 h. The reaction mixture was then cooled to 0 °C, quenched with water (20 mL), and then saturated Na2CO3 aqueous solution was added until the solution reached pH 9. The mixture was then filtered, and the filter cake was washed with EtOAc (30 mL × 4), and the aqueous phase was separated and extracted with EtOAc (20 mL × 3). The combined organic matter was washed with brine (15 mL × 2), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure to provide 2-chloro-1-(4-methyl-1-chloroacetyl) as a yellow solid. H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-one (58) (850 mg), the crude product was used for the next step without purification.

[0341] Step 2: 3-(2-Chloroethyl)-4-methyl-1 H -pyrrolo[2,3- b Pyridine (59) To 2-chloro-1-(4-methyl-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-one (800 mg) was added to a solution of TFA (10 mL) with Et3SiH (4.11 g, 35.3 mmol), 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 a saturated aqueous solution of Na2CO3 and extracted with EtOAc (10 mL × 3). The combined organic matter was washed with brine (10 mL × 2), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether: EtOAc 10:1 to 1:2) to produce 3-(2-chloroethyl)-4-methyl-1-ethyl-1-one as a white solid. H -pyrrolo[2,3- b Pyridine (59) (310 mg, 42%, via 2 steps). LCMS (ESI+): m / z 195.0.

[0342] Step 3: N , N -dimethyl-2-(4-methyl-1 H-pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-30) 3-(2-chloroethyl)-4-methyl-1 H -pyrrolo[2,3- b A mixture of pyridine (50.0 mg, 257 µmol), K₂CO₃ (53.3 mg, 0.39 mmol), and Me₂NH₃ (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 EtOAc (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH₃)-ACN]; B: 18-48%, 10 min) to provide a white solid. N,N -dimethyl-2-(4-methyl-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-30) (15.0 mg, 14%). 1 H NMR (400 MHz, CDCl3): δ 8.84 (br s., 1H), 8.13 (d, J = 4.8 Hz, 1H), 7.08 (br s, 1H), 6.82 (d, J =4.8 Hz, 1H), 3.07–3.11 (m, 2H), 2.70 (s, 3H), 2.65–2.69 (m, 2H), 2.39 (s, 6H). LCMS (ESI+): m / z 204.0. HPLC purity (220 nm): 99.6%.

[0343] N -Ethyl- N -Methyl-2-(4-methyl-1-methyl) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-31): Step 1 : N -Ethyl- N -Methyl-2-(5-methyl-1-methyl) H -pyrrolo[2,3- bPyridin-3-yl)ethyl-1-amine (P-31) To 3-(2-chloroethyl)-4-methyl-1 H -pyrrolo[2,3- b The product was stirred at 50 °C for 12 h with K₂CO₃ (160 mg, 1.16 mmol) and ethyl(methyl)amine (137 mg, 2.32 mmol) added to a solution of pyridine (150 mg, 771 µmol) in DMF (3 mL). The reaction mixture was then diluted with water (20 mL) and extracted with EtOAc (5 mL × 3). The combined organic matter was washed with brine (5 mL × 2), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm); mobile phase: [water (NH₄HCO₃)-ACN]; B: 10-40%, 9 min) to provide a grayish-white solid. N -Ethyl- N -Methyl-2-(5-methyl-1-methyl) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-31) (30.0 mg, 18%). 1 H NMR (400 MHz, CDCl3) δ 9.32 (br s, 1H), 8.13 (d, J = 4.8 Hz, 1H), 7.09 (s, 1H), 6.82 (d, J = 4.9 Hz, 1H), 3.07-3.11 (m, 2H), 2.69-2.73 (m, 2H), 2.71 (s, 3H), 2.57 (q, J = 7.1 Hz, 2H), 2.38 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H). LCMS (ESI+): m / z 218.0[M+H] + HPLC purity (220 nm): 96.7%.

[0344] N , N -Dimethyl-2-(4-fluoro-1- H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-32): Step 12-Chloro-1-(4-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (61) 4-Fluoro-1 H -pyrrolo[2,3- b The mixture of pyridine (700 mg, 5.14 mmol) in CH2Cl2 (15 mL) was degassed and purged three times with N2, followed by the addition of AlCl3 (3.43 g, 25.7 mmol) at 0 °C under N2 atmosphere. After stirring at 0 °C for 5 min, 2-chloroacetyl chloride (2.90 g, 25.7 mmol) was added at 0 °C, and the mixture was then stirred at ambient temperature under N2 atmosphere for 6 h. The reaction mixture was then cooled to 0 °C, quenched with water (20 mL), and adjusted to pH 9 with saturated Na2CO3 aqueous solution, followed by filtration. The filter cake was washed with EtOAc (30 mL × 4), and the aqueous phase was separated, diluted with water (30 mL), and extracted with EtOAc (20 mL × 3). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to provide crude 2-chloro-1-(4-fluoro-1-) as a yellow solid. H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl-1-one (61) (727 mg), the crude product was used for the next step without purification.

[0345] Step 2: 3-(2-Chloroethyl)-4-fluoro-1 H -pyrrolo[2,3- b Pyridine (62) To 2-chloro-1-(4-fluoro-1) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-one (700 mg) was added to a solution of TFA (10 mL) with Et3SiH (2.91 g, 25.0 mmol), and the reaction mixture was stirred at 25 °C for 12 hours. The reaction mixture was adjusted to pH 9 with saturated Na2CO3 aqueous solution, diluted with H2O (50 mL), and extracted with EtOAc (75 mL × 3). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was wet-milled at ambient temperature with 1:5 MTBE:petroleum ether (1:5 v / v, 20 mL) for 30 minutes and filtered to produce crude 3-(2-chloroethyl)-4-fluoro-1-one as a yellow solid. H -pyrrolo[2,3- bPyridine (62) (580 mg). LCMS (ESI+): m / z 199.1 [M+H] + .

