Compound

Abstract

The present disclosure relates generally to compounds, methods for their synthesis, and their use in treating psychiatric or central nervous system disorders.

Description

[Technical Field]

[0001] This application claims priority to Australian Provisional Application No. 2021 / 904268 (filed December 24, 2021), the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to novel compounds, methods for their synthesis, and their use in treating psychiatric or central nervous system disorders. [Background technology]

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

[0004] A variety of serotonergic medications, including antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors, are commercially available to treat psychiatric disorders. Unfortunately, in many indications, these medications offer limited benefit compared to placebo. Additionally, these medications can result in a wide range of side effects, including loss of libido, insomnia, fatigue, and weight gain. Despite their limited efficacy, these medications continue to be used to treat neuropsychiatric conditions and a wide range of adjunctive medical indications. Since the launch of many of these medications, progress in new treatment options has been limited, and the pharmaceutical industry is facing increasing financial pressure to fully deemphasize neuroscience programs. There is a growing unmet need for more effective mental health treatments, and the global COVID-19 pandemic may increase the burden of disease worldwide.

[0005] The use of psychedelic drugs to treat various mental illnesses was widely studied in the 1950s and 1960s, and these substances showed promise as treatments for many disorders of the central nervous system (CNS). After decades of prohibition, scientific research into the application of psychedelics as treatments for mental illness is gaining momentum. The serotonergic psychedelic agent psilocybin has been designated a breakthrough therapy by the FDA for the treatment of major depressive disorder (2019) and treatment-resistant depression (2018). Psilocybin is a prodrug compound produced by many species of mushrooms collectively known as psilocybin mushrooms or "magic mushrooms." Psilocybin is rapidly metabolized into the bioactive compound psilocin, which produces states of altered consciousness, including altered perceptions, visual hallucinations, and distorted senses of space, time, and self. Many patients report spiritual or "mystical" experiences that have profound and lasting effects on their mood and behavior. Psilocybin has shown promise in over 50 clinical trials for neuropsychiatric indications, including numerous anxiety disorders, obsessive-compulsive disorder, anorexia nervosa, alcoholism, and tobacco dependence. Psilocybin, as well as other psychedelic compounds such as N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), have both immediate and persistent effects on mental state, the latter continuing well beyond the duration of action, likely as a result of their ability to induce increased neuroplasticity in the brain, promote neuronal proliferation, and increase spine density of synaptic neurons.

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

[0007] Despite their therapeutic potential, psilocybin and other psychedelics remain scheduled as drugs of abuse in most countries, and the commercial path to market for these drugs as medicines is uncertain. As adjuncts to psychotherapy, the long duration of action of psilocybin and LSD makes treatment sessions expensive and impractical for widespread implementation. Despite a long history of safe human use, several adverse events have been reported in clinical trials, which may be attributed to signaling bias at the 5-HT2A (primary target) or off-target activity at, for example, the 5-HT2B receptor (cardiac liability antitarget), the 5-HT1A (anxiolytic target), or the 5-HT2C receptor (disease-associated target, e.g., obesity and some genetic epilepsies). Naturally occurring psychedelics provide important leads for a new generation of neurotherapeutics with novel mechanisms of action and / or superior clinical efficacy to currently available neuropsychiatric drugs.

[0008] In view of the foregoing, there is a continuing need to develop new compounds that may be useful in the treatment of psychiatric or central nervous system disorders.

[0009] The reference to any prior art herein is not an admission or suggestion that this prior art forms part of the common general knowledge in any jurisdiction, or that this prior art would be understood by, considered relevant, and / or could reasonably be expected to be incorporated into other pieces of prior art by a person skilled in the art. Summary of the Invention

[0010] In one aspect, the present disclosure provides a compound of formula (I):

[0011] [ka] or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, During the ceremony, R 1 and R 2 But hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 together with the nitrogen atom to which they are attached, form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 But hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 alkylenecycloalkyl; Alternatively, R 3 , and R 1 and R 2 together with the atoms to which they are bonded to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 But hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C 1~4 selected from alkylene, C2-C4 alkenylene, and C2-C4 alkynylene; X 1 But N, NR 6 , O, or S; X 2 But, CR 7 , N, O, or S; Z 1 But, CR 8 or N, Z 2 But, CR 9 or N, Z 3 But, CR 10 or N, Z 4 But, CR 11 or N, R 6 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkylene P(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 and SO2R 12 , C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 12 , C(O)N(R 12 )2, OR 12 , N(R 12)2, NO2, SR 12 , and SO2R 12 each optionally substituted with one or more substituents independently selected from The C in question 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 12 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 12 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 , R 8 , R 9 , R 10 , and R 11 But 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R13 , 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, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is selected from 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or X 2 is CR 7 If R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8Heterocyclylalkyl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; Or X 1 NR 6 and X 2 is CR 7 If R 6 and R 7 These are combined with the atoms to which they are bonded to form C 4~10 Heterocycloalkyl or C 5~10 forming a heteroaryl, The C in question 4~10 Heterocycloalkyl and C 5~10 Heteroaryl is 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, C2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2 is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z 4 is CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 These are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 But hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X 2 , Z 1 , Z 2 , Z 3 , and Z4 is a heteroatom; The compound of formula (I) is

[0012] [ka] or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein:

[0013] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0014] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0015] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0016] [ka] Form one of the following:

[0017] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0018] In any one of the embodiments disclosed herein, R 3 is hydrogen.

[0019] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0020] In some embodiments, R 7 , R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0021] In some embodiments, R 7 , R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0022] In some embodiments, R 7 , R 8 , R 9 , R 10 , and R 11 When present, one or two of the groups are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0023] In some embodiments, R 7 H and C (if present) 1~6 alkyl, preferably R 7 (if present) is H.

[0024] In some embodiments, R 8 and R 9When present, they combine with the atoms to which they are attached to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0025] In some embodiments, R 8 and R 9 are combined to:

[0026] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0027] In some embodiments, R 8 and R 9 are combined to:

[0028] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0029] In some embodiments, L is C 1~4 It is alkylene.

[0030] In some embodiments, L is methylene.

[0031] In any one of the embodiments disclosed herein, R 6 is hydrogen and C 1~6 alkyl.

[0032] In any one of the embodiments disclosed herein, R 6 is hydrogen.

[0033] In some embodiments, X 1 is NH or N.

[0034] In some embodiments, the compound of formula (I) has formula (II):

[0035] [ka] wherein R 1 , R 2 , R 3 , R 7 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs, Z 1 , Z 2 , Z 3 , and Z 4 One or more of is N.

[0036] In some embodiments, the compound of Formula (I) has the formula (IIa):

[0037] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0038] In some embodiments, the compound of Formula (II) has the formula (IIb):

[0039] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0040] In some embodiments, the compound of Formula (I) has the formula (IIc):

[0041] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 9 , and R 11 is defined in one of the preceding paragraphs.

[0042] In some embodiments, the compound of Formula (I) has the formula (IId):

[0043] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 9 , and R 10 is defined in one of the preceding paragraphs.

[0044] In some embodiments, the compound of Formula (I) has Formula (III):

[0045] [ka] wherein R 1 , R 2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0046] In some embodiments, the compound of Formula (I) has the formula (IIIa):

[0047] [ka] wherein R 1 , R2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0048] In some embodiments, the compound of formula (I) has formula (IV):

[0049] [ka] wherein X2 is O or S, and R 1 , R 2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0050] In some embodiments, the compound of Formula (I) has the formula (IVa):

[0051] [ka] wherein R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0052] In any one of the embodiments disclosed herein, X 1 is O.

[0053] In some embodiments, the compound of formula (I) has formula (V):

[0054] [ka] wherein R 1 , R2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0055] In some embodiments, the compound of Formula (I) has the formula (Va):

[0056] [ka] wherein R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0057] In some embodiments, the compound of formula (I) is:

[0058] [ka] or any one of a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0059] In another aspect, the 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.

[0060] In another aspect, the present 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.

[0061] In another aspect, the present 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, an additional therapeutic agent, and a pharmaceutically acceptable excipient.

[0062] In another aspect, the present disclosure provides a method of treating a disease, disorder, or condition through activation of a serotonin receptor, the method comprising administering to a subject in need thereof a compound of formula (I):

[0063] [ka] or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, During the ceremony, R 1 and R 2 But hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, SR 4 , and SO2R 4 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C4-C 14 Alkylene heterocycloalkyl, C3-C8 heterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 But hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 alkylenecycloalkyl; Alternatively, R 3 , and R 1 and R 2 When one of these atoms combines with the atom to which it is attached, it forms C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is 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 , SO2R4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 But hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl and C 3~7 Heterocycloalkyl is 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C 1~4 selected from alkylene, C2-C4 alkenylene, and C2-C4 alkynylene; X 1 But N, NR 6 , O, or S; X 2 But, CR 7 , N, O, or S; Z 1 But, CR 8 or N, Z 2 But, CR 9 or N, Z 3 But, CR 10 or N, Z 4 But, CR 11 or N, R 6 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkylene P(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 and SO2R 12 , C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 12 , C(O)N(R 12 )2, OR 12 , N(R 12 )2, NO2, SR 12 , and SO2R 12 each optionally substituted with one or more substituents independently selected from The C in question 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 12 C containing one or two ring hetero moieties selected from3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 12 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, C 2~6 Haloalkynyl, C 3~6C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 , R 8 , R 9 , R 10 , and R 11 But 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is selected from 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 , NO2, N(R 13 )2, SR 13 , and SO2R 13 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or X 2 is CR 7 If R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6and optionally further substituted with one or more substituents selected from heterocycloalkyl; Or X 1 NR 6 and X 2 is CR 7 If R 6 and R 7 These are combined with the atoms to which they are bonded to form C 4~10 Heterocycloalkyl or C 5~10 forming a heteroaryl, The C in question 4~10 Heterocycloalkyl and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2 is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z 4 is CR 11 If R 8 and R9 , or R 9 and R 10 , or R 10 and R 11 These are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 But hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X 2 , Z 1 , Z 2 , Z 3 , and Z 4 is a heteroatom.

[0064] In some embodiments of this method, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0065] In some embodiments of this method, R 1and R 2 is C 1~4 alkyl.

[0066] In some embodiments of this method, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0067] [ka] Form one of the following:

[0068] In some embodiments of this method, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0069] In some embodiments of this method, R 3is hydrogen.

[0070] In some embodiments of this method, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~12 Heterocycloalkyl is a group that includes 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, SR 4 , NO2, SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0071] In some embodiments of this method, R 7 , R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0072] In some embodiments of this method, R 7 , R 8 R 9, R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0073] In some embodiments of this method, R 7 , R 8 R 9 , R 10 , and R 11 When present, one or two of the groups are halogen, C 1~6 Alkyl, C 1~6Haloalkyl and OR 13 R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 , R 9 , R 10 , and R 11 and the other of R is hydrogen. 8 and R 9 When present, they combine with the atoms to which they are attached to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0074] In some embodiments of this method, R 8 and R 9 are combined to:

[0075] [ka] C selected from 5~8Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0076] In some embodiments of this method, R 8 and R 9 are combined to:

[0077] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0078] In some embodiments of this method, L is C 1~4 It is alkylene.

