Novel functionalized lactams as modulators of 5-hydroxytryptamine receptor 7 and their method of use

Abstract

To provide novel functionalized lactams as modulators of the 5-hydroxytryptamine receptor 7 and methods of using the same.SOLUTION: Described herein are new, selective modulators of the 5-HT7 receptor. These selective compounds may be useful for the treatment of CNS and non-CNS indications. The compounds described herein may be selective in targeting 5-HT7 receptors as compared to other receptors and / or by selectively targeting 5-HT7 receptors expressed in certain tissues or organs, thereby providing effective selectivity through a particular partitioning profile of the 5-HT7 modulator.SELECTED DRAWING: None

Description

[Technical Field]

[0001] 1. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 934,997, filed November 13, 2019, which is incorporated by reference in its entirety.

[0002] 2. STATEMENT OF FEDERALLY FUNDED RESEARCH This invention is based on the findings of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDD). This invention was made with government support under Grant No. 2R44DK115254-02A1 awarded by the National Institute for Clinical Oncology, the National Institutes of Health ...

[0003] 3. Introduction Embodiments of the present invention are directed to novel compounds useful as modulators of 5-hydroxytryptamine receptor 7 (5-HT7) activity and methods of use thereof. Embodiments are further directed to novel chemotypes useful in the treatment of diseases associated with dysregulation of 5-hydroxytryptamine receptor 7 activity. [Background technology]

[0004] 4.Background Serotonin, discovered in the late 1940s, is present in both the peripheral and central nervous systems [Physiol.Res,60(2011)15-25; Psychopharmacology 213(2011)167-169]. Serotonin, also known as 5-hydroxytryptamine (5-HT), is an indolealkylamine monoamine neurotransmitter that acts at neuronal synapses. Seven distinct families of serotonin receptors have been identified, and at least 20 subgroups have been cloned based on sequence similarity, signaling binding, and pharmacological properties. The seven 5-HT receptor families are named 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7, and each of these receptors has its own subfamilies or subgroups. The signaling mechanisms of all seven families have been studied, and it has been found that activation of 5-HT1 and 5-HT5 receptors leads to a decrease in intracellular cAMP, while activation of 5-HT2, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors leads to an increase in intracellular IP3 and DAG. The 5-HT pathway in the brain is an important target for drug development in the field of CNS disorders. This neurotransmitter binds to G protein-coupled receptors and is involved in a wide variety of behaviors, including cognition, mood, anxiety, attention, appetite, cardiovascular function, vasoconstriction, sleep (ACS Medicinal Chemistry Letters, 2011, 2, 929-932; Physiological Research, 2011, 60, 15-25), inflammatory bowel disease (IBD) and enteritis (WO 2012058769; Khan, W.I., et al. Journal of Immunology, 2013, 190, 4795-4804), epilepsy and seizure disorders (Epilepsy Research (2007) 75, 39), and drug and alcohol addiction (Hauser, et al. Frontiers in Neuroscience, 2015, 8, 1-9), among others. Described herein are novel selective modulators of the 5-HT7 receptor. These selective compounds may be useful in treating CNS and non-CNS indications. The compounds described herein exhibit potent therapeutic effects in targeting the 5-HT7 receptor by selectively targeting the 5-HT7 receptor relative to other receptors and / or expressed in specific tissues or organs. It can be selective for 5-HT7 modulators, thereby effectively selecting through the specific cleavage profile of the 5-HT7 modulator. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2012 / 058769 [Non-patent literature]

[0006] [Non-Patent Document 1] ACS Medicinal Chemistry Letters,2011,2,929-932;Physiological Research,2011,60,15-25 [Non-patent document 2] Khan,WI,et al.Journal of Immunology,2013,190,4795-4804 [Non-patent document 3] Hauser,et al.Frontiers in Neuroscience,2015,8,1-9 Summary of the Invention [Means for solving the problem]

[0007] 5. Summary of the Invention In one aspect, the invention features a compound having a structure according to the following general formula (I'): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N1’ is hydrogen or C1-C7 alkyl, R 1N are imidazoles, oxazoles, isoxazoles, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8boptionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R AA are each independently a C1-C7 linear alkyl; R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; aa is 0, 1, or 2; y 1 is 0, 1, or 2, and In the formula, R 5 is unsubstituted C1-C7 alkyl or unsubstituted C3-C7 cycloalkyl, and R N1 is hydrogen, then aa is 1 or 2. In another aspect, the invention features a compound having a structure according to the following general formula (I'-N): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N1’ is hydrogen or C1-C7 alkyl, R 1N-N C6~C 10 Heteroaryl, 5- to 10-membered heteroaryl, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8aand R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R AA are each independently a C1-C7 linear alkyl; R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; aa is 0, 1, or 2; y 1 is 0, 1, or 2, and In the formula, R 5 is unsubstituted C1-C7 alkyl or unsubstituted C3-C7 cycloalkyl, and R N1 is hydrogen, then aa is 1 or 2.