[0346] Step 3: 2-(4-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N , N -Dimethylethyl-1-amine (P-32) To crude 3-(2-chloroethyl)-4-fluoro-1 H -pyrrolo[2,3- b Pyridine (200 mg) was added to a solution of DMF (5 mL) with K2CO3 (306 mg, 2.21 mmol) and THF containing 2 M dimethylamine (2.01 mL), and the solution was stirred in a sealed tube at 50 °C for 12 hours. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (20 mL × 5). The combined organic matter was washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm; mobile phase: [water (NH3)-ACN]; B: 18-48%, 10 min) to provide 2-(4-fluoro-1-ethylhexyl) as a yellow solid. H -pyrrolo[2,3- b ]pyridin-3-yl)- N,N -Dimethylethyl-1-amine (P-32) (34.1 mg, 10%, via 3 steps). 1 H NMR (400 MHz, CDCl3): δ 9.15 (brs, 1H), 8.21 (dd, J = 7.8, 5.5 Hz, 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 (400 MHz, CDCl3): δ -112.5. LCMS (ESI+): m / z 208.2 [M+H] + HPLC purity (220 nm): 96.6%.

[0347] N -Ethyl- N-Methyl-2-(4-fluoro-1- H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-33): Step 1 : N -Ethyl- N -Methyl-2-(4-fluoro-1- H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-33) To crude 3-(2-chloroethyl)-4-fluoro-1 H -pyrrolo[2,3- b Pyridine (200 mg) was added to a solution of K₂CO₃ (306 mg, 2.21 mmol) and ethyl(methyl)amine (238 mg, 4.03 mmol) in DMF (5 mL), and the solution 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 EtOAc (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 purified by preparative HPLC (column: Waters Xbridge (150 * 25 mm * 5 µm; mobile phase: [water (NH₃)-ACN]; B: 20-50%, 10 min) to provide a pink solid. N -Ethyl- N -Methyl-2-(4-fluoro-1- H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine (P-33, 34.1 mg, 9%, via 3 steps). 1 H NMR (400MHz, CDCl3): δ 9.25 (br s, 1H), 8.21 (dd, J = 7.7, 5.5 Hz, 1H), 7.10 (s, 1H), 6.77 (dd, J = 10.3, 5.5 Hz, 1H), 3.01-3.05 (m, 2H), 2.74-2.77 (m, 2H), 2.59(q, J = 7.0 Hz, 2H) 2.39 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H). 19F NMR (400 MHz, CDCl3): δ -112.4. LCMS (ESI+): m / z 222 [M+H] + HPLC purity (220 nm): 98.8%.

[0348] The following compounds S1 to S75 can be prepared via a similar route. Overview In the following examples, unless otherwise specified, temperatures are given in degrees Celsius (°C); operations are carried out at room temperature or ambient temperature “rt” or “RT” (typically in the range of about 18-25°C); solvent evaporation is carried out under reduced pressure (typically 4.5-30 mm Hg) using a rotary evaporator, with a bath temperature of no more than 60°C; the reaction process is typically followed by thin-layer chromatography (TLC); melting points are not corrected; and the products show satisfactory results. 1 1H NMR and / or trace analysis data; and also using the following common abbreviations: L (liter), mL (milliliters), mmol (millimoles), g (grams), mg (milligrams), min (minutes), and h (hours).

[0349] Unless otherwise specified, all solvents and reagents were purchased from the supplier and used without further purification. Unless otherwise specified, reactions were carried out under a nitrogen atmosphere. The compounds were visualized under a UV lamp (254 nm). Recordings were performed on a 300 MHz, 400 MHz, or 600 MHz NMR instrument as indicated. 1 ¹H NMR spectroscopy. Column chromatography and flash chromatography were performed using SiO₂ as the stationary phase, and "MeOH / NH₃" refers to a 9:1 solution of methanol and 15 M ammonia solution. LCMS was performed under the following conditions. Compounds of general formula (I) can be synthesized from a suitably substituted 6,5-aromatic system according to the steps outlined in schemes 5 and 6 below, or similar steps that a person skilled in the art might conceive of. Various substituted 6,5-aromatic systems are commercially available or can be prepared by techniques known in the art, for example, as described by Whelligan D et al. (Journal of Organic Chemistry, Vol. 75, January 1, 2010, pp. 11-15).

[0350] Compounds of general formula (I) can be synthesized from a suitably substituted 6,5-aromatic system by following the steps outlined in schemes 5 and 6 below or similar steps that a person skilled in the art might conceive of.

[0351] Option 5: Compounds of general formula (I) can be produced by appropriate substitution of 1 according to the sequence of steps outlined in Option 5 or a sequence of steps similar to that that a person skilled in the art might conceive of. H -pyrrolo[2,3- b Synthesis of pyridine systems. Amination of suitably 5-substituted 2-chloropyridines can be achieved via palladium-catalyzed cross-coupling with diphenylmethylimine, followed by hydrolysis under acidic conditions to yield Int. 1. Regioselective bromination allows alkynylation via Sonogashira coupling to provide Int. 3. Cyclization under basic conditions yields substituted 1. H -pyrrolo[2,3- b Pyridine (Int. 4) can be acylated using the Friedel-Crafts methodology. Reduction and subsequent nucleophilic substitution allow for the yield of compounds of general formula (I). Option 5 Option 6: Compounds of general formula (I) can be synthesized from alkyl halides according to the steps outlined in the following steps or similar steps that a person skilled in the art might conceive of. A primary amine intermediate can be obtained by Gabriel synthesis, which can then be successively reduced and alkylated with a desired carbonyl group and a reducing agent to provide a compound of general formula (I) (as illustrated in Example S30). Option 6 General Program A: 2-halogenated-1-(1 H -pyrrolo[2,3- b Preparation of pyridin-3-yl)acetone To the appropriate replacement 1 H -pyrrolo[2,3- bPyridine (1 equivalent) in anhydrous CH2Cl2 (5 mL / mmol 1 H -pyrrolo[2,3- b AlCl3 (3.5 equivalents) was added in portions to an ice-cold solution of pyridine. The reaction mixture was heated to reflux, and a solution of bromoacetyl bromide or chloroacetyl chloride (1 equivalent) in anhydrous CH2Cl2 (1 mL / mmol acyl halide) was added dropwise over 10 minutes. The reaction mixture was stirred under reflux for 1 hour, during which time it was cooled to room temperature and then poured onto ice. The crude product was obtained by filtration or extraction with EtOAc (3 x 10 V) and collection of the precipitate. The crude product was then purified by column chromatography (20% to 50% EtOAc / hexane) to obtain the desired compound.