[0079] In some embodiments of this method, L is methylene.

[0080] In some embodiments of this method, R 6 is hydrogen and C 1~6 alkyl.

[0081] In some embodiments of this method, R 6 is hydrogen.

[0082] In some embodiments of this method, X 1 is NH or N.

[0083] In some embodiments of this method, the compound of formula (I) is a compound of formula (II):

[0084] [ka] wherein R 1 , R 2 , R 3 ,,R 7 ,,Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs, Z 1 , Z 2 , Z 3 , and Z 4 One or more of is N.

[0085] In some embodiments of this method, the compound of formula (I) has formula (IIa):

[0086] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0087] In some embodiments of this method, the compound of formula (I) has formula (IIb):

[0088] [ka] wherein R 1 , R 2 , R 3 , R 7, R 8 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0089] In some embodiments of this method, the compound of Formula (I) has the formula (IIc):

[0090] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 9 , and R 11 is defined in one of the preceding paragraphs.

[0091] In some embodiments of this method, the compound of formula (I) has formula (IId):

[0092] [ka] wherein R 1 , R 2 , R 3 , R 7 , R 8 , R 9 , and R 10 is defined in one of the preceding paragraphs.

[0093] In some embodiments of this method, the compound of formula (I) is of formula (III):

[0094] [ka] wherein R 1 , R 2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0095] In some embodiments of this method, the compound of Formula (I) has the formula (IIIa):

[0096] [ka] wherein R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0097] In some embodiments of this method, the compound of formula (I) is of formula (IV):

[0098] [ka] wherein X2 is O or S, and R 1 , R 2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0099] In some embodiments of this method, the compound of formula (I) has formula (IVa):

[0100] [ka] wherein R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0101] In some embodiments of this method, the compound of formula (I) contains X as O. 1 It has.

[0102] In some embodiments of this method, the compound of formula (I) has formula (V):

[0103] [ka] wherein R 1 , R 2 , R 3 , Z 1 , Z 2 , Z 3 , and Z 4 is defined in one of the preceding paragraphs.

[0104] In some embodiments of this method, the compound of formula (I) has formula (Va):

[0105] [ka] wherein R 1 , R 2 , R 3 , R 8 , R 9 , R 10 , and R 11 is defined in one of the preceding paragraphs.

[0106] In some embodiments of this method, the compound of formula (I) is:

[0107] [ka] or any one of a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0108] In another aspect, the present disclosure provides a method of treating a disease, disorder, or condition through activation of a serotonin receptor, the method comprising administering to a subject in need thereof a compound of Formula (I), as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, in combination with another known agent useful in treating a disease, disorder, or condition through activation of a serotonin receptor.

[0109] In another aspect, the present disclosure provides a method of treating psychosis, the method comprising administering to a subject in need thereof a compound of formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, as defined in any one of the embodiments disclosed herein.

[0110] In some embodiments, the mental illness is selected from anxiety disorders; depression; mood disorders; psychotic disorders; impulse control and addiction disorders; substance addiction; obsessive-compulsive disorder (OCD); post-traumatic stress disorder (PTSD); stress response syndromes; dissociative disorders; depersonalization disorder; factitious disorder; sexual and gender disorders; somatic symptom disorders; hallucinations; delusions; psychotic disorders; and combinations thereof.

[0111] In another aspect, the present disclosure provides a method for treating a disease, disorder, or condition of the central nervous system (CNS) and / or a disease, disorder, or condition of the nervous system, the method comprising administering to a subject in need thereof a compound of formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, as defined in any one of the embodiments disclosed herein.

[0112] In some embodiments, the CNS disease, disorder or condition and / or nervous system disease, disorder or condition is a neurodegenerative disease such as neurodevelopmental diseases and Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia, cognitive disorders, Parkinson's disease, and Parkinson's disease-related diseases, such as Parkinsonism, corticobasal degeneration, and supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; fragile X syndrome; Angelman syndrome; hereditary ataxias. neuro-otological and oculomotor disorders; neurodegenerative diseases of retinal amyotrophic lateral sclerosis; tardive dyskinesia; hyperactivity disorder; attention deficit hyperactivity disorder and attention deficit disorder; restless legs syndrome; Tourette's syndrome; schizophrenia; autism spectrum disorder; tuberous sclerosis; Rett syndrome; cerebral palsy; disorders of the reward system including eating disorders such as anorexia nervosa and bulimia nervosa; binge eating disorder, trichotillomania, excoriation disorder, nail biting; migraine; fibromyalgia; and diseases of the nervous system including peripheral neuropathy of any etiology, and combinations thereof.

[0113] In another aspect, the disclosure provides a method for increasing neuroplasticity and / or increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound of Formula (I), as defined in any one of the embodiments disclosed herein, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, in an amount sufficient to increase neuroplasticity and / or increase dendritic spine density of the neuronal cell.

[0114] In another aspect, the present disclosure provides a method for treating body weight, comprising administering an effective amount of a compound of the present invention to a subject in need thereof.The treatment of body weight can include the treatment of weight gain; weight loss; metabolic disorders; weight gain associated with pharmaceutical intervention; weight gain associated with psychiatric illness (including those described herein); eating disorders such as anorexia nervosa, bulimia, cachexia; eating behavior; obesity; diabetes; insulin resistance; prediabetes; glucose intolerance; hyperlipidemia; and cardiovascular disease.

[0115] In another aspect, the present disclosure provides a method for activating serotonin receptors in cells, either in a biological sample or in a patient, comprising administering to the cells a compound of formula (I) as defined in any one of the embodiments disclosed herein.

[0116] Any embodiment in this specification should be applied mutatis mutandis to other embodiments unless otherwise specified.

[0117] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended as examples only. Functionally equivalent products, compositions, and methods are clearly within the scope of the invention as described herein.

[0118] Further aspects of the invention and further embodiments of the aspects described in the preceding paragraphs will become apparent from the following description, given by way of example and with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0119] [Figure 1] Plasma concentrations of a subset of exemplary compounds P-8, P-5, P-3, and P-1 in male C57BL / 6 mice after IP administration at 10 mg / kg as described in Example 49. [Figure 2] Time binning and mean ± SD (n=3) HTR counts for a subset of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 50. [Figure 3] Temperature results shown as mean ± SD (n=3) HTR counts for a subset of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 50. [Figure 4]Locomotor results (total distance traveled) shown as mean ± SD (n=3) HTR counts for a subset of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 50. [Figure 5] Locomotor activity results (distance / time) shown as mean ± SD (n=3) HTR counts for a subset of exemplary compounds P-4, P-3, and P-1 in male C57BL / 6 mice after SC administration across several doses, as described in Example 50. [Figure 6] Time immobilization results from the tail suspension test (TST) experiment described in Example 51 for compounds P-3.2HCl (3 mg / kg, 10 mg / kg) and P-8.2HCl (3 mg / kg, 10 mg / kg, 30 mg / kg) compared to ketamine (10 mg / kg) and vehicle. DETAILED DESCRIPTION OF THE INVENTION

[0120] The invention disclosed and defined herein will be understood to extend to all alternative combinations of two or more of the individual features mentioned or made apparent from the text or drawings, all of which different combinations constitute various alternative aspects of the invention. definition For purposes of interpreting this specification, terms used in the singular will also include the plural and vice versa.

[0121] 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.

[0122] The term "treatment" or "treating" a subject includes delaying, slowing, stabilizing, curing, curing, mitigating, alleviating, altering, repairing, making less severe, improving, ameliorating, or affecting a disease or condition, a sign or symptom of a disease or condition, or the risk of (or susceptibility to) a disease or condition. The term "treating" refers to any indication of success in treating or improving an injury, condition, or condition, including any objective or subjective parameter such as decline; remission; slowing the rate of deterioration; reducing the severity of the disease; stabilization; reducing signs or symptoms or making the injury more tolerable to the individual; slowing the rate of degeneration or decline; or making the end point of degeneration less debilitating.

[0123] In particularly preferred embodiments, the methods of the invention may prevent or reduce the severity of, or inhibit or minimize the progression of, the signs or symptoms of the diseases or conditions described herein, and thus have therapeutic and prophylactic utility.

[0124] As used herein, "preventing" or "prevention" is intended to refer at least to a reduction in the likelihood of the risk (or susceptibility) of acquiring a disease or disorder (i.e., preventing at least one clinical sign or symptom of the disease from developing in an individual who may be exposed to or susceptible to the disease, but who has not yet experienced or displayed a sign or symptom of the disease). Biological and physiological parameters for identifying such patients are provided herein and are well known to physicians.

[0125] As used herein, the terms "subject" and "patient" can be used interchangeably. The terms "individual" and "patient," respectively, refer to animals treatable by the compounds and / or methods, including, but not limited to, for example, dogs, cats, horses, sheep, pigs, cows, etc., as well as humans and non-human primates. Unless otherwise specified, "subject" or "patient" can include both male and female genders. Furthermore, this also includes subjects or patients, preferably humans, suitable for receiving treatment with the pharmaceutical compositions and / or methods of the present invention.

[0126] The term "selective" refers to greater activity for a first target (e.g., a 5HT receptor subtype) compared to a second target (e.g., a second 5HT receptor subtype). In some embodiments, a compound has at least 1.25-fold, at least 1.5-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 10-fold, or at least 100-fold greater selectivity for a first target compared to a second target. In some embodiments, the compounds described herein have a 5-HT 2B and / or 5-HT 2C , preferably 5-HT 2B 5-HT receptor subtypes compared to one or more other 5-HT receptor subtypes, such as 2A In some embodiments, the compounds described herein are selective for the 5-HT receptor. 2A and / or 5-HT 2B , preferably 5-HT 2B 5-HT receptor subtypes compared to one or more other 5-HT receptor subtypes, such as 2C It is selective for the receptor.

[0127] As used herein when referring to a measurable value, such as an amount, duration over time, etc., "about" is meant to encompass variations of ±20% or ±10%, in some instances ±5%, in some instances ±1%, and in some instances ±0.1% from the specified value, where such variations are appropriate for practicing the disclosed methods.

[0128] Ranges: Throughout this disclosure, various aspects of the invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within that range. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within that range, e.g., 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.

[0129] As used herein, the term "alkyl" refers to a straight or branched chain hydrocarbon radical having 1 to 12 carbon atoms, or any range therebetween, i.e., it contains 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, t-butyl, n-pentyl, isopentyl, and the like.

[0130] As used herein, the terms "C1-C2 alkyl," "C1-C3 alkyl," and "C1-C6 alkyl" refer to an alkyl group, as defined herein, each containing at least 1 and at most 2, 3, or 6 carbon atoms, or any range therebetween (e.g., an alkyl group containing 2 to 5 carbon atoms is also within the C1-C6 range).

[0131] The term "alkylene" refers to a straight-chain or branched saturated aliphatic radical having the number of carbon atoms indicated and linking at least two other groups, i.e., divalent hydrocarbon radicals. The two moieties linked to the alkylene can be attached to the same atom or different atoms of the alkylene group. For example, a straight-chain alkylene is -(CH2) n- 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.