[0008] In embodiments, the compound of general formula (I') or (I'-N) has a structure according to general formula (I'-1): [ka] It is intended to include enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof.

[0009] In embodiments, the compound of general formula (I') or (I'-N) has a structure according to general formula (I'-2): [ka] It is intended to include enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof.

[0010] In embodiments, the compound of general formula (I'-N) has a structure according to general formula (I'-3): [ka] It is intended to include enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof.

[0011] In embodiments, R 1N teeth, [ka] In the formula, R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 containing a group selected from forming a heterocycle containing 3 to 7 atoms, and R9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; [ka] is.

[0012] In embodiments, R 1N teeth, [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8h is unsubstituted C1-C7 alkyl, or [ka] is.

[0013] In embodiments, R 1N is: [ka] In the formula, R 8a and R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is unsubstituted C1-C7 alkyl, [ka] In the formula, R 4a and R 8gare each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8a and R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h are independently unsubstituted C1-C7 alkyl; or [ka] .

[0014] In embodiments, R 1N teeth, [ka] is.

[0015] In embodiments, R 1N teeth, [ka] is.

[0016] In another aspect, the invention features a compound having a structure according to the following general formula (I″): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R aa and R bb are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl; R N1’ is hydrogen or C1-C7 alkyl, R AA are each independently a C1-C7 linear alkyl; R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; aa is 0, 1, or 2, and In the formula, R N1’ is hydrogen, then aa is 1 or 2.

[0017] In embodiments, R N1’ is a C1-C7 alkyl.

[0018] In embodiments, R aa and R bb are ethyl, respectively.

[0019] In an embodiment, aa is 0 or 1.

[0020] In embodiments, aa is 1 or 2 and R AA are each methyl.

[0021] In embodiments, a is 1 or 2.

[0022] In embodiments, R 2a are each independently a halogen.

[0023] In embodiments, R 2a are each independently -F or -Cl.

[0024] In embodiments, the C5 carbon of the 2-pyrrolidinone has the (R)-configuration.

[0025] In embodiments, the C5 carbon of the 2-pyrrolidinone has the (S)-configuration.

[0026] In another aspect, the invention features a compound having a structure according to the following general formula (I): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R a and R b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl, or R a and R b together with the atoms to which they are attached form a carbocylic ring having 3 to 7 ring atoms, optionally containing a double bond, or R a and R b together with the atoms to which they are attached, are O, S, SO, SO2 and NR 1 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R N1is C1-C7 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl; A 1 teeth, [ka] is selected from the group consisting of R 1 C6~C 10 an aryl, a five- or six-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R 3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, and R A is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; aa is 0, 1, or 2; m is 1, 2, or 3; and n is 1, 2, 3, or 4.

[0027] In embodiments of general formula (I), R a and R b together with the atoms to which they are attached form a ring with 6 to 8 ring atoms, one of which is O, S, SO, SO2, and NR 1 is a moiety selected from the group consisting of:

[0028] In embodiments of general formula (I), R a and R b are each methyl or ethyl, or R a and R b are joined to form an unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, or cycloalkyl.

[0029] In embodiments, the compound of general formula (I) has a structure according to general formula (IA): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N1 is an unsubstituted C1-C7 alkyl, and R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2.

[0030] In embodiments, the compound of general formula (I) has one of the following structures: [ka] .

[0031] In another aspect, the invention features a compound having a structure according to the following general formula (II): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N2 is hydrogen, C1-C7 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl; A 2 teeth, [ka] is selected from the group consisting of R 1 C6~C 10 an aryl, a five- or six-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R 3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, and R Ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; aa is 0, 1, or 2; m is 1, 2, or 3; and n is 1, 2, 3, or 4.