[0352] General Procedure B: 2-Haloethyl-1 H -pyrrolo[2,3- b Preparation of pyridine 1 to be appropriately replaced H -pyrrolo[2,3- b A solution of pyridin-3-ylethyl ketone (1 equivalent) in Et3SiH (1 mL / mmol) and trifluoroacetic acid (1 mL / 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 (1.5 V). The combined organic matter was washed with brine, dried over Na2SO4 or MgSO4, filtered, and the filtrate was concentrated by rotary evaporation. The resulting crude aggregate was then purified by column chromatography (0% to 10% EtOAc / hexane) to obtain the desired compound.

[0353] General Procedure C: Using free alkaline amines to make 2-haloethyl-1 H -pyrrolo[2,3- b ]Pyridine alkylation.

[0354] Add a suitably substituted amine (3 equivalents) to a pressure tube containing a suitably substituted alkyl halide (1 equivalent) and NaI (1 equivalent) in DMF (2 mL / mmol), and heat the sealed container to 70 °C until complete. Cool the reaction mixture, pour it into H₂O (10 V), dilute with saturated Na₂CO₃ aqueous solution (5 V), and adjust the pH to 12 dropwise with 15% NaOH aqueous solution. Extract with EtOAc (3 x 10 V). Wash the combined organic matter subsequently with saturated Na₂CO₃ aqueous solution (5 x 2 V), H₂O (1 x 2 V), and brine (2 x 4 V), then dry (Na₂SO₄ or MgSO₄), filter, and concentrate the filtrate under reduced pressure. Purify the resulting crude agglomerate by column chromatography (0.1% to 10% MeOH / NH₃ / CH₂Cl₂) to obtain the desired product.

[0355] General Procedure D: Using amine hydrochloride to make 2-haloethyl-1 H -pyrrolo[2,3- b ]Pyridine alkylation.

[0356] Add the appropriate substituted amine hydrochloride (1.3–1.5 equivalents) to a pressure tube containing a solution of a suitably substituted alkyl halide (1 equivalent) and NaI (1 equivalent) in DMF (2 mL / mmol). i Pr2NEt (3 equivalents) and heat the sealed container to 70°C until complete. Then cool the reaction mixture, pour it into H2O (10 V), dilute with saturated Na2CO3 aqueous solution (5 V), and adjust the pH to 12 dropwise with 15% NaOH aqueous solution. Extract with EtOAc (3 x 10 V). The combined organic matter was then washed with saturated Na2CO3 aqueous solution (5 x 2 V), H2O (1 x 2 V), and brine (2 x 4 V), dried (Na2SO4 or MgSO4), filtered, and the filtrate concentrated under reduced pressure. The resulting crude agglomerate was then purified by column chromatography (0.1% to 10% MeOH / NH3 / CH2Cl2) to obtain the desired product.

[0357] General Procedure E: Preparation of hydrochloride from amines Dissolve the initial free alkali amine in a minimal amount of solvent (MeOH, i The product was added to PrOH or a mixture thereof and acidified to pH 1 by dropwise addition of concentrated HCl (37%). Precipitation was initiated by adding Et2O, and the mixture was allowed to stand at 0°C. The product was collected by vacuum filtration and washed with Et2O.

[0358] General Procedure F: Formulating fumarate and maleate from amines Free alkali amine in a minimum amount of solvent (acetone or i A solution of PrOH is added to fumaric acid or maleic acid in acetone or i The mixture was placed in a hot solution of PrOH (1–3 equivalents, 0.02–0.2 M) and heated to 40–60 °C. The mixture was cooled and precipitation was initiated by adding Et₂O or hexane, and then allowed to stand at 0 °C. The product was collected by vacuum filtration and washed with Et₂O.

[0359] Example 1: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N Synthesis of methylcyclopropylamine (S1): Step 1: 2-Bromo-1-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-one (64) According to general procedure A, 5-fluoro-1 H -pyrrolo[2,3- b The title compound was synthesized from pyridine (2.28 g, 16.7 mmol) to give the title compound (2.2 g, 51%) as a light brown solid. 1 H NMR (400 MHz, CDCl3): δ 10.22 (s, 1H), 8.45 (dd, J = 8.5, 2.7 Hz, 1H), 8.34 - 8.28 (m, 1H), 8.18 (s, 1H), 4.31 (s, 2H).

[0360] Step 2: 3-(2-Bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (65) According to general procedure B, 2-bromo-1-(5-fluoro-1) H -pyrrolo[2,3- b The title compound was synthesized from pyridin-3-yl)ethyl-1-one (1 g, 3.9 mmol) to give the title compound (0.8 g, 85%) as white crystalline needles. 1 H NMR (400MHz, DMSO- d 6): δ11.64 (s, 1H), 8.24 - 8.12 (m, 1H), 8.00 - 7.90 (m, 1H),7.49 (d, J = 2.6 Hz, 1H), 3.75 (t, J = 7.3 Hz, 2H), 3.23 (td, J = 7.3, 0.8Hz, 2H); 13 C NMR (101 MHz, DMSO- d 6): δ 155.3 (d, J = 238.4 Hz), 145.8, 131.1 (d, J = 29.0 Hz), 127.2, 119.6 (d, J = 6.9 Hz), 112.9 (d, J = 20.6 Hz), 111.5(d, J = 4.3 Hz), 34.7, 29.0.