[0132] The term "alkenyl," whether used alone or as part of another group, refers to a straight-chain or branched saturated alkylene group, i.e., a saturated carbon chain containing substituents at two of its termini. The number of possible carbon atoms in the referenced alkylene group is indicated by the prefix "C n1~n2 For example, C 2~6 The term alkylene refers to an alkylene group having 2, 3, 4, 5, or 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl.

[0133] As used herein, the term "alkynyl," whether used alone or as part of another group, means a straight or branched chain unsaturated alkynyl group containing at least one triple bond. The number of carbon atoms possible in the referenced alkyl group is indicated by the prefix "C n1~n2 For example, C 2~6The term alkynyl refers to an alkynyl group having 2, 3, 4, 5, or 6 carbon atoms. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butadinyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl.

[0134] The term "cycloalkyl" is intended to include monocyclic, bicyclic, or tricyclic alkyl groups. The number of possible carbon atoms in the referenced cycloalkyl group is determined by the prefix "C n1~n2 For example, C 3~8 The term cycloalkyl refers to a cycloalkyl group having 3, 4, 5, 6, 7, or 8 carbon atoms. In some embodiments, the cycloalkyl group has 3 to 12, 3 to 10, 3 to 8, 3 to 6, or 3 to 5 carbon atoms in the ring. In some embodiments, the cycloalkyl group has 5 or 6 ring carbon atoms. Examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, the cycloalkyl group has 3 to 8, 3 to 7, 3 to 6, 4 to 6, 3 to 5, or 4 to 5 ring carbon atoms. Bicyclic and tricyclic ring systems include bridged, spiro, and fused cycloalkyl ring systems. Examples of bicyclic and tricyclic cycloalkyl systems include, but are not limited to, bicyclo[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, adamantyl, and decalinyl.

[0135] The term "alkylenecycloalkyl" refers to a radical having an alkyl component and a cycloalkyl component, where the alkyl component connects the cycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least a divalent alkylene and connects the cycloalkyl component to the point of attachment. In some cases, the alkyl component may be absent. The alkyl component may be any of C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 The cycloalkyl moiety is as defined herein. x~y Alkylenecycloalkyl 」 The numerical range of x to y relates to the total number of alkyl carbons and cycloalkyl ring atoms. Exemplary alkylenecycloalkyl groups include, but are not limited to, methylenecyclopropyl, methylenecyclobutyl, methylenecyclopentyl, and methylenecyclohexyl.

[0136] 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 possible carbon atoms in the referenced aryl group can be determined by the prefix "C n1~n2 For example, C 6~12The term aryl refers to an aryl group having 6, 7, 8, 9, 10, 11, or 12 carbon atoms. The aryl group can contain any suitable number of ring atoms, for example, 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.

[0137] The term "alkylenearyl" refers to a radical having an alkyl and aryl moiety, where the alkyl moiety connects the aryl moiety to the point of attachment. The alkyl moiety is as defined above, except that the alkyl moiety is at least divalent alkylene and connects the aryl moiety to the point of attachment. The alkyl moiety is selected from the group consisting of C 1~6 , C 1~2 , C 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. x~yThe numerical range of x to y in "alkylenearyl" relates to the total number of alkyl carbon and aryl ring atoms. Examples of alkylenearyl groups include, but are not limited to, benzyl and ethylenephenyl.

[0138] As used herein, the term "alkoxy" refers to an alkyl group, as defined herein, covalently attached via an O linkage. Alkoxy groups are optionally substituted with substituents. Examples of "alkoxy" as used herein include, but are not limited to, methoxy, ethoxy, propoxy, isoproxy, butoxy, isobutoxy, tert-butoxy, and pentoxy.

[0139] As used herein, the terms "C1-C2 alkoxy," "C1-C3 alkoxy," and "C1-C6 alkoxy" refer to an alkoxy group, as defined herein, each containing at least 1 and at most 2, 3, or 6 carbon atoms, or any range therebetween (e.g., an alkoxy group containing 2 to 5 carbon atoms is also within the C1-C6 range).

[0140] As used herein, the term "alkylamine" refers to an alkyl group, as defined herein, bearing one or more amino groups. The amino groups can be primary, secondary, or tertiary. The alkylamine can be further substituted with a hydroxy 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 link the alkylamine to the point of attachment to the rest of the compound, be in the omega position of the alkyl group, or link at least two carbon atoms of the alkyl group together.

[0141] As used herein, the terms "C1-C2 alkylamine," "C1-C3 alkylamine," and "C1-C6 alkylamine" refer to an alkylamine group, as defined herein, each containing at least 1 and at most 2, 3, or 6 carbon atoms, or any range therebetween (e.g., an alkylamine group containing 2 to 5 carbon atoms is also within the C1-C6 range).

[0142] As used herein, the term "alkylsulfonyl" refers to an alkyl group, as defined herein, bearing one or more sulfonyl groups. The sulfonyl group may be linked to the alkylsulfonyl at its point of attachment to the remainder of the compound, may be at the omega position of the alkyl group, or may link at least two carbon atoms of the alkyl group together.

[0143] As used herein, the terms "C1-C2 alkylsulfonyl," "C1-C3 alkylsulfonyl," and "C1-C6 alkylsulfonyl" refer to alkylsulfonyl groups, as defined herein, each containing at least 1, and up to 2, 3, or 6 carbon atoms, or any range therebetween (e.g., an alkylsulfonyl group containing 2 to 5 carbon atoms is also within the C1-C6 range).

[0144] As used herein, the term "heteroatom" means an atom of any element other than carbon or hydrogen. Examples of heteroatoms include nitrogen, oxygen, sulfur, and phosphorus. Preferred heteroatoms include N, O, and S, preferably N and O.

[0145] As used herein, the term "hetero moiety" refers to a chemical group that includes a heteroatom. Examples of hetero moieties include O, S, S(O), SO, N, and NH.

[0146] As used herein, "substituent" refers to a molecular moiety that is covalently bonded to an atom in the molecule of interest. For example, a "ring substituent" may be a moiety such as a halogen, an alkyl group, or other substituents described herein that are covalently bonded to a ring member atom, preferably a carbon atom or a nitrogen atom. As used herein, the term "substituted" means that any one or more hydrogens on the designated atom are replaced with a selection from the designated substituents, provided that the replacement does not exceed the normal valence of the designated atom, and that the replacement results in a stable compound, i.e., a compound that can be isolated, characterized, and tested for biological activity.

[0147] Terms such as "optionally substituted" or "can be substituted," as used throughout this specification, indicate that a group may or may not be further substituted or fused (so as to form a polycyclic ring system) with one or more non-hydrogen substituents. Suitable chemically feasible substituents for a particular functional group will be apparent to one of ordinary skill in the art.

[0148] Examples of the substituent include, but are not limited to, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C3-C7 heterocyclyl, C3-C7 cycloalkyl, C1-C6 alkoxy, C1-C6 alkylsulfanyl, C1-C6 alkylsulfenyl, C1-C6 alkylsulfonylamino, arylsulfonoamino, alkylcarboxy, alkylcarboxyamido, oxo, hydroxy, mercapto, amino, acyl, carboxy, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aroyl, aroylamino, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, nitro, cyano, halo, ureido, and C1-C6 perfluoroalkyl. Preferably, the substituent includes amino, halo, C1-C6 alkyl, amido, or hydroxyl.

[0149] As used herein, the term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I), and the term "halo" refers to the halogen radicals fluoro (-F), chloro (-Cl), bromo (-Br), and iodine (-I). Preferably, "halo" is fluoro or chloro.

[0150] As used herein, the term "haloalkyl" refers to an alkyl group, as defined herein, in which one or more (up to all) available hydrogen atoms are replaced with halogen. In some cases, the term "perfluoro" can be used to define a compound or radical in which all hydrogen atoms are replaced with fluorine. For example, perfluoromethyl refers to 1,1,1-trifluoromethyl.

[0151] As used herein, the terms "C1-C2 haloalkyl," "C1-C3 haloalkyl," and "C1-C6 haloalkyl" refer to a haloalkyl group, as defined herein, each containing at least 1, and up to 2, 3, or 6 carbon atoms, or any range therebetween (e.g., a haloalkyl group containing 2 to 5 carbon atoms is also within the C1-C6 range).

[0152] For example, but not limited to, a C1 haloalkyl group can be fluoromethyl, or difluoromethyl, or trifluoromethyl.

[0153] As used herein, the term "haloalkenyl" refers to an alkenyl group as defined above in which one or more available hydrogen atoms has been replaced with a halogen. Thus, for example, "C 1~6 "Haloalkenyl" (or "C1-C6 haloalkenyl") refers to a C1-C6 linear or branched alkenyl group as defined above having one or more halogen substituents.

[0154] As used herein, the term "haloalkynyl" refers to an alkynyl group as defined above in which one or more available hydrogen atoms has been replaced with a halogen. Thus, for example, "C 1~6 "Haloalkynyl" (or "C1-C6 haloalkynyl") refers to a C1-C6 linear or branched alkynyl group as defined above having one or more halogen substituents.

[0155] As used herein, the term haloalkoxy refers to an alkoxy group, as defined herein, substituted with at least one halogen.

[0156] The term "amino" or "amine" refers to the group --NH.sub.2.

[0157] The term "substituted amino" or "secondary amino" refers to an amino group in which a hydrogen has been replaced, for example, by a C1-C6 alkyl group ("C1-C6 alkylamino"), an aryl or aralkyl group ("arylamino", "aralkylamino"), etc. Preferred are C1-C3 alkylamino groups such as methylamino (NHMe), ethylamino (NHEt), and propylamino (NHPr).

[0158] The term "disubstituted amino" or "tertiary amino" refers to an amino group in which two hydrogens have been replaced, for example, by a C1-C6 alkyl group ("dialkylamino"), an aryl and alkyl group ("aryl(alkyl)amino"), which may be the same or different. Di(C1-C3 alkyl)amino groups are preferred, for example, dimethylamino (NMe2), diethylamino (NEt2), dipropylamino (NPr2), and variations thereof (e.g., N(Me)(Et)).

[0159] The term "nitro" refers to the group -NO2.

[0160] The terms "cyano" and "nitrile" refer to the group --CN.

[0161] The terms "amido" or "amide" refer to the group -C(O)NH2.

[0162] The term "substituted amido" or "substituted amide" refers to an amide group in which a hydrogen has been replaced with, for example, a C1-C6 alkyl group ("C1-C6 alkylamido" or "C1-C6 alkylamido"), an aryl ("arylamido"), an aralkyl group ("aralkylamido"), etc. For example, C1-C3 alkylamido groups such as methylamido (-C(O)NHMe), ethylamido (-C(O)NHEt), and propylamido (-C(O)NHPr) are preferred, including their reverse amides (e.g., NHMeC(O)-, -NHEtC(O)-, and -NHPrC(O)-).