[0032] In embodiments, the compound of general formula (II) has a structure according to general formula (II-A): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, wherein R 2a is each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; and a is 0, 1, or 2.

[0033] In embodiments, the compound of general formula (II) has one of the following structures: [ka] .

[0034] In an embodiment of general formula (II), R N2 is hydrogen.

[0035] In embodiments of general formulas (I) and (II), R 2 is phenyl, naphthyl, pyridyl, indolyl and [ka] and R 3 is selected from the group consisting of phenyl, naphthyl, pyridyl and indolyl.

[0036] In embodiments of general formulas (I) and (II), R 2 is phenyl substituted with 0 to 3 substituents, or [ka] where R 2 is phenyl substituted with 0 to 3 substituents.

[0037] In embodiments of general formulas (I) and (II), R 1 are imidazoles, oxazoles, isoxazoles, [ka] wherein: R 4a , R 4b , R 4c , R 6a , R 6b , and R 6c are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, or R 6a and R 6boptionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, and R 4d and R 6d are each selected from the group consisting of phenyl, benzyl, pyridyl, —CH2(pyridyl), imidazole, and —CH2(imidazole); R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; y 1 is 0, 1, or 2, and y 2 is 0, 1, or 2.

[0038] In embodiments of general formulas (I) and (II), R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] In embodiments, R N2 If is hydrogen, then y 1 is 1 or 2, and R 5 is not a C1-C7 unsubstituted alkyl or a C3-C7 unsubstituted cycloalkyl.

[0039] In embodiments of general formulas (I) and (II), R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C6-C 10 aryl, 5- to 10-membered heteroaryl, and 1 is 0. In an embodiment, R N2 is hydrogen, R 5 is not a C1-C7 unsubstituted alkyl or a C3-C7 unsubstituted cycloalkyl.

[0040] In embodiments of general formulas (I) and (II), C1-C7 haloalkyl or C3-C7 cyclohaloalkyl is C1-C7 fluoroalkyl or C3-C7 cyclofluoroalkyl.

[0041] In embodiments of general formulas (I) and (II), the 5- to 10-membered heteroaryl is selected from the group consisting of tetrazole, pyridyl, and pyridazine.

[0042] In embodiments of general formulas (I) and (II), R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , and NHCONR 8f In embodiments, R N If is hydrogen, then y 1 is 1 or 2, and R 7 is not a C1-C7 unsubstituted alkyl or a C3-C7 unsubstituted cycloalkyl.

[0043] In embodiments of general formula (I) and general formula (II), R 1 teeth, COOR 5 , where R 5 C6~C 10 aryl or 5- to 10-membered heteroaryl; [ka] In the formula, R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8his unsubstituted C1-C7 alkyl, [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8a and R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is unsubstituted C1-C7 alkyl, [ka] In the formula, R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8aand R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h are independently unsubstituted C1-C7 alkyl; or [ka] is.

[0044] In another aspect, the invention features a compound having a structure according to the following general formula (III): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R a and R b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl, or R a and R b together with the atoms to which they are attached form a ring having 5 to 7 ring atoms, optionally containing a double bond, or R a and R b together with the atoms to which they are attached, are O, S, SO, SO2 and NR 1 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R N3 is hydrogen, C1-C7 alkyl, C6-C 10 heteroaryl or 5- to 10-membered heteroaryl; A 3is an N-linked, 5- to 12-membered nitrogen-containing heterocyclyl, which may be monocyclic, bicyclic, or polycyclic and optionally contain additional heteroatoms selected from O, N, and S, and non-aromatic nitrogen-containing heterocyclyls are represented by R 2 further comprising a group, R 1 is H, C1-C7 alkyl, C3-C7 cycloalkyl, phenyl, benzyl, a 5- to 6-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R 3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, m is 1, 2, or 3, and n is 1, 2, 3, or 4, and In the formula, R N3 If is hydrogen, A 3 teeth, [ka] Instead, in the formula, R A is phenyl, (CH2) 1~3 -(phenyl), naphthyl, (CH2) 1~3 -(naptyl), pyridyl, or (CH2) 1~3 -(pyridyl) group.

[0045] In an embodiment of general formula (III), R a and R b together with the atoms to which they are attached form a ring having 6 to 8 ring atoms, one of which is O, S, SO, SO2, and NR 1 is a moiety selected from the group consisting of:

[0046] In embodiments, the compound of general formula (III) has one of the following structures: [ka] .