[0361] Step 3: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N 1-Methylcyclopropylamine hydrochloride (S1·HCl) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.4 g, 1.65 mmol), N -Methylcyclopropylamine hydrochloride (266 mg, 2.5 mmol) and i The title compound was synthesized using Pr2NEt (0.86 mL, 4.9 mmol), and purified to yield a colorless oil (293 mg, 76%). This oil was then reconstituted into a white crystalline solid hydrochloride (180 mg, 54%) according to general procedure E. LCMS (Condition A): t R (3.210 minutes) m / z = 234.15[M+H] + ; 1 H NMR (400 MHz, DMSO- d 6): δ 11.69 (s, 1H), 10.78 (s, 1H), 8.21 (dd, J= 2.8, 1.7 Hz, 1H), 8.02 (dd, J = 9.6, 2.8 Hz, 1H), 7.51 (d, J = 2.5 Hz, 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 (101 MHz, DMSO- d 6): δ 155.2 (d, J = 238.6 Hz), 145.9, 131.5, 127.0, 119.5 (d, J = 6.9 Hz), 112.9(d, J = 20.7 Hz), 109.1, 56.6, 41.3, 39.1, 20.4, 5.5, 3.6.

[0362] Example 2: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b Synthesis of pyridin-3-yl)ethyl)cyclopropylamine (S2): Step 1: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)cyclopropylamine fumarate (S2·fumarate) Cyclopropylamine (0.13 mL, 1.81 mmol) was added to 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- bPyridine (0.2 g, 0.82 mmol) was dissolved in DMF (5 mL). This solution was heated to 80 °C in a pressure tube for 4 hours. The reaction mixture was then cooled and poured into H2O (50 mL), followed by extraction with EtOAc (3 x 20 mL). The combined organic matter was washed successively with H2O (3 x 100 mL) and brine (1 x 100 mL), dried over (MgSO4), filtered, and concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 / CH2Cl2) to give the title compound as a colorless oil, which was then reconstituted into a white crystalline solid fumarate (115 mg, 39%) according to general procedure F. LCMS (condition A): t R (3.162 minutes) m / z = 220.10 [M+H] + ; 1 H NMR (400MHz, DMSO- d 6): δ 11.56 (s, 1H), 8.16 (dd, J = 2.6, 1.8 Hz, 1H), 7.88 (dd, J =9.6, 2.7 Hz, 1H), 7.42 (d, J = 2.4 Hz, 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).

[0363] Example 5: Synthesis N -Cyclopropyl- N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)cyclopropylamine (S5): Step 1: N -Cyclopropyl- N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)cyclopropylamine hydrochloride (S5·HCl) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- bPyridine (0.2 g, 0.82 mmol), N - Cyclopropylcyclopropylamine hydrochloride (143 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol) and i The title compound was synthesized using Pr2NEt (0.43 mL, 2.46 mmol), and after purification, it yielded a colorless oily substance, which was then prepared into a white crystalline solid hydrochloride (85 mg, 35%) according to general procedure E. LCMS (condition A): t R (3.504 minutes) m / z = 260.10 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6): δ 11.72 (s, 1H), 10.89 (s,1H), 8.30 - 8.12 (m, 1H), 8.01 (dd, J = 9.5, 2.7 Hz, 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); 13 C NMR (101 MHz, DMSO- d 6): δ 154.7 (d, J = 238.7 Hz), 145.3, 130.8 (d, J = 29.1 Hz), 126.6, 119.1 (d, J = 6.8 Hz), 112.5 (d, J = 20.7 Hz), 108.9 (d, J = 4.4 Hz), 56.5, 38.1, 19.8, 3.4, 3.2.

[0364] Example 6: Synthesis of 5-fluoro-3-(2-(pyrrolidone-1-yl)ethyl)-1 H -pyrrolo[2,3- b Pyridine (S6): Step 1:5-Fluoro-3-(2-(pyrrolidone-1-yl)ethyl)-1 H -pyrrolo[2,3- b Pyridine fumarate (S6·fumarate) Pyrrolidine (0.15 mL, 1.81 mmol) was added to 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.2 g, 0.82 mmol) was dissolved in DMF (5 mL). This solution was heated to 80 °C in a pressure tube for 4 hours. The reaction mixture was then cooled and poured into H2O (50 mL), followed by extraction with EtOAc (3 x 20 mL). The combined organic matter was washed successively with H2O (3 x 100 mL) and brine (1 x 100 mL), dried over (MgSO4), filtered, and concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 / CH2Cl2) to give the title compound as a colorless oil, which was then reconstituted into a white crystalline solid fumarate (120 mg, 53%) according to general procedure F. LCMS (condition A): t R (3.114 minutes) m / z = 234.10 [M+H] + ; 1 H NMR (400MHz, DMSO- d 6): δ 11.59 (s, 1H), 8.18 (dd, J = 2.8, 1.7 Hz, 1H), 7.93 (dd, J =9.7, 2.8 Hz, 1H), 7.44 (d, J = 2.5 Hz, 1H), 6.53 (s, 2H), 3.11 - 3.05 (m, 2H), 3.05 - 2.93 (m, 6H), 1.88 - 1.80 (m, 4H).

[0365] Example 7: Synthesis of 5-fluoro-3-(2-(piperidin-1-yl)ethyl)-1 H -pyrrolo[2,3- b Pyridine (S7): Step 1: 5-Fluoro-3-(2-(piperidin-1-yl)ethyl)-1 H -pyrrolo[2,3- bPyridine fumarate (S7·fumarate) Piperidine (0.18 mL, 2.2 equivalents, 1.81 mmol) was added to 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.2 g, 0.82 mmol) was dissolved in DMF (5 mL). This solution was heated to 80 °C in a pressure tube for 4 hours. The reaction mixture was then cooled and poured into H2O (50 mL), followed by extraction with EtOAc (3 x 20 mL). The combined organic matter was washed successively with H2O (3 x 100 mL) and brine (1 x 100 mL), dried over (MgSO4), filtered, and the filtrate was concentrated under reduced pressure. The resulting oil was purified by column chromatography (1-10% MeOH / NH3 / CH2Cl2) to give the title compound as a colorless oil, which was then reconstituted into a white crystalline solid fumarate (110 mg, 37%) according to general procedure F. LCMS (condition A): t R (3.315 minutes) m / z = 248.15 [M+H] + ; 1 HNMR (400 MHz, DMSO- d 6): δ 11.56 (s, 1H), 8.17 (dd, J = 2.8, 1.7 Hz, 1H), 7.90(dd, J = 9.7, 2.8 Hz, 1H), 7.42 (d, J = 2.5 Hz, 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).