[0163] The term "disubstituted amido" or "disubstituted amide" refers to an amide group in which two hydrogens have been replaced, for example, by a C1-C6 alkyl group ("di(C1-C6 alkyl)amide" or "di(C1-C6 alkyl)amide"), an aralkyl and alkyl group ("alkyl(aralkyl)amide"). For example, di(C1-C3 alkyl)amide groups such as dimethylamide (-C(O)NMe2), diethylamide (-C(O)NEt2), and dipropylamide (-C(O)NPr2), as well as variations thereof (e.g., C(O)N(Me)Et, etc.), are preferred, including reverse amides thereof.

[0164] The term "sulfonyl" refers to the group -SO2H.

[0165] The term "substituted sulfonyl" refers to a sulfonyl group in which the hydrogen has been replaced with, for example, a C1-C6 alkyl group ("sulfonyl C1-C6 alkyl"), aryl ("arylsulfonyl"), aralkyl ("aralkylsulfonyl"), etc. Preferred are sulfonyl C1-C3 alkyl groups such as, for example, -SO2Me, -SO2Et, and -SO2Pr.

[0166] The term "sulfonylamido" or "sulfonamide" refers to the group -SO2NH2.

[0167] The terms "substituted sulfonamide" or "substituted sulfonamide" refer to sulfonylamide groups in which the hydrogen has been replaced, for example, with a C1-C6 alkyl group ("sulfonylamide C1-C6 alkyl"), aryl ("arylsulfonamide"), aralkyl ("aralkylsulfonamide"), etc. Sulfonylamide C1-C3 alkyl groups, such as SO2NHMe, SO2NHEt, and SO2NHPr, are preferred, including their reverse sulfonamides (e.g., -NHSO2Me, NHSO2Et, and -NHSO2Pr).

[0168] The terms "disubstituted sulfonamido" or "disubstituted sulphonamide" refer to a sulfonyl amide group in which two hydrogens have been replaced, for example, by C1-C6 alkyl groups ("sulfonyl amide di(C1-C6 alkyl)"), aralkyl, and alkyl groups ("sulfonamido(aralkyl)alkyl"), which may be the same or different. For example, sulfonyl amide di(C1-C3 alkyl) groups such as -SONMe, -SONEt, and -SONPr, and variations thereof (e.g., SON(Me)Et, etc.), are preferred, including their reverse sulfonamides (e.g., -N(Me)SOMe, etc.).

[0169] The term "sulfate" refers to the group OS(O)OH and includes groups in which the hydrogen has been replaced, for example, by a C-C alkyl group ("alkyl sulfate"), aryl ("aryl sulfate"), aralkyl ("aralkyl sulfate"), etc. Preferred are C-C alkyl sulfates such as, for example, OS(O)OMe, OS(O)OEt, and OS(O)OPr.

[0170] The term "sulfonate" refers to the group SO3H and includes groups in which the hydrogen has been replaced, for example, by a C1-C6 alkyl group ("alkylsulfonate"), aryl ("arylsulfonate"), aralkyl ("aralkylsulfonate"), etc. 1~ C3 alkyl sulfonates are preferred.

[0171] The term "amino acid" as defined herein refers to a moiety containing an amino group and a carboxyl group linked by at least one carbon. The amino acid may refer to a natural or unnatural amino acid, preferably a natural amino acid such as alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine; preferably, the amino acid is arginine, lysine, or histidine, most preferably lysine.

[0172] The term "carboxylate" or "carboxyl" refers to the group --COO-- or --COOH.

[0173] The term "carbamate" or "carbomyl" refers to the group -OC(O)NH. Carbamates can be substituted or disubstituted, for example with alkyl groups such as, but not limited to, C1-C6 alkyl.

[0174] The term "carbonate" refers to the group -OC(O)O- or -OC(O)OH.

[0175] The term "alkyl carbonate," as defined herein, refers to a carbonate group in which a hydrogen has been replaced, for example, by a C1-C6 alkyl group, an aryl or aralkyl group ("aryl carbonate" or "aralkyl carbonate"). Preferred are CO3C1-C3 alkyl groups, such as methyl carbonate (CO3Me), ethyl carbonate (CO3Et), and propyl carbonate (CO3Pr).

[0176] The term "ester" refers to an ester in which the hydrogen is present in an ester, e.g., C 1~ It refers to a carboxyl group substituted with a C alkyl group ("carboxyl C-C alkyl" or "alkyl ester"), an aryl or aralkyl group ("aryl ester" or "aralkyl ester"), or the like. For example, CO2C1-C3 alkyl groups such as methyl ester (CO2Me), ethyl ester (CO2Et), and propyl ester (CO2Pr) are preferred, including their reverse esters (e.g., -OC(O)Me, -OC(O)Et, and -OC(O)Pr).

[0177] The term "heterocyclyl" (unless otherwise specified) refers to a moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compound having 3 to 12 ring atoms (1, 2, 3, 4 or more of which are ring heteroatoms independently selected from, e.g., O, S, and N, or ring heteromoieties independently selected from, e.g., O, S, S(O), SO, N, and NH). A heterocyclyl group may be denoted by the prefix C. n1~n2 or "n1-n2", this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, where one or more, preferably 1, 2, 3, 4 or more, of the ring atoms are replaced with a heteroatom or heteromoiety.

[0178] In this context, the prefixes 3-, 4-, 5-, 6-, 7-, 8-, 9-, and 10- denote the number of ring atoms, or range of ring atoms, whether carbon atoms or heteroatoms. For example, as used herein, "C 3~10The term "heterocyclyl" or "3- to 10-membered heterocyclyl" refers to a heterocyclyl group having 3, 4, 5, 6, 7, 8, 9, or 10 ring atoms. Examples of heterocyclyl groups include 5- to 6-membered monocyclic heterocyclyl and 9- to 10-membered fused bicyclic heterocyclyl.

[0179] Examples of monocyclic heterocyclyl groups include those containing one nitrogen atom, such as aziridine (3-membered ring), azetidine (4-membered ring), pyrrolidine (tetrahydropyrrole), pyrroline (e.g., 3-pyrroline, 2,5-dihydropyrrole), 2H-pyrrole or 3H-pyrrole (isopyrrole, isoazole) or pyrrolidinone (5-membered ring), piperidine, dihydropyridine, tetrahydropyridine (6-membered ring), and azepine (7-membered ring); imidazoline, pyrazolidine (diazolidine), imidazoline, pyrazoline, pyrazolidine ... Those containing two nitrogen atoms, such as phosphorus (dihydropyrazole) (5-membered ring) and piperazine (6-membered ring); those containing one oxygen atom, such as oxirane (3-membered ring), oxetane (4-membered ring), oxolane (tetrahydrofuran), oxole (dihydrofuran) (5-membered ring), oxane (tetrahydropyran), dihydropyran, pyran (6-membered ring), and oxepin (7-membered ring); those containing two oxygen atoms, such as dioxolane (5-membered ring), dioxane (6-membered ring), and dioxepane (7-membered ring); trioxane Those containing three oxygen atoms, such as thiirane (6-membered ring); those containing one sulfur, such as thiirane (3-membered ring), thietane (4-membered ring), thiolane (tetrahydrothiophene) (5-membered ring), thiane (tetrahydrothiopyran) (6-membered ring), and thiepane (7-membered ring); those containing one nitrogen and one oxygen, such as tetrahydrooxazole, dihydrooxazole, tetrahydroisoxazole, dihydroisoxazole (5-membered ring), morpholine, tetrahydrooxazine, dihydrooxazine, and oxazine (6-membered ring). those containing one nitrogen and one sulfur atom, such as thiazoline, thiazolidine (5-membered ring), and thiomorpholine (6-membered ring); those containing two nitrogen and one oxygen atom, such as oxadiazine (6-membered ring); those containing one oxygen and one sulfur atom, such as oxathiol (5-membered ring) and oxathiane (thioxane) (6-membered ring); and those containing one nitrogen, one oxygen, and one sulfur atom, such as oxathiazine (6-membered ring).

[0180] Heterocyclyl also encompasses heteroaryl (aromatic heterocyclyl) and heterocycloalkyl (non-aromatic heterocyclyl). Such groups may be substituted or unsubstituted.

[0181] The term "aromatic heterocyclyl" can be used interchangeably with the term "heteroaromatic" or the terms "heteroaryl" or "hetaryl." The heteroatoms in an aromatic heterocyclyl group can be independently selected from N, S, and O. An aromatic heterocyclyl group can contain 1, 2, 3, 4, or more ring heteroatoms. A heteroaryl group can be denoted by the prefix C n1~n2 or "n1-n2", this prefix indicates the number of carbon atoms in the corresponding aryl group, where one or more, preferably 1, 2, 3, 4 or more, of the ring atoms are replaced with a heteroatom. In the case of fused aromatic heterocyclyl groups, only one of the rings may contain a heteroatom, and all rings need not be aromatic.

[0182] As used herein, "heteroaryl" is used to refer to a heterocycle having aromatic character and includes aromatic monocyclic ring systems and polycyclic (e.g., bicyclic) ring systems containing one or more aromatic rings. The term aromatic heterocyclyl also includes pseudoaromatic heterocyclyl. The term "pseudoaromatic" refers to a ring system that is not strictly aromatic but is stabilized by electron delocalization and behaves in a manner similar to an aromatic ring. Thus, the term aromatic heterocyclyl includes polycyclic ring systems in which all of the fused rings are aromatic, provided that at least one ring is aromatic, as well as ring systems in which one or more rings are non-aromatic. In polycyclic ring systems containing both aromatic and non-aromatic rings fused together, groups may be attached to another moiety by either the aromatic ring or the non-aromatic ring.

[0183] Examples of heteroaryl groups are monocyclic and bicyclic groups containing 5 to 10 ring members. Heteroaryl groups can be, for example, 5- or 6-membered monocyclic rings, or bicyclic structures formed from fused 5- and 6-membered rings, or two fused 6-membered rings, or two fused 5-membered rings. Each ring can contain up to about four heteroatoms, typically selected from nitrogen, sulfur, and oxygen. Heteroaryl rings contain up to four heteroatoms, more typically up to three heteroatoms, and more usually up to two heteroatoms, e.g., a single heteroatom. In one embodiment, a heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atoms in a heteroaryl ring can be basic, as in the case of imidazole or pyridine, or essentially non-basic, as in the case of indole or pyrrole nitrogens. Generally, the number of basic nitrogen atoms present in a heteroaryl group, including any amino group substituents on the ring, is less than five.

[0184] An aromatic heterocyclyl group can be a 5- or 6-membered monocyclic aromatic ring system.

[0185] Examples of 5-membered monocyclic heteroaryl groups include, but are not limited to, furanyl, thienyl, pyrrolyl, oxazolyl, oxadiazolyl (including 1,2,3 and 1,2,4 oxadiazolyl and furazanyl, i.e., 1,2,5-oxadiazolyl), thiazolyl, isoxazolyl, isothiazolyl, pyrazolyl, imidazolyl, triazolyl (including 1,2,3, 1,2,4 and 1,3,4 triazolyl), oxatriazolyl, tetrazolyl, thiadiazolyl (including 1,2,3 and 1,3,4 thiadiazolyl), and the like.