[0047] In embodiments, the compound of general formula (III) has one of the following structures: [ka] .

[0048] In embodiments, the compound of general formula (III) has one of the following structures: [ka] .

[0049] In embodiments, the compound has the following structure: [ka] It has one of the following.

[0050] In an embodiment of general formula (III), R N3 is hydrogen.

[0051] In an embodiment of general formula (III), R N3 is a C1-C7 alkyl.

[0052] In an embodiment of general formula (III), R a and R b are each methyl or ethyl, or R a and R b are joined to form an unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0053] In the embodiment of general formula (III), A 3 is selected from the group consisting of: [ka] R 2 is phenyl, naphthyl, pyridyl, indolyl, and [ka] is selected from the group consisting of R 3 is selected from the group consisting of phenyl, naphthyl, pyridyl, and indolyl; R A is C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C 1~ C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C 1~ C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl and five- to six-membered heterocyclic groups each containing from one to four heteroatoms selected from oxygen, sulfur, and nitrogen; and aa is independently 0, 1, or 2.

[0054] In an embodiment of general formula (III), aa is 0.

[0055] In an embodiment of general formula (III), aa is 1.

[0056] In an embodiment of general formula (III), aa is 2.

[0057] In the embodiment of general formula (III), A 3 teeth, [ka] wherein A is selected from the group consisting of 3 teeth [ka] No.

[0058] In an embodiment of general formula (III), R 1 is H, C1-C7 alkyl, C3-C7 cycloalkyl, phenyl, benzyl, imidazole, oxazole, [ka] is selected from the group consisting of R 4a , R 4b , R 4c , R 6a , R 6b , and R 6c are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 6a and R 6b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 4d and R 6d are each selected from the group consisting of phenyl, benzyl, pyridyl, —CH2(pyridyl), imidazole, and —CH2(imidazole); R 5is hydrogen, C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 7 is hydrogen, C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , and R 8g are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R8h are each C1-C7 alkyl or C3-C7 cycloalkyl, or R 4a and R 8g when both are present, optionally taken together with the atoms to which they are attached to form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl. Selected, R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; y 1 is 0, 1, or 2, and y 2 is 0, 1, or 2.

[0059] In an embodiment of general formula (III), R 1 is selected from the group consisting of: [ka] .

[0060] In an embodiment of general formula (III), R 1 is: COOR 5 , where R 5 C6~C 10 aryl or 5- to 10-membered heteroaryl; [ka] In the formula, R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; [ka] In the formula, R 8a and R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is unsubstituted C1-C7 alkyl, [ka] In the formula, R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is unsubstituted C1-C7 alkyl, [ka] In the formula, R 8a and R 8b are each independently H or unsubstituted C1-C7 alkyl; [ka] In the formula, R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h are independently unsubstituted C1-C7 alkyl; or [ka] .

[0061] In embodiments, the compound of general formula (I), (I'), (I''), (II), or (III) is any one of compounds A1-A209, including enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof.

[0062] In embodiments, the compound is selected from the group consisting of: [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0063] In embodiments, the compound is selected from the group consisting of: [ka] [ka] [ka] [ka]

[0064] In another aspect, the invention features a pharmaceutical composition including any compound described herein (e.g., a compound according to any one of general formulas (I), (I'), (I''), (II), or (III)), or a pharmaceutically acceptable salt thereof. In embodiments, the pharmaceutical composition further includes at least one pharmaceutically acceptable excipient.

[0065] In another aspect, the invention features a method for treating a disease associated with dysregulated activity of 5-hydroxytryptamine receptor 7, the method including administering to a subject an effective amount of at least one compound described herein (e.g., a compound according to any one of general formulas (I), (I'), (I''), (II), or (III)) or a pharmaceutically acceptable salt thereof.

[0066] In embodiments, at least one compound (e.g., a compound according to any one of general formulas (I), (I'), (I''), (II), or (III)), or a pharmaceutically acceptable salt thereof, is administered in a composition further comprising at least one excipient.

[0067] In embodiments, the disease associated with dysregulated 5-hydroxytryptamine receptor 7 activity is selected from the group consisting of a peripherally selective disease, a nervous system disease, a circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disorders, memory disorders, hippocampal signaling disorders, sleep disorders, attention deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphonic disorder, seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcohol addiction, breast cancer, liver fibrosis, chronic liver disorders, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury.