[0366] Example 8: Synthesis of 3-(2-(1-azaspiro[3.3]hept-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (S8): Step 1: 3-(2-(1-azaspiro[3.3]hept-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine hydrochloride (S8·HCl) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -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 i The title compound was synthesized using Pr2NEt (0.43 mL, 2.46 mmol), and after purification, it yielded a pale yellow oily substance, which was then reconstituted into a brown solid hydrochloride (109 mg, 45%) according to general procedure E. LCMS (condition A): t R (3.493 minutes) m / z = 260.10 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6): δ 11.70 (s, 1H),10.71 (s, 1H), 8.20 (dd, J = 2.8, 1.7 Hz, 1H), 8.06 - 7.98 (m, 1H), 7.51 (d, J = 2.5 Hz, 1H), 3.97 - 3.70 (m, 2H), 3.50 - 3.41 (m, 1H), 3.25 - 3.11 (m,1H), 3.03 - 2.91 (m, 2H), 2.66 (q, J = 10.5 Hz, 1H), 2.61 - 2.45 (m, 3H), 2.18 - 2.06 (m, 2H), 1.84 - 1.66 (m, 2H).

[0367] Example 9: Synthesis of 3-(2-(azacyclobutane-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (S9): Step 1: 3-(2-(azacyclobutane-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (S9) According to general procedure C, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- bThe title compound was synthesized from pyridine (0.5 g, 2.06 mmol) and aziridine (0.69 mL, 10.3 mmol), but MeCN was used instead of DMF as the solvent. After purification, the title compound was a yellow solid (230 mg, 44%). 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.45(s, 1H), 8.19 - 8.05 (m, 1H), 7.81 (dd, J = 9.7, 2.8 Hz, 1H), 7.43 - 7.25 (m,1H), 3.08 (t, J = 6.9 Hz, 4H), 2.67 - 2.54 (m, 4H), 1.93 (p, J = 6.9 Hz, 2H).

[0368] Step 2: 3-(2-(azacyclobutane-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine fumarate (S9·fumarate) According to general procedure F, 3-(2-(azacyclobutan-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (430 mg, 1.96 mmol) was reconstituted into fumarate (540 mg, 82%) as a grayish-white solid. LCMS (Condition A): t R (2.999 minutes) m / z = 220.10 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.59 (s,1H), 8.20 - 8.08 (m, 1H), 7.92 (dd, J = 9.7, 2.7 Hz, 1H), 7.41 (d, J = 2.4Hz, 1H), 6.53 (s, 2H), 3.69 (t, J = 7.7 Hz, 4H), 3.14 - 3.04 (m, 2H), 2.85 -2.74 (m, 2H), 2.18 (p, J= 7.7 Hz, 2H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 167.6,154.8 (d, J = 238.3 Hz), 145.5, 134.9, 130.6 (d, J = 28.9 Hz), 126.4, 119.2 (d, J = 6.8 Hz), 112.4 (d, J = 20.6 Hz), 109.6, 55.8, 53.5, 21.2, 16.4; 1 HqNMR purity: 99.2% (ERETIC).

[0369] Example 11: Synthesis N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)cyclobutamine (S11): Step 1: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b Pyridin-3-yl)ethyl)cyclobutylamine maleate (S11 maleate) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.2 g, 0.82 mmol), cyclobutanamine hydrochloride (115 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol) and i The title compound was synthesized using Pr2NEt (0.43 mL, 2.46 mmol), and after purification, it yielded a colorless oily substance, which was then reconstituted into a white crystalline solid 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 (400 MHz, DMSO- d 6): δ 11.69 (s, 1H), 8.54 (s, 1H), 8.33- 8.12 (m, 1H), 7.91 (dd,J = 9.6, 2.8 Hz, 1H), 7.48 (d, J = 2.5 Hz, 1H), 6.02 (s, 2H), 3.73 (p, J = 8.0 Hz, 1H), 3.09 (t, J = 7.4 Hz, 2H), 2.97 (t, J = 7.5 Hz, 2H), 2.27 - 2.01 (m, 4H), 1.86 - 1.68 (m, 2H); 13 C NMR (101 MHz, DMSO- d 6): δ 167.2, 154.8 (d, J = 238.5 Hz), 145.5, 136.1, 130.8 (d, J = 28.9Hz), 126.9, 119.1 (d, J = 6.8 Hz), 112.3 (d, J = 20.7 Hz), 108.4 (d, J = 4.4Hz), 50.8, 44.3, 26.0, 21.8, 14.5.

[0370] Example 12: Synthesis N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N -Methylcyclobutanamine (S12): Step 1: N -(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl)- N 1-Methylcyclobutylamine hydrochloride (S12·HCl) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -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 iThe title compound was synthesized using Pr2NEt (0.43 mL, 2.46 mmol), and after purification, it yielded a pale yellow oil. This oil was then prepared as a colorless solid hydrochloride (192 mg, 73%) according to general procedure E. LCMS (Condition A): t R (3.895 minutes) m / z = 300.15 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.71 (s, 1H), 11.07 (s,1H), 8.31 - 8.13 (m, 1H), 8.03 (dd, J = 9.6, 2.7 Hz, 1H), 7.51 (d, J = 2.5Hz, 1H), 3.78 - 3.60 (m, 1H), 3.30 - 2.96 (m, 4H), 2.69 (d, J = 5.0 Hz, 3H),2.46 - 2.27 (m, 2H), 2.27 - 2.07 (m, 2H), 1.82 - 1.53 (m, 2H); 13 C NMR (101MHz, DMSO- d 6 ): δ 154.8 (d, J = 238.8 Hz), 145.3, 130.8 (d, J = 29.0 Hz), 126.7, 119.2 (d, J = 7.3 Hz), 112.6 (d, J = 21.3 Hz), 108.7 (d, J = 4.4 Hz), 58.5, 52.0, 35.6, 25.5, 25.1, 19.6, 13.0.