[0186] Examples of 6-membered monocyclic heteroaryl groups include, but are not limited to, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyranyl, oxazinyl, dioxinyl, thiazinyl, thiadiazinyl, etc. Examples of 6-membered aromatic heterocyclyls containing nitrogen include pyridyl (one nitrogen), pyrazinyl, pyrimidinyl, and pyridazinyl (two nitrogens).

[0187] The aromatic heterocyclyl group may also be a bicyclic or polycyclic heteroaromatic ring system, such as a fused ring system (including purine, pteridinyl, naphthyridinyl, 1H-thieno[2,3-c]pyrazolyl, thieno[2,3-b]furyl, etc.) or a linked ring system (oligothiophene, polypyrrole, etc.). Fused ring systems may also include 5- or 6-membered heterocyclyls fused to a carbocyclic aromatic ring such as phenyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, etc., e.g., a 5-membered aromatic heterocyclyl containing a nitrogen atom fused to a phenyl ring, a 5-membered aromatic heterocyclyl containing one or two nitrogen atoms fused to a phenyl ring.

[0188] Bicyclic heteroaryl groups include, for example, a) a benzene ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms, b) a pyridine ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms, c) a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms, d) a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2, or 3 ring heteroatoms, e) a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms, f) an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms, g) an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms. h) an isoxazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; i) a thiazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; j) an isothiazole ring fused to a 5- or 6-membered ring containing one or two ring heteroatoms; k) a thiophene ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; l) a furan ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; m) a cyclohexyl ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms; and n) a cyclopentyl ring fused to a 5- or 6-membered ring containing one, two, or three ring heteroatoms.

[0189] Particular examples of bicyclic heteroaryl groups containing a 5-membered ring fused to another 5-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).

[0190] Specific examples of bicyclic heteroaryl groups containing a 6-membered ring fused to a 5-membered ring include, but are not limited to, benzofuran, benzothiophene, benzimidazole, benzoxazole, isobenzoxazole, benzisoxazole, benzothiazole, benzisothiazole, isobenzofuran, indole, isoindole, indolizine, indoline, isoindoline, purine (e.g., adenine, guanine), indazole, pyrazolopyrimidine (e.g., pyrazolo[1,5-a]pyrimidine), benzodioxole, and pyrazolopyridine (e.g., pyrazolo[1,5-a]pyridine) groups. A further example of a 6-membered ring fused to a 5-membered ring is a pyrrolopyridine group, such as a pyrrolo[2,3-b]pyridine group.

[0191] Specific examples of bicyclic heteroaryl groups containing two fused six-membered rings include, but are not limited to, quinoline, isoquinoline, chroman, thiochroman, chromene, isochromene, isochroman, benzodioxane, quinolizine, benzoxazine, benzodiazine, pyridopyridine, quinoxaline, quinazoline, cinnoline, phthalazine, naphthyridine, and pteridine groups.

[0192] Examples of heteroaryl groups containing aromatic and non-aromatic rings include tetrahydronaphthalene, tetrahydroisoquinoline, tetrahydroquinoline, dihydrobenzothiophene, dihydrobenzofuran, 2,3-dihydro-benzo[1,4]dioxine, benzo[1,3]dioxole, 4,5,6,7-tetrahydrobenzofuran, indoiine, isoindoline, and indane groups.

[0193] Thus, examples of aromatic heterocycles fused to carbocyclic aromatic rings include, but are not limited to, benzothiophenyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzimidazolyl, indazolyl, benzoxazolyl, benzisoxazolyl, isobenzoxazolyl, benzothiazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzotriazinyl, phthalazinyl, carbolinyl, and the like.

[0194] The term "heterocycloalkyl" or "non-aromatic heterocyclyl" includes optionally substituted saturated and unsaturated rings containing at least one heteroatom, such as N, S, and O, or heteromoiety, such as O, S, S(O), SO, N, and NH. The ring may contain 1, 2, 3, 4, or more heteroatoms or heteromoieties. Heterocycloalkyl groups are denoted by the prefix C. n1~n2 or "n1-n2," the prefix indicates the number of carbon atoms in the corresponding carbocyclic group, with one or more, preferably one, two, three, four, or more, of the ring atoms being replaced with a heteroatom or heteromoiety. A ring can be a monocyclic ring or part of a polycyclic ring system. Polycyclic ring systems include fused rings and spiro rings. Not all rings in a non-aromatic heterocyclic polycyclic ring system must contain heteroatoms, provided that at least one ring contains one or more heteroatoms.

[0195] The non-aromatic heterocyclyl can be a 3- to 8-membered monocyclic ring.

[0196] Examples of 5-membered non-aromatic heterocyclyl rings include 2H-pyrrolyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrazolinyl, 2-pyrazolinyl, 3-pyrazolinyl, pyrazolidinyl, 2-pyrazolidinyl, 3-pyrazolidinyl, imidazolidinyl, 3-dioxalanyl, thiazolidinyl, isoxazolidinyl, 2-imidazolinyl, and the like.

[0197] Examples of 6-membered non-aromatic heterocyclyls include piperidinyl, piperidinonyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 2H-pyranyl, 4H-pyranyl, thianyl, thianyloxide, thianyldioxide, piperazinyl, diozanyl, 1,4-dioxinyl, 1,4-dithianyl, 1,3,5-triozalanyl, 1,3,5-trithianyl, 1,4-morpholinyl, thiomorpholinyl, 1,4-oxathianyl, triazinyl, 1,4-thiazinyl, and the like.

[0198] Examples of 7-membered non-aromatic heterocyclyls include azepanyl, oxepanyl, thiepanyl, and the like.

[0199] Non-aromatic heterocyclyl rings can also be bicyclic heterocyclyl rings, such as linked ring systems (e.g., uridinyl, etc.) or fused ring systems. Fused ring systems include non-aromatic 5-, 6-, or 7-membered heterocyclyls fused to a carbocyclic aromatic ring, such as phenyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, etc. Examples of non-aromatic 5-, 6-, or 7-membered heterocyclyls fused to a carbocyclic aromatic ring include indolinyl, benzodiazepinyl, benzazepinyl, dihydrobenzofuranyl, etc.

[0200] The term "alkyleneheteroaryl" refers to a radical having an alkyl component and a heteroaryl component, where the alkyl component connects the heteroaryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least a divalent alkylene and connects the heteroaryl component to the point of attachment. In some cases, the alkyl component may be absent. The alkyl component may be any of C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 The heteroaryl moiety is as defined herein. x~y Alkylenecycloalkyl 」 The numerical range of x to y relates to the total number of alkyl carbon and heteroaryl ring atoms (carbon and heteroatoms combined).

[0201] The term "alkyleneheterocycloalkyl" refers to a radical having an alkyl component and a heterocycloalkyl component, where the alkyl component connects the heterocycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least a divalent alkylene and connects the heterocycloalkyl component to the point of attachment. In some cases, the alkyl component may be absent. The alkyl component may be any of C 1~6 , C 1~2 , C 1~3 , C 1~4 , C 1~5 , C 2~3 , C 2~4 , C 2~5 , C 2~6 , C 3~4 , C 3~5 , C 3~6 , C 4~5 , C 4~6 , and C 5~6 Heterocycloalkyl moieties are as defined herein. x~y The numerical range of x to y for "alkyleneheterocycloalkyl" relates to the total number of alkyl carbons and heterocycloalkyl ring atoms (carbons and heteroatoms combined).

[0202] As used herein, the term solvate refers to a complex of a compound with a solvent, either stoichiometric or non-stoichiometric.Solvates are often formed during the crystallization process using pharmaceutically acceptable solvents such as water, ethanol, etc. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol.

[0203] As used herein, the term "polymorph" refers to different crystal packing arrangements of a compound with the same elemental composition. Polymorphs typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardnesses, crystal shapes, optical and electrical properties, stability, and solubility. Depending on various factors such as the recrystallization solvent, crystallization rate, and storage temperature, a single crystalline form may predominate.

[0204] As used herein, the term "metabolite" refers to a derivative of a compound that is formed when the compound is metabolized. The term "active metabolite" refers to a biologically active derivative of a compound that is formed when the compound is metabolized. As used herein, the term "metabolized" refers to the sum of processes by which a particular substance is transformed by an organism, including, but not limited to, hydrolysis reactions and reactions catalyzed by enzymes. Thus, enzymes may cause specific structural changes to the compound. Metabolites of the compounds disclosed herein are optionally identified by either 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.

[0205] The definitions and conventions of stereochemistry used herein generally follow those of S.P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York, and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994. The compounds of the present invention may contain asymmetric or chiral centers and, therefore, exist in different stereoisomeric forms. The term "stereoisomers" refers to compounds that have identical chemical constitution but differ with regard to the arrangement of atoms or groups in space. As used herein, the term "stereoisomers" includes, but is not limited to, diastereomers, enantiomers, and atropisomers, as well as mixtures thereof, such as racemic mixtures.

[0206] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reaction, etc., commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts of amino groups formed 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 using other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, nate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. compound The present disclosure provides a compound of formula (I):

[0207] [ka] or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, During the ceremony, R 1 and R 2 But hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, SR4 , and SO2R 4 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is 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 2~6Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 But hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C 4~14 alkylenecycloalkyl; Alternatively, R 3 , and R 1 and R 2 When one of these atoms combines with the atom to which it is attached, it forms C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 But hydrogen, C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 But hydrogen, C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C 1~4 selected from alkylene, C2-C4 alkenylene, and C2-C4 alkynylene; X 1 But N, NR 6 , O, or S; X 2 But, CR 7 , N, O, or S; Z 1 But, CR 8 or N, Z 2 But, CR 9 or N, Z 3 But, CR 10 or N, Z 4が , C.R. 11 or N, R 6 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Alkylene P(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 and SO2R 12 , C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from halogen, CN, C 1~8 Alkoxy, C 1~8Alkylamino, C 1~8 Alkyl sulfonyl, CO2R 12 , C(O)N(R 12 )2, OR 12 , N(R 12 )2, NO2, SR 12 , and SO2R 12 each optionally substituted with one or more substituents independently selected from The C in question 3~6 Cycloalkyl, C 6~9 Alkylenecycloalkyl, C 3~6 Heterocyclyl, C 6~9 Alkyleneheterocycloalkyl, C 4~7 Heterocyclyl, C 7~10 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 12 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 12 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 , R 8 , R 9 , R 10 , and R 11 But 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, C2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is selected from 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 The alkylene heteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 But hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 The alkylene heteroaryl is selected from 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or X 2 is CR 7 If R 7 , and R 1 , R 2 or R3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; Or X 1 NR 6 and X 2 is CR 7 If R 6 and R 7 These are combined with the atoms to which they are bonded to form C 4~10 Heterocycloalkyl or C 5~10 forming a heteroaryl, The C in question 4~10 Heterocycloalkyl and C 5~10 Heteroaryl is 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 , SO2R14 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2 is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z 4 is CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 These are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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 , SO2R14 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 But hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X 2 , Z 1 , Z 2 , Z 3 , and Z 4 is a heteroatom, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

[0208] In some embodiments, the compound of formula (I) is:

[0209] [ka] None of the above.