[0068] In embodiments, the disease associated with dysregulated activity of 5-hydroxytryptamine receptor 7 is inflammatory bowel disease (IBD) or enterocolitis. DETAILED DESCRIPTION OF THE INVENTION

[0069] 6. Detailed Description of Methods 6.1 Definition Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used to practice or test the present invention, exemplary methods, devices and materials are now described. All technical and patent literature cited herein is incorporated herein by reference in its entirety. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention.

[0070] Throughout this specification, when a composition is described as having, containing, or comprising particular ingredients, or a method is described as having, containing, or comprising particular method steps, it is intended that the compositions of the present teachings consist essentially of or consist of the recited ingredients, and that the methods of the present teachings also consist essentially of or consist of the recited method steps.

[0071] Throughout this application, when an element or component is described as being included in and / or selected from a recited list of elements or components, it is understood that the element or component may be any one of the recited elements or components, or may be selected from a group consisting of two or more of the recited elements or components.

[0072] As used herein, the use of the singular includes the plural (and vice versa) unless otherwise specified. Furthermore, when the term "about" is used before a quantitative value, the present teachings also include the particular quantitative value itself, unless otherwise specified.

[0073] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present teachings remain operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0074] As used herein, the term "halogen" is meant to mean chlorine, bromine, fluorine, and iodine.

[0075] As used herein, unless otherwise specified, "alkyl" and / or "aliphatic," whether used alone or as part of a substituent, refer to straight and branched carbon chains having 1 to 20 carbon atoms, or any number within this range, e.g., 1 to 6 carbon atoms or 1 to 4 carbon atoms. A specified number of carbon atoms (e.g., C1-C6) refers independently to the number of carbon atoms within the alkyl moiety or the alkyl portion of a larger alkyl-containing substituent. Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, and the like. Alkyl groups can be unsubstituted or substituted, including with any of the substituents and combinations of substituents described herein. Non-limiting examples of substituted alkyl groups include hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, 3-carboxypropyl, and the like. In substituents having multiple alkyl groups, such as (C1-C6 alkyl)2amino, the alkyl groups can be the same or different.

[0076] As used herein, the terms "alkenyl" and "alkynyl" groups, whether used alone or as part of a substituent group, refer to straight and branched carbon chains having two or more carbon atoms, preferably from 2 to 20 carbon atoms, and an alkenyl chain is one in which the carbon atoms in the chain are bonded together. The alkynyl group has at least one double bond in the chain, and the alkynyl chain has at least one triple bond in the chain. Alkenyl and alkynyl groups can be unsubstituted or substituted. Non-limiting examples of alkenyl groups include ethenyl, 3-propenyl, 1-propenyl (also known as 2-methylethenyl), isopropenyl (also known as 2-methylethen-2-yl), buten-4-yl, and the like. Non-limiting examples of substituted alkenyl groups include 2-chloroethenyl (also known as 2-chlorovinyl), 4-hydroxybuten-1-yl, 7-hydroxy-7-methyloct-4-en-2-yl, 7-hydroxy-7-methyloct-3,5-dien-2-yl, and the like. Non-limiting examples of alkynyl groups include ethynyl, prop-2-ynyl (also known as propargyl), propyn-1-yl, and 2-methyl-hex-4-yn-1-yl. Non-limiting examples of substituted alkynyl groups include 5-hydroxy-5-methylhex-3-ynyl, 6-hydroxy-6-methylhept-3-yn-2-yl, 5-hydroxy-5-ethylhept-3-ynyl, and the like.

[0077] As used herein, "cycloalkyl," whether used alone or as part of another group, refers to a non-aromatic carbon-containing ring, including cyclized alkyl, alkenyl, and alkynyl groups, for example, having 3 to 14 ring carbon atoms, preferably 3 to 7 or 3 to 6 ring carbon atoms, or 3 to 4 ring carbon atoms, and optionally containing one or more (e.g., 1, 2, or 3) double or triple bonds. Cycloalkyl groups can be monocyclic (e.g., cyclohexyl) or polycyclic (e.g., containing fused, bridged, and / or spiro ring structures), with the carbon atoms located inside or outside the ring structure. Any suitable ring position of a cycloalkyl group can be covalently linked to the defined chemical structure. Cycloalkyl rings can be unsubstituted or substituted. Non-limiting examples of cycloalkyl groups include cyclopropyl, 2-methyl-cyclopropyl, cyclopropenyl, cyclobutyl, 2,3-dihydroxycyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctanyl, decalinyl, 2,5-dimethylcyclopentyl, 3,5-dichlorocyclohexyl, 4-hydroxycyclohexyl, 3,3,5-trimethylcyclohex-1-yl, octahydropentalenyl, octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden-4-yl, decahydroazulenyl, bicyclo[6.2.0]decanyl, decahydronaphthalenyl, and dodecahydro-1H-fluorenyl. The term "cycloalkyl" also includes carbocyclic rings that are bicyclic hydrocarbon rings, non-limiting examples of which include bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, 1,3-dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl.