[0371] Example 15: Synthesis of 4-(2-(5-fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)morpholine (S15): Step 1: 4-(2-(5-fluoro-1) H -pyrrolo[2,3-b ]pyridin-3-yl)ethyl)morpholine (S15) According to general procedure C, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b The title compound was synthesized from pyridine (0.2 g, 0.82 mmol), morpholine (0.21 mL, 2.47 mmol), and NaI (123 mg, 0.82 mmol), and purified to yield the title compound as a white solid (180 mg, 88%). LCMS (condition A): t R (2.954 minutes) m / z = 250.15[M+H] + ; 1 H NMR (400 MHz, DMSO- d 6): δ 11.48 (s, 1H), 8.20 - 8.10 (m, 1H), 7.84(dd, J = 9.7, 2.7 Hz, 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 (101 MHz, DMSO- d 6): δ 154.7(d, J = 238.1 Hz), 145.4, 130.3 (d, J = 28.9 Hz), 125.8, 119.6 (d, J = 6.7Hz), 112.3 (d, J = 20.5 Hz), 112.0 (d, J = 4.3 Hz), 66.3, 58.8, 53.3, 22.0.

[0372] Example 16: 3-(2-(2-methylazacyclobutane-1-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Synthesis of pyridine (S16): Step 1: 3-(2-(2-methylazacyclobutane-1-yl)ethyl)-5-fluoro-1 H-pyrrolo[2,3-b]pyridine hydrochloride (S16·HCl) According to general procedure D, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.2 g, 0.82 mmol), 2-methylazacyclobutane hydrochloride (115 mg, 1.07 mmol), NaI (123 mg, 0.82 mmol) and i The title compound was synthesized using Pr2NEt (0.43 mL, 2.46 mmol), and after purification, it yielded a pale yellow oily substance, which was then reconstituted into a grayish-white solid hydrochloride (94 mg, 42%) according to general procedure E. LCMS (condition A): t R (3.127 minutes) m / z = 234.15 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.70 (s, 1H), 10.88 (s,1H), 8.20 (dd, J = 2.5, 1.8 Hz, 1H), 8.04 (dd, J = 9.6, 2.6 Hz, 1H), 7.48 (d, J = 2.5 Hz, 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 = 6.6 Hz, 3H).

[0373] Example 17: Synthesis N -(cyclopropylmethyl)-2-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-amine (S17): Step 1: N -(cyclopropylmethyl)-2-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-amine (S17) According to general procedure C, 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.2 g, 0.82 mmol), N The title compound was synthesized from (cyclopropylmethyl)amine (0.21 mL, 2.47 mmol) and NaI (123 mg, 0.82 mmol), and purified to produce the title compound (150 mg, 78%) as a pale yellow oil. 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.48 (s, 1H), 8.14 (dd, J = 2.7, 1.7 Hz, 1H), 7.83 (dd, J = 9.7, 2.7 Hz,1H), 7.36 (s, 1H), 2.84 - 2.73 (m, 4H), 2.40 (d, J = 6.6 Hz, 2H), 0.95 - 0.77(m, 1H), 0.45 - 0.29 (m, 2H), 0.13 - -0.02 (m, 2H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.7 (d, J = 238.1 Hz), 145.5, 130.3 (d, J = 28.9 Hz), 125.8, 119.6 (d, J = 6.6 Hz), 112.3 (d, J = 18.2 Hz), 112.2 (d, J = 2.1 Hz), 54.0, 49.8,25.5, 11.2, 3.2.

[0374] Step 2: N -(cyclopropylmethyl)-2-(5-fluoro-1 H -pyrrolo[2,3- b Pyridin-3-yl)ethyl-1-amine hydrochloride (S17·HCl) According to general procedure E, N -(cyclopropylmethyl)-2-(5-fluoro-1 H -pyrrolo[2,3- bPyridin-3-yl)ethyl-1-amine (140 mg, 0.60 mmol) was prepared as a grayish-white solid hydrochloride (77 mg, 48%). LCMS (Condition A): t R (3.348 minutes) m / z = 234.15 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.73 (s, 1H),9.21 (s, 2H), 8.24 - 8.16 (m, 1H), 8.04 (dd, J = 9.6, 2.7 Hz, 1H), 7.49 (d, J = 2.5 Hz, 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). 13 C NMR (101 MHz, DMSO- d 6 ): δ 154.7(d, J = 238.5 Hz), 145.2, 130.5 (d, J = 29.2 Hz), 126.8, 119.4 (d, J = 6.8Hz), 112.8 (d, J = 20.8 Hz), 109.0 (d, J = 4.3 Hz), 51.1, 46.5, 41.9, 21.6,7.0, 4.0. 1 ¹H qNMR purity: 92.9% (ERETIC).