[0210] In some embodiments, X 2 , Z 1 , Z 2 , Z 3 , and Z 4 is a heteroatom. The remainder all represent ring carbon atoms as defined for each variable herein. In these embodiments, the 6,5-fused bicyclic core of the compound of Formula (I) has two heteroatoms.

[0211] In some embodiments, X 1 , X 2 , Z 1 , Z 2 , Z 3 , and Z 4 is defined by the first to sixth embodiments.

[0212] [Table 1] In some embodiments, X 1 , X 2 , Z 1 , Z 2 , Z 3 , and Z 4is as described in any one of the above embodiments 1 to 4.

[0213] In some embodiments, X 1 is NR 6 is.

[0214] In some embodiments, R 6 (if present) is H.

[0215] In some embodiments, R 6 (if present) C 1~6 Alkyl, preferably C 1~4 It is alkyl.

[0216] In some embodiments, X 1 is NR 6 and R 6 is H.

[0217] In some embodiments, R 8 and R 9 One of (if present) is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl, and the other (if present) is hydrogen.

[0218] In some embodiments, R 8 (if present) halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl; R 9 (if present) is hydrogen.

[0219] In some embodiments, R 9 (if present) halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6Alkyl, and C 1~6 haloalkyl; R 8 (if present) is hydrogen.

[0220] In some embodiments, R 8 (if present) halogen, OR 13 , and C 1~6 alkyl, and R 9 (if present) is hydrogen.

[0221] In some embodiments, R 9 (if present) halogen, OR 13 , and C 1~6 alkyl, and R 8 (if present) is hydrogen.

[0222] In some embodiments, Z 1 is CR 8 is.

[0223] In some embodiments, Z 2 is CR 9 is.

[0224] In some embodiments, Z 1 is CR 8 and R 8 is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl.

[0225] In some embodiments, Z 2 is CR 9 and R 9 is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl.

[0226] In some embodiments, Z 1 is CR 8 and R 8 is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl; Z 2 is N or CH.

[0227] In some embodiments, Z 2 is CR 9 and R 9 is halogen, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, and C 1~6 haloalkyl; Z 1 is N or CH.

[0228] In some embodiments, Z 3 is CR 10 and preferably R 10 is H.

[0229] In some embodiments, R 8 and R 9 One of the two is OR 13 is.

[0230] In some embodiments, Z 1 One or both of the following is CR 8 and / or Z 2 is CR 9 is.

[0231] In some embodiments, each R 13 (if present) hydrogen and C 1~6 alkyl.

[0232] In some embodiments, each R 13 (if present) is H.

[0233] In some embodiments, each R 13 (if present) C 1~6 Alkyl, preferably C 1~4 It is preferably alkyl, more preferably methyl.

[0234] In some embodiments, X 2 is CR 7 is.

[0235] In some embodiments, R 7 (if present) is hydrogen.

[0236] In some embodiments, Z 1 is CR 8 is.

[0237] In some embodiments, R 8 (if present) is hydrogen.

[0238] In some embodiments, Z 2 is CR 9 is.

[0239] In some embodiments, R 9 (if present) is hydrogen.

[0240] In some embodiments, Z 3 is CR 10 is.

[0241] In some embodiments, R 10 (if present) is hydrogen.

[0242] In some embodiments, Z 4 is CR 11 is.

[0243] In some embodiments, R 11 (if present) is hydrogen.

[0244] In some embodiments, R7 , R 10 , and R 11 (when present) are each hydrogen.

[0245] In some embodiments, R 6 , R 7 , R 10 , and R 11 (when present) are each hydrogen.

[0246] In some embodiments, R 8 , R 9 , R 10 , and R 11 (if present) is other than hydrogen. 8 , R 9 , R 10 , and R 11 R out of (if present) 8 In some embodiments, only R 8 , R 9 , R 10 , and R 11 R out of (if present) 9 In some embodiments, only R 8 , R 9 , R 10 , and R 11 R out of (if present) 10 In some embodiments, only R 8 , R 9 , R 10 , and R 11 R out of (if present) 11 Only is other than hydrogen.

[0247] In some embodiments, R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 (if present) is other than hydrogen. 6 , R 7 , R 8 , R9 , R 10 , and R 11 R out of (if present) 6 In some embodiments, only R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 R out of (if present) 7 In some embodiments, only R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 R out of (if present) 8 In some embodiments, only R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 R out of (if present) 9 In some embodiments, only R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 R out of (if present) 10 In some embodiments, only R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 R out of (if present) 11 Only is other than hydrogen.

[0248] In some embodiments, R 1 and R 2 In some embodiments, at least one of R 1 and R 2 are not both methyl.

[0249] In some embodiments, the compound of formula (I) has formula (II):

[0250] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, SR4 , and SO2R 4 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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 2~6Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question5~8 Heterocyclylalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; Z 1 is CR 8 or N, Z 2 is CR 9 or N, Z 3 is CR 10 or N, Z 4 is CR 11 or N, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R13 , 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, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2 is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z4 is CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Z 1 , Z 2 , Z 3 , and Z 4 One or more of is N.

[0251] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0252] In some embodiments, R 1 and R 2 is C1~4 alkyl.

[0253] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0254] [ka] Form one of the following:

[0255] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0256] In some embodiments, R 3 is hydrogen.

[0257] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0258] In some embodiments, R 7 , R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0259] In some embodiments, R 7 , R 8 R 9 , R 10 , and R 11is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 1~6 Alkylene P(O)(OR 13 )2, S(O)R 13 , S(O)N(R 13 )2, N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0260] In some embodiments, R 7 , R 8 , R 9 , R 10 , and R 11 When present, one or two of the groups are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0261] In some embodiments, R 8 and R 9 When present, they combine with the atoms to which they are attached to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0262] In some embodiments, R 8 and R 9 are combined to:

[0263] [ka] C selected from5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0264] In some embodiments, R 8 and R 9 are combined to:

[0265] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0266] In some embodiments, the compound of Formula (I) has the formula (IIa):

[0267] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is hydrogen, C 1~6 Alkyl, C 3~8 Cycloalkyl, or C4~14 alkylenecycloalkyl; Alternatively, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 1~6 Alkylene P(O)(OR13 )2, S(O)R 13 , S(O)N(R 13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 13and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is a group that includes 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, C2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl;

[0268] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0269] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0270] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0271] [ka] Form one of the following:

[0272] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0273] In some embodiments, R 3 is hydrogen.

[0274] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0275] In some embodiments, R 7 , R 9 , R 10 , and R 11 is hydrogen, halogen, CN, OR13 , 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0276] In some embodiments, R 7 , R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0277] In some embodiments, R 7 , R 9 , R 10 , and R 11 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 9 , R 10 , and R 11 The other of each is hydrogen.

[0278] In some embodiments, the compound of Formula (II) has the formula (IIb):

[0279] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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(R4 )2, NO2, SR 4 , SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 1~6Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; R 8 , R 10 , and R 11 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 10 and R11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl;

[0280] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0281] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0282] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0283] [ka] Form one of the following:

[0284] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0285] In some embodiments, R 3 is hydrogen.

[0286] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes halogen, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C1~8 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0287] In some embodiments, R 7 , R 8 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13, OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0288] In some embodiments, R 7 , R 8 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0289] In some embodiments, R 7 , R 8 , R 10 , and R 11 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 , R 10 , and R 11 The other of each is hydrogen.

[0290] In some embodiments, the compound of Formula (I) has the formula (IIc):

[0291] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13)2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is a group that includes halogen, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; R 8 , R 9 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 1~6 Alkylene P(O)(OR 13 )2, S(O)R 13 , S(O)N(R13 )2, SO2R 13 , N(R 13 )2, N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 9 and R 9 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl;

[0292] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0293] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0294] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0295] [ka] Form one of the following:

[0296] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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 2~6Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0297] In some embodiments, R 3 is hydrogen.

[0298] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0299] In some embodiments, R 7 , R 8 , R 9 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0300] In some embodiments, R 7 , R 8 , R 9 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0301] In some embodiments, R 7 , R 8 , R 9 , and R 11 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 , R 9 , and R 11 The other of each is hydrogen.

[0302] In some embodiments, the compound of Formula (I) has the formula (IId):

[0303] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 Alkyl sulfonyl, CO2R5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 , and SO2R 5 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 7 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 7 , and R 1 , R 2 or R 3 One of these will combine with the atom to which it is attached to form C 5~8 forming a heterocycloalkyl, The C in question 5~8 Heterocyclylalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with one or more substituents selected from heterocycloalkyl; R 8 , R 9 , and R 10 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 8 and R 9 , or R 9 and R 10 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl;

[0304] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0305] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0306] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0307] [ka] Form one of the following:

[0308] 7 In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0309] In some embodiments, R 3 is hydrogen.

[0310] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0311] In some embodiments, R 7 , R 8 , R 9 , and R 10 is 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, C 2~6Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0312] In some embodiments, R 7 , R 8, R 9 , and R 10 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0313] In some embodiments, R 7 , R 8 , R 9 , and R 10 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 7 , R 8 , R 9 , and R 10 The other of each is hydrogen.

[0314] In some embodiments, the compound of Formula (I) has Formula (III):

[0315] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Z 1is CR 8 or N, Z 2 is CR 9 or N, Z 3 is CR 10 or N, Z 4 is CR 11 or N, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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, C3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2 is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z 4 is CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Z 1 , Z 2 , Z 3 , and Z 4 One or more of is N.

[0316] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0317] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0318] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0319] [ka] Form one of the following:

[0320] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with halogen, CN, C 1~8 Alkoxy, C1~8 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0321] In some embodiments, R 3 is hydrogen.

[0322] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0323] In some embodiments, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0324] In some embodiments, R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 1~6 Alkylene P(O)(OR 13 )2, S(O)R 13 , SO2R 13 , N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0325] In some embodiments, R 8 , R 9 , R 10 , and R 11 When present, one or two of the groups are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0326] In some embodiments, R 8 and R 9 When present, they combine with the atoms to which they are attached to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0327] In some embodiments, R 8 and R 9 are combined to:

[0328] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0329] In some embodiments, R 8 and R 9 are combined to:

[0330] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0331] In some embodiments, the compound of Formula (I) has the formula (IIIa):

[0332] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes halogen, (O), 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 , SO2R 4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 2~6Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Z 1 , Z 2 , Z 3 , and Z 4 One or more of is N.

[0333] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0334] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0335] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0336] [ka] Form one of the following:

[0337] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0338] In some embodiments, R 3 is hydrogen.

[0339] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0340] In some embodiments, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13is as defined in any one of the preceding paragraphs.