[0375] Example 25: Synthesis of 3-(2-(2-azabicyclo[3.1.0]hex-2-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (S25): Step 1: 3-(2-(2-azabicyclo[3.1.0]hex-2-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3-b Pyridine (S25) 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b A solution of pyridine (250 mg, 1.03 mmol) in acetonitrile (5 mL) was prepared with 2-azabicyclo[3.1.0]hexane hydrochloride (246 mg, 2.06 mmol) and i The mixture was treated with Pr₂NEt (0.9 mL, 5.14 mmol) and stirred at room temperature for 48 hours. The solution was diluted with a semi-saturated NH₄Cl aqueous solution (100 mL) and extracted with CH₂Cl₂ (25 mL x 3), followed by... i Extracted with PrOH:CHCl3 (1:3, 25 mL x 3). The combined organic layers were concentrated and the residue was purified by flash chromatography (1% to 8% MeOH / NH3 / CH2Cl2) to yield the title compound (210 mg, 83%) as a grayish-white solid. 1 H NMR (400 MHz, CDCl3): δ 9.43(s, 1H), 8.20 - 8.01 (m, 1H), 7.63 (ddd, J = 8.9, 2.8, 0.6 Hz, 1H), 7.24 (d, J = 2.3 Hz, 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, 6.9 Hz, 1H), 1.58 - 1.47 (m, 1H), 0.71 (ddd, J =6.6, 4.3, 2.7 Hz, 1H), 0.20 (dt, J = 8.1, 5.9 Hz, 1H); 13 C NMR (101 MHz, CDCl3): δ 155.6 (d, J = 241.4 Hz), 145.7, 131.6 (d, J = 29.5 Hz), 124.5, 120.2 (d, J = 6.3 Hz), 113.1, 113.0 (d, J= 20.5 Hz), 55.1, 48.8, 40.7, 26.8,25.1, 15.4, 2.0.

[0376] Step 2: 3-(2-(2-azabicyclo[3.1.0]hex-2-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine fumarate (S25·fumarate) According to general procedure F, 3-(2-(2-azabicyclo[3.1.0]hex-2-yl)ethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (185 mg, 0.75 mmol) was reconstituted into a white solid fumarate (162 mg, 59%). LCMS (Condition A): t R (3.216 minutes) m / z = 246.15 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6 ): δ 11.55 (s, 1H), 8.16 (dd, J = 2.6, 1.8 Hz, 1H), 7.88 (dd, J = 9.7, 2.7 Hz, 1H), 7.43(d, J = 2.5 Hz, 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, 2.6 Hz, 1H), 0.30 (dt, J = 8.1, 6.1 Hz, 1H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 167.1, 154.7 (d, J = 238.3 Hz),145.5, 134.6, 130.5 (d,J = 28.9 Hz), 126.1, 119.4 (d, J = 6.8 Hz), 112.4 (d, J = 20.5 Hz), 110.8 (d, J = 4.4 Hz), 53.8, 47.8, 40.0, 25.8, 23.3, 14.9, 2.2; 1 H qNMR purity: 100% (ERETIC).

[0377] Example 30: 2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N-(2-Fluorobenzyl)ethyl Synthesis of -1-amine (S30). Step 1: 2-(2-(5-Fluoro-1) H -pyrrolo[2,3- b ]Pyridin-3-yl)ethyl)isoindole-1,3-dione (66).

[0378] Potassium phthalimide (1.01 g, 4.95 mmol) was added to 3-(2-bromoethyl)-5-fluoro-1 H -pyrrolo[2,3- b Pyridine (0.8 g, 3.29 mmol) was dissolved in DMF (5 mL). This solution was heated to 80 °C in a pressure tube for 4 hours. The reaction mixture was then cooled and poured into H2O (50 mL), followed by extraction with EtOAc (3 x 20 mL). The combined organic compounds were washed successively with H2O (3 x 100 mL) and brine (1 x 100 mL), dried over (MgSO4), and concentrated under reduced pressure. The resulting oil was purified by column chromatography (10% MeOH / CH2Cl2) to give the desired compound as a yellow solid.

[0379] Step 2: 2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)ethyl-1-amine (S29).

[0380] To 2-(2-(5-fluoro-1) H -pyrrolo[2,3- bHydrazine-3-yl)ethyl)isoindoline-1,3-dione (800 mg, 2.59 mmol) was added to a solution of EtOH (10 mL) with hydrazine monohydrate (1.25 mL, 25.9 mmol), 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 / CH2Cl2) to yield the title compound. 1 H NMR (400 MHz, DMSO- d 6): δ 8.19 - 8.06 (m, 1H), 7.83 (dd, J = 9.7, 2.8 Hz, 1H), 7.35 (s, 1H), 3.17 (s, 2H), 2.85 - 2.76 (m, 2H), 2.76 - 2.64 (m, 2H).

[0381] Step 3: 2-(5-Fluoro-1) H -pyrrolo[2,3- b ]pyridin-3-yl)- N -(2-Fluorobenzyl)ethyl-1-amine (S30).

[0382] At 0°C, 2-(...

Claims

1. A compound of formula (I): （I） Or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug. in R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 2 Independently selected from hydrogen and C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Alternatively, R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; R 3 Selected from hydrogen, C 1-6 Alkyl, C 3-8 cycloalkyl or C 4-14 alkylenecycloalkyl; Alternatively, R 3 and R 1 and R 2 One of them combines with the atoms it is attached to to form C 3-12 Heterocyclic alkyl groups The C 3-12 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 ; Each R 4 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-7 cycloalkyl and C 3-7 Heterocyclic alkyl, the C 3-7 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 , The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-7 cycloalkyl and the C 3-7 Each heterocyclic alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C3-C7 cycloalkyl group and the C 3-7 Each heterocyclic alkyl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 5 ; Each R 5 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 5-10 Heterocyclic alkyl, C 6-12 Aryl and C 5-10 Mixed aromatics, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 5-10 Heterocyclic alkyl groups, the C 6-12 Aryl and the C 5-10 Each of the heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3; R 7 R 8 R 9 R 10 and R 11 Each is independently selected from hydrogen, halogen, CN, OR 13 、N(R 13 2. SR 13 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C2-C6 haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-6 Alkylamine, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, 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 OC(O)N(R) 13 2. OS(O)R 13 OS(O)N(R) 13 2. OSO2R 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. 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 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl, C 4-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C2-C6 haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 1-6 Alkylamine, the C 1-6 Alkoxy, the C 1-6 Haloalkoxy groups, the C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 The alkylene heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 3-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 4-16 Each of the alkylene heteroaryl groups is further optionally substituted by one or more substituents selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 13 ; Each R 13 Independently selected from hydrogen and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylenecycloalkyl, C 3-10 Heterocyclic alkyl, C 4-16 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl group, the C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C 3-10 Heterocyclic alkyl groups, the C 4-16 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, CN, C. 1-8 Alkoxy, C 1-8 Alkylamino, C 1-8 Alkyl sulfonyl, 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 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heteroalkyl groups include one or two cyclic heteromers selected from the following: O, S, S(O), SO2, N, NH and NCH3.

2. The compound of claim 1 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 9 Independently selected from halogens, CN, -OH, C 1-6 Haloalkyl, C 1-6 Alkoxy and C 1-6 Halogenated alkoxy groups, The C 1-6 Halogenated alkyl groups, the C 1-6 alkoxy groups and the C 1-6 The haloalkoxy group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 .

3. The compound of claim 2 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 9 Selected from halogenated, CN, -OH, C 1-4 Alkoxy, C 1-4 Halogenated alkoxy groups and C 1-4 Halogenated alkyl groups.

4. The compound of claim 3 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 9 Selected from fluorine, chlorine, bromine, CN, -OH, methoxy, trifluoromethoxy, and trifluoromethyl.

5. The 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, wherein R 7 For H, R 8 For H, and R 10 H is provided, and the compound is provided by formula (II): (II)。 6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 2-6 alkenyl, the C 2-6 Haloalkenyl, the C 2-6 alkynyl group, the C 2-6 Halogenated alkynyl group, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

7. The 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, wherein R 1 Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, The C 1-6 Alkyl, the C 1-6 Each haloalkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, 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 .

8. The 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, wherein R 2 Selected independently from C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 4-14 alkylene cycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 alkylene heterocyclic alkyl, C 6-12 Aryl, C 7-18 alkylene aryl, C 5-10 heteroaryl and C 6-16 alkylene heteroaryl, The C 1-6 Halogenated alkyl groups, the C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each of the alkylene heteroaryl groups is optionally substituted by one or more substituents independently selected from the following: halogen, 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 , The C 3-8 cycloalkyl, the C 4-14 alkylenecycloalkyl, the C3-C8 heterocycloalkyl, the C4-C 14 alkylene heterocyclic alkyl, the C 6-12 Aryl, the C 7-18 alkylene aryl, the C 5-10 heteroaryl and the C 6-16 Each alkylene heteroaryl group is further optionally substituted by one or more substituents independently selected from the following: (O), C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

9. The 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, wherein R 1 and R 2 Together with the atoms it is attached to, they form C 3-8 Heterocyclic alkyl, the C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 , The C 3-8 The heterocyclic alkyl group is further optionally substituted by one or more substituents selected from: halogen, (O), 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 SO2R 4 C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 Haloalkenyl, C 2-6 alkynyl group, C 2-6 Halogenated alkynyl group, C 1-8 Alkylamino, C 1-8 alkylsulfonyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

10. The compound of claim 9 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 1 and R 2 Together they form C 4-8 Heterocyclic alkyl, the C 4-8 Heterocyclic alkyl groups include 0 or 1 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 Wherein C 4-8 The heterocyclic alkyl group is optionally substituted by one or more substituents selected from the following: halogen, C 1-8 Alkoxy, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 3-6 Heterocyclic alkyl, the C 3-6 Heterocyclic alkyl groups include one or two cyclic heteromers selected from the following: O, S, N, S(O), SO2, and NR. 4 .

11. The compound according to claim 9 or 10, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 1 and R 2 Together with the nitrogen atom it is attached to, they form C 4-8 Heterocyclic alkyl, the C 4-8 Heterocyclic alkyl groups do not include additional heterocyclic moieties.

12. The compound according to any one of claims 9 to 11, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 1 and R 2 Together with the nitrogen atom it is attached to, it forms a bicyclic C 6-8 Heterocyclic alkyl groups.

13. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein: R 1 Independently selected from hydrogen, or optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Halogenated alkyl groups, optionally substituted C 3-8 cycloalkyl, optionally substituted C 4-14 Alkylene cycloalkyl, optionally substituted C3-C8 heterocyclic alkyl, optionally substituted C4-C 14 alkylene heterocyclic alkyl, optionally substituted C 6-12 aryl, optionally substituted C 7-18 alkylene aryl, optionally substituted C 5-10 Heteroaryl and optionally substituted C 6-16 alkylene heteroaryl, and R 2 Independently selected from the arbitrarily substituted C 3-8 cycloalkyl, optionally substituted C 4-14 Alkylene cycloalkyl, optionally substituted C3-C8 heterocyclic alkyl, optionally substituted C4-C 14 alkylene heterocyclic alkyl, optionally substituted C 6-12 aryl, optionally substituted C 7-18 alkylene aryl, optionally substituted C 5-10 Heteroaryl and optionally substituted C 6-16 alkylene heteroaryl, Alternatively, R 1 and R 2 Together with the atoms they are attached, they form optionally substituted C atoms. 3-8 Heterocyclic alkyl groups, the optionally substituted C 3-8 Heterocyclic alkyl groups include 0, 1, or 2 additional cyclic heteromers selected from the following: O, S, S(O), SO2, N, and NR. 4 .

14. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein R 1 and R 2 Together with the nitrogen it is attached to, it forms any of the following: -NH2、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

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

16. The compound according to claim 1, wherein the compound is selected from: Or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug.

17. A medicament comprising the compound of 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, and a pharmaceutically acceptable excipient.

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

20. A method for treating a mental illness, the method comprising administering to a subject in need 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 medicament according to claim 17; or a pharmaceutical composition according to claim 18.

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

22. A method for increasing neuronal plasticity and / or increasing dendritic spine density, the method comprising contacting a neuronal cell with: The 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; The medicament according to claim 17; or the pharmaceutical composition according to claim 18.

23. 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, for the preparation of a medicament for use in one or more of the following: ● Treating diseases, conditions, or symptoms by activating serotonin receptors; and / or ● Treatment of mental illness; and / or ● Treatment of diseases, conditions, or symptoms of the central nervous system (CNS) and / or diseases, conditions, or symptoms of the nervous system; and / or ●Increase neuronal plasticity and / or increase dendritic spine density.

Images