[0341] In some embodiments, R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0342] In some embodiments, R 8 , R 9 , R10 , and R 11 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0343] In some embodiments, R 8 and R 9 are combined with the atoms to which they are bonded to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0344] In some embodiments, R 8 and R 9 are combined to:

[0345] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0346] In some embodiments, R 8 and R 9 are combined to:

[0347] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0348] In some embodiments, the compound of formula (I) has formula (IV):

[0349] [ka] wherein X2 is O or S; R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C 1~4 selected from alkylene, C2-C4 alkenylene, and C2-C4 alkynylene; Z 1 is CR 8 or N, Z 2 is CR 9 or N, Z 3 is CR 10 or N, Z 4 is CR 11 or N, R 8 , R 9 , R 10 , and R 11 is hydrogen, halogen, CN, OR 13 , N(R 13 )2, SR 13 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or Z 1 is CR 8 and Z 2is CR 9 If Z is 2 is CR 9 and Z 3 is CR 10 If Z is 3 is CR 10 and Z 4 is CR 11 If R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X 2 , Z 1 , Z 2 , Z 3 , and Z 4 One or more of is a heteroatom.

[0350] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0351] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0352] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0353] [ka] Form one of the following:

[0354] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0355] In some embodiments, R 3 is hydrogen.

[0356] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0357] In some embodiments, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13is as defined in any one of the preceding paragraphs.

[0358] In some embodiments, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0359] In some embodiments, R 8 , R 9 , R10 , and R 11 When present, one or two of the groups are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0360] In some embodiments, R 8 and R 9 When present, they combine with the atoms to which they are attached to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0361] In some embodiments, R 8 and R 9 are combined to:

[0362] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0363] In some embodiments, R 8 and R 9 are combined to:

[0364] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0365] In some embodiments, X 2 is O.

[0366] In some embodiments, the compound of Formula (I) has the formula (IVa):

[0367] [ka] wherein R1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8 forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7 Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13)2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 13 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Alternatively, R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are bonded to form C 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, or C 5~10 forming a heteroaryl, The C in question 4~8 Cycloalkyl, C 5~8 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 14 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; Each R 14 is hydrogen, C 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C 3~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8Alkyl 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl;

[0368] In some embodiments, R 1 and R 2 is C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, and C 4~14 alkylenecycloalkyl.

[0369] In some embodiments, R 1 and R 2 is C 1~4 alkyl.

[0370] In some embodiments, R 1 and R 2 together with the nitrogen to which they are attached, form:

[0371] [ka] Form one of the following:

[0372] In some embodiments, R 1 and R 2 are combined with the atoms to which they are bonded to form C 3~6 Forming a heterocycloalkyl, the C 3~6 Heterocycloalkyl is a group that is substituted with 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0373] In some embodiments, R 3 is hydrogen.

[0374] In some embodiments, R 3 , and R 1 and R 2 One of them combines with the atom to which it is attached to form C 3~8 Forming a heterocycloalkyl, the C 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 heterocycloalkyl, wherein R 4 is defined in one of the preceding paragraphs.

[0375] In some embodiments, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 13and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 13 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0376] In some embodiments, R 8 R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)N(R 13 )2, OC(O)R 13 , OSO2R 13, OP(O)(OR 13 )2, O.C. 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 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with halogen, CN, C 1~8 Alkoxy, C 1~8 Alkylamino, C 1~8 optionally substituted with one or more substituents independently selected from alkylsulfonyl, COH, COCH, C(O)NH, C(O)N(CH), C(O)NHCH, OH, NH, N(CH), NO, NHCH, SH, SCH, SOCH, and SOCH; The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally further substituted with a substituent selected from heterocycloalkyl; In the formula, R 13 is as defined in any one of the preceding paragraphs.

[0377] In some embodiments, R 8 , R 9 , R 10 , and R 11 One or two of them are halogen, C 1~6 Alkyl, C 1~6 Haloalkyl and OR 13 wherein R 13 is C 1~6 Alkyl and C 1~6 haloalkyl; R 8 R 9 , R 10 , and R 11 The other of each is hydrogen.

[0378] In some embodiments, R 8 and R 9 are combined with the atoms to which they are bonded to form C 5~8 Heterocycloalkyl or C 5~10 Forming a heteroaryl, the C 5~8 Heterocycloalkyl and C 5~10Heteroaryl is a group that includes halogen, (O), 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, C 2~6 Haloalkynyl, C 3~6 C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 Each is further optionally substituted with a substituent selected from heterocycloalkyl.

[0379] In some embodiments, R 8 and R 9 are combined to:

[0380] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 represents a covalent bond with the aromatic ring to which it is attached, The C in question 5~8 Heterocycloalkyl and C 5~10 Heteroaryl is a halogen atom, (O), CN, 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, and C 1~6 each further optionally substituted with a substituent selected from haloalkyl.

[0381] In some embodiments, R 8 and R 9 are combined to:

[0382] [ka] C selected from 5~8 Heterocycloalkyl or C 5~10 form a heteroaryl, where the dashed bond is R 8 and R 9 indicates a covalent bond with the aromatic ring to which it is attached.

[0383] In some embodiments, the compound of formula (I) has formula (V):

[0384] [ka] wherein R 1 and R 2 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~8 Cycloalkyl, C 4~14Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is substituted with 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 each optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 4~14 Alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C 14 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 6~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Alternatively, R 1 and R 2 combine with the atoms to which they are attached to form O, S, S(O), SO2, N, and NR 4 C containing one or two additional ring hetero moieties selected from 3~8forming a heterocycloalkyl, The C in question 3~8 Heterocycloalkyl is a group that includes 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, C 2~6 Haloalkynyl, C 1~8 Alkylamino, C 1~8 Alkylsulfonyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; R 3 is 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 atom to which it is attached to form C 3~12 forming a heterocycloalkyl, The C in question 3~12 Heterocycloalkyl is a group that includes 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 , SO2R4 , C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, N, S(O), SO2 and NR 4 C containing one or two ring hetero moieties selected from 3~6 and optionally further substituted with substituents selected from heterocycloalkyl; Each R 4 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~7 heterocycloalkyl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~7 Cycloalkyl, and C 3~7 Heterocycloalkyl is a group that is substituted with 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 each optionally substituted with one or more substituents independently selected from The C3-C7 cycloalkyl and C 3~7Heterocycloalkyl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 3~6 Cycloalkyl, as well as O, S, S(O), SO2, N, and NR 5 C containing one or two ring hetero moieties selected from 3~6 each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R 5 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 heteroaryl; The C in question 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 1~6 Haloalkyl, C 3~8 Cycloalkyl, C 5~10 Heterocycloalkyl, C 6~12 Aryl, and C 5~10 Heteroaryl is a group containing 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, C 2~6 Haloalkynyl, C 3~6C containing cycloalkyl and one or two ring hetero moieties selected from O, S, S(O), SO, N, NH, and NCH 3~6 each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Z 1 is CR 8 or N, Z 2 is CR 9 or N, Z 3 is CR 10 or N, Z 4 is CR 11 or N, R 8 , R 9 , R 10 , and R 11 is 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, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, CO2R 13 , C(O)R 13 , C(O)N(R 13 )2, C(O)C(O)N(R 13 )2, OC(O)R 13 ,OC(O)OR 13 , OC(O)N(R 13 )2, OS(O)R 13 , OS(O)N(R 13 )2, OSO2R 13 , OP(O)(OR 13 )2, O.C. 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(R13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 )2, NO2, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, C 4~16 alkyleneheteroaryl; The C in question 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C2-C6 haloalkenyl, C 2~6 Alkynyl, C 2~6 Haloalkynyl, C 1~6 Alkylamines, C 1~6 Alkoxy, C 1~6 Haloalkoxy, C 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C 3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is substituted with 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 and optionally substituted with one or more substituents independently selected from The C in question 3~8 Cycloalkyl, C 3~14 Alkylenecycloalkyl, C3~10 Heterocycloalkyl, C 4~16 Alkyleneheterocycloalkyl, C 6~12 Aryl, C 7~18 Alkylene aryl, C 5~10 Heteroaryl, and C 4~16 Alkyleneheteroaryl is (O), C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Haloalkenyl, C 2~6 Alkynyl,...

Claims

1. Formula (I): 【Chemistry 1】 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, During the ceremony, R １ and R ２ But hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , and SO ２ R ４ each optionally substituted with one or more substituents independently selected from Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Or, R １ and R ２ are combined with the atoms to which they are bonded to form O, S, S(O), SO ２ , N, and NR ４ C containing one or two additional ring hetero moieties selected from ３～８ forming a heterocycloalkyl, Said C ３～８ Heterocycloalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , S.O. ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～８ Alkylamino, C １～８ Alkylsulfonyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with substituents selected from heterocycloalkyl; R ３ But hydrogen, C １～６ Alkyl, C ３～８ cycloalkyl, or C ４～１４ alkylenecycloalkyl; Or, R ３ , and R １ and R ２ In combination with the atom to which they are attached, one of ３～１２ forming a heterocycloalkyl, Said C ３～１２ Heterocycloalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , S.O. ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with substituents selected from heterocycloalkyl; Each R ４ But hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, as well as O, S, S(O), SO ２ , N and NR ５ C containing one or two ring hetero moieties selected from ３～７ heterocycloalkyl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, and C ３～７ Heterocycloalkyl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ５ , C(O)N(R ５ ) ２ , OR ５ , N(R ５ ) ２ , NO ２ , S.R. ５ , and SO ２ R ５ each optionally substituted with one or more substituents independently selected from Said C ３ ~C ７ Cycloalkyl and C ３～７ Heterocycloalkyl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N and NR ５ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R ５ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ heteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C １～４ Alkylene, C ２ ~C ４ Alkenylene, and C ２ ~C ４ alkynylene, X １ But N, NR ６ , O, or S; X ２ But, CR ７ , N, O, or S; Z １ But, CR ８ or N, Z ２ But, CR ９ or N, Z ３ But, CR １０ or N, Z ４ But, CR １１ or N, R ６ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkylene P(O)(OR １２ ) ２ , C(O)R １２ , CO ２ R １２ , C(O)N(R １２ ) ２ , S(O)R １２ and SO ２ R １２ , C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １２ , C(O)N(R １２ ) ２ , OR １２ , N(R １２ ) ２ , NO ２ , S.R. １２ , and SO ２ R １２ each optionally substituted with one or more substituents independently selected from Said C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １２ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R １２ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R ７ , R ８ , R ９ , R １０ , and R １１ But hydrogen, halogen, CN, OR １３ , N(R １３ ) ２ , S.R. １３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２ ~C ６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～６ Alkylamines, C １～６ Alkoxy, C １～６ Haloalkoxy, CO ２ R １３ , C(O)R １３ , C(O)N(R １３ ) ２ , C(O)C(O)N(R １３ ) ２ , O.C.(O.)R １３ , OC(O)OR １３ , OC(O)N(R １３ ) ２ , OS(O)R １３ , OS(O)N(R １３ ) ２ , OSO ２ R １３ , OP(O)(OR １３ ) ２ , O.C. １～６ Alkylene P(O)(OR １３ ) ２ , S(O)R １３ , S(O)N(R １３ ) ２ , S.O. ２ R １３ , N(R １３ ) ２ , N(R １３ ) C(O)R １３ , N(R １３ )C(O)OR １３ , N(R １３ )C(O)N(R １３ ) ２ , NO ２ , C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, C ４～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２ ~C ６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～６ Alkylamines, C １～６ Alkoxy, C １～６ Haloalkoxy, C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ４～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １３ , C(O)N(R １３ ) ２ , OR １３ , N(R １３ ) ２ , NO ２ , S.R. １３ , and SO ２ R １３ and optionally substituted with one or more substituents independently selected from Said C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ４～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, and NR １３ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Each R １３ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or, X ２ is CR ７ If R ７ , and R １ , R ２ or R ３ One of these is combined with the atom to which it is attached to form C ５～８ can form a heterocycloalkyl, Said C ５～８ Heterocyclylalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with one or more substituents selected from heterocycloalkyl; Or, X １ NR ６ and X ２ is CR ７ If R ６ and R ７ These are combined with the atoms to which they are bonded to form C ４～１０ Heterocycloalkyl or C ５～１０ can form a heteroaryl, Said C ４～１０ Heterocycloalkyl and C ５～１０ Heteroaryl is halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Or Z １ is CR ８ and Z ２ is CR ９ or Z ２ is CR ９ and Z ３ is CR １０ or Z ３ is CR １０ and Z ４ is CR １１ If R ８ and R ９ , or R ９ and R １０ , or R １０ and R １１ These are combined with the atoms to which they are bonded to form C ４～８ Cycloalkyl, C ５～８ Heterocycloalkyl, C ６～１２ Aryl, or C ５～１０ can form a heteroaryl, Said C ４～８ Cycloalkyl, C ５～８ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Each R １４ But hydrogen, C １～６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C １ ~C ６ Haloalkyl, C ３ ~C ７ Cycloalkyl, C ３～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ heteroaryl; Said C １～６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C １ ~C ６ Haloalkyl, C ３ ~C ７ Cycloalkyl, C ３～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NO ２ , NHCH ３ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X ２ , Z １ , Z ２ , Z ３ , and Z ４ is a heteroatom; The compound of formula (I) is 【Chemistry 2】 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, which is not any of:

2. X ２ , Z １ , Z ２ , Z ３ , and Z ４ 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein one of is a heteroatom.

3. X １ , X ２ , Z １ , Z ２ , Z ３ , and Z ４ is defined by any one of embodiments 1-6, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof. Table 1

4. X １ , X ２ , Z １ , Z ２ , Z ３ , and Z ４ is as defined in any one of embodiments 1-4, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

5. X １ NR ６ 2. The compound of claim 1, wherein:

6. R ６ 10. The compound of claim 1, wherein (if present) is H, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

7. R ８ and R ９ (when present) is halogen, OR １３ , N(R １３ ) ２ , S.R. １３ , C １～６ Alkyl, and C １～６ haloalkyl; and the other, if present, is hydrogen; or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

8. Each R １３ (if present) is hydrogen and C １～６ 8. The compound of claim 7, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein:

9. R ７ , R １０ , and R １１ 8. The compound of claim 7, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein (when present) is hydrogen.

10. R １ and R ２ But C １～４ 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein each independently is selected from: alkyl.

11. R １ and R ２ These, together with the nitrogen to which they are attached, form the following: 【Transformation 3】 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, which forms any one of:

12. R ３ 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein is hydrogen.

13. 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, wherein L is methylene. 【Request Item 14】 【Table 2-1】 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, selected from:

15. A pharmaceutical comprising the compound of any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof.

16. 15. A pharmaceutical composition comprising the compound of any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, and a pharmaceutically acceptable excipient.

17. 1. A compound of formula (I): 【Chemistry 4】 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof, During the ceremony, R １ and R ２ But hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , and SO ２ R ４ each optionally substituted with one or more substituents independently selected from Said C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ４ ~C １４ Alkyleneheterocycloalkyl, C ３ ~C ８ Heterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Or, R １ and R ２ are combined with the atoms to which they are bonded to form O, S, S(O), SO ２ , N, and NR ４ C containing one or two additional ring hetero moieties selected from ３～８ forming a heterocycloalkyl, Said C ３～８ Heterocycloalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , S.O. ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～８ Alkylamino, C １～８ Alkylsulfonyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with substituents selected from heterocycloalkyl; R ３ But hydrogen, C １～６ Alkyl, C ３～８ cycloalkyl, or C ４～１４ alkylenecycloalkyl; Or, R ３ , and R １ and R ２ In combination with the atom to which they are attached, one of ３～１２ forming a heterocycloalkyl, Said C ３～１２ Heterocycloalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ４ , C(O)N(R ４ ) ２ , OR ４ , N(R ４ ) ２ , NO ２ , S.R. ４ , S.O. ２ R ４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR ４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with substituents selected from heterocycloalkyl; Each R ４ But hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, as well as O, S, S(O), SO ２ , N and NR ５ C containing one or two ring hetero moieties selected from ３～７ heterocycloalkyl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～７ Cycloalkyl, and C ３～７ Heterocycloalkyl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R ５ , C(O)N(R ５ ) ２ , OR ５ , N(R ５ ) ２ , NO ２ , S.R. ５ , and SO ２ R ５ each optionally substituted with one or more substituents independently selected from Said C ３ ~C ７ Cycloalkyl and C ３～７ Heterocycloalkyl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N and NR ５ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R ５ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ heteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ５～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; L is C １～４ Alkylene, C ２ ~C ４ Alkenylene, and C ２ ~C ４ alkynylene, X １ But N, NR ６ , O, or S; X ２ But, CR ７ , N, O, or S; Z １ But, CR ８ or N, Z ２ But, CR ９ or N, Z ３ But, CR １０ or N, Z ４ But, CR １１ or N, R ６ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Alkylene P(O)(OR １２ ) ２ , C(O)R １２ , CO ２ R １２ , C(O)N(R １２ ) ２ , S(O)R １２ and SO ２ R １２ , C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １２ , C(O)N(R １２ ) ２ , OR １２ , N(R １２ ) ２ , NO ２ , S.R. １２ , and SO ２ R １２ each optionally substituted with one or more substituents independently selected from Said C ３～６ Cycloalkyl, C ６～９ Alkylenecycloalkyl, C ３～６ Heterocyclyl, C ６～９ Alkyleneheterocycloalkyl, C ４～７ Heterocyclyl, C ７～１０ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １２ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with substituents independently selected from heterocycloalkyl; Each R １２ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; R ７ , R ８ , R ９ , R １０ , and R １１ But hydrogen, halogen, CN, OR １３ , N(R １３ ) ２ , S.R. １３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２ ~C ６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～６ Alkylamines, C １～６ Alkoxy, C １～６ Haloalkoxy, CO ２ R １３ , C(O)R １３ , C(O)N(R １３ ) ２ , C(O)C(O)N(R １３ ) ２ , O.C.(O.)R １３ , OC(O)OR １３ , OC(O)N(R １３ ) ２ , OS(O)R １３ , OS(O)N(R １３ ) ２ , OSO ２ R １３ , OP(O)(OR １３ ) ２ , O.C. １～６ Alkylene P(O)(OR １３ ) ２ , S(O)R １３ , S(O)N(R １３ ) ２ , S.O. ２ R １３ , N(R １３ ) ２ , N(R １３ ) C(O)R １３ , N(R １３ )C(O)OR １３ , N(R １３ )C(O)N(R １３ ) ２ , NO ２ , C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, C ４～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２ ~C ６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C １～６ Alkylamines, C １～６ Alkoxy, C １～６ Haloalkoxy, C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ４～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １３ , C(O)N(R １３ ) ２ , OR １３ , N(R １３ ) ２ , NO ２ , S.R. １３ , and SO ２ R １３ and optionally substituted with one or more substituents independently selected from Said C ３～８ Cycloalkyl, C ３～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ４～１６ The alkylene heteroaryl is (O), C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, and NR １３ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Each R １３ But hydrogen, C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ alkyleneheteroaryl; Said C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C １～６ Haloalkyl, C ３～８ Cycloalkyl, C ４～１４ Alkylenecycloalkyl, C ３～１０ Heterocycloalkyl, C ４～１６ Alkyleneheterocycloalkyl, C ６～１２ Aryl, C ７～１８ Alkylene aryl, C ５～１０ Heteroaryl, and C ６～１６ The alkylene heteroaryl is selected from halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; Or, X ２ is CR ７ If R ７ , and R １ , R ２ or R ３ One of these is combined with the atom to which it is attached to form C ５～８ forming a heterocycloalkyl, Said C ５～８ Heterocyclylalkyl is selected from halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ and optionally further substituted with one or more substituents selected from heterocycloalkyl; Or, X １ NR ６ and X ２ is CR ７ If R ６ and R ７ These are combined with the atoms to which they are bonded to form C ４～１０ Heterocycloalkyl or C ５～１０ forming a heteroaryl, Said C ４～１０ Heterocycloalkyl and C ５～１０ Heteroaryl is halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Or Z １ is CR ８ and Z ２ is CR ９ or Z ２ is CR ９ and Z ３ is CR １０ or Z ３ is CR １０ and Z ４ is CR １１ If R ８ and R ９ , or R ９ and R １０ , or R １０ and R １１ These are combined with the atoms to which they are bonded to form C ４～８ Cycloalkyl, C ５～８ Heterocycloalkyl, C ６～１２ Aryl, or C ５～１０ forming a heteroaryl, Said C ４～８ Cycloalkyl, C ５～８ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, (O), CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ R １４ , C(O)N(R １４ ) ２ , OR １４ , N(R １４ ) ２ , NO ２ , S.R. １４ , S.O. ２ R １４ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, N, S(O), SO ２ and NR １４ C containing one or two ring hetero moieties selected from ３～６ each optionally further substituted with a substituent selected from heterocycloalkyl; Each R １４ But hydrogen, C １～６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C １ ~C ６ Haloalkyl, C ３ ~C ７ Cycloalkyl, C ３～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ heteroaryl; Said C １～６ Alkyl, C ２ ~C ６ Alkenyl, C ２ ~C ６ Alkynyl, C １ ~C ６ Haloalkyl, C ３ ~C ７ Cycloalkyl, C ３～１０ Heterocycloalkyl, C ６～１２ Aryl, and C ５～１０ Heteroaryl is halogen, CN, C １～８ Alkoxy, C １～８ Alkylamino, C １～８ Alkyl sulfonyl, CO ２ H, CO ２ CH ３ , C(O)NH ２ , C(O)N(CH ３ ) ２ , C(O)NHCH ３ , OH, NH ２ , N(CH ３ ) ２ , NHCH ３ , NO ２ , S.H., S.C.H. ３ , S.O. ２ CH ３ , SOCH ３ , C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Haloalkenyl, C ２～６ Alkynyl, C ２～６ Haloalkynyl, C ３～６ Cycloalkyl, as well as O, S, S(O), SO ２ , N, NH and NCH ３ C containing one or two ring hetero moieties selected from ３～６ each optionally substituted with one or more substituents independently selected from heterocycloalkyl; X ２ , Z １ , Z ２ , Z ３ , and Z ４ wherein one or more of is a heteroatom.

18. Treating a psychosis. Treating diseases, disorders or conditions of the central nervous system (CNS) and / or nervous system; and Increasing neuroplasticity and / or increasing dendritic spine density; The pharmaceutical composition according to claim 17, for one of the following:

19. The pharmaceutical composition according to claim 17, wherein the compound of formula (I) or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph, or prodrug thereof is a compound according to any one of claims 1 to 14.

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