[0078] "Haloalkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms substituted with one or more halogens. Haloalkyl groups include perhaloalkyl groups in which all hydrogen atoms on the alkyl group have been replaced with halogens (e.g., -CF3, -CF2CF3). Haloalkyl groups can optionally be substituted with one or more substituents in addition to halogens. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, dichloroethyl, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl groups.

[0079] The term "alkoxy" refers to the group -O-alkyl, where alkyl is as defined above. The alkoxy group may be optionally substituted. The term C3-C6 cyclic alkoxy refers to a ring containing 3-6 carbon atoms and at least one oxygen atom (e.g., tetrahydrofuran, tetrahydro-2H-pyran). The C3-C6 cyclic alkoxy group may be optionally substituted.

[0080] The term "haloalkoxy" means an -O-haloalkyl group, where haloalkyl is as defined above. Examples of haloalkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, and pentafluoroethoxyl.

[0081] The term "aryl," used alone or as part of another group, is defined herein as a 6-membered, unsaturated, aromatic monocyclic ring or a 6- to 14-membered, unsaturated, aromatic polycyclic ring. Aryl groups can be unsubstituted or substituted. Aryl rings can be, for example, phenyl or naphthyl rings, each optionally substituted with one or more moieties capable of replacing one or more hydrogen atoms. Non-limiting examples of aryl groups include phenyl, naphthylene-1-yl, naphthylene-2-yl, 4-fluorophenyl, 2-hydroxyphenyl, 3-methylphenyl, 2-amino-4-fluorophenyl, 2-(N,N-diethylamino)phenyl, 2-cyanophenyl, 2,6-di-tert-butylphenyl, 3-methoxyphenyl, 8-hydroxynaphthylene-2-yl, 4,5-dimethoxynaphthylene-1-yl, and 6-cyano-naphthylene-1-yl. Aryl groups also include, for example, phenyl or naphthyl rings fused with one or more saturated or partially saturated carbocyclic rings (e.g., bicyclo[4.2.0]octa-1,3,5-trienyl, indanyl) in which one or more carbon atoms of the aromatic ring and / or the saturated or partially saturated ring may be substituted.

[0082] The term "arylalkyl" or "aralkyl" refers to the group -alkyl-aryl, where the alkyl and aryl groups are as defined herein. The aralkyl groups of the present invention are optionally substituted. Examples of arylalkyl groups include, for example, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 2-phenylpropyl, fluorenylmethyl, and the like.

[0083] The terms "heterocyclic" and / or "heterocycle" and / or "heterocylyl," used alone or as part of another group, are defined as one or more rings having 3 to 20 atoms, wherein at least one atom in at least one ring is a heteroatom selected from nitrogen (N), oxygen (O), or sulfur (S), and wherein the heteroatom-containing ring(s) is / are non-aromatic. In heterocyclic groups containing two or more fused rings, the non-heteroatom-containing ring(s) may be aryl (e.g., indolinyl, tetrahydroquinolinyl, chromanyl). Exemplary heterocyclic groups have 3 to 14 ring atoms, 1 to 5 of which are independently heteroatoms selected from nitrogen (N), oxygen (O), or sulfur (S). One or more N or S atoms in a heterocyclic group can be oxidized. A heterocyclic group can be unsubstituted or substituted.

[0084] Non-limiting examples of heterocyclic units having a single ring include diazirinyl, aziridinyl, urazolyl, azetidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolidinyl, isothiazolyl, isothiazolinyl, oxathiazolidinonyl, oxazolidinonyl, hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl, piperidinyl, dihydropyranyl, tetrahydropyranyl, piperidin-2-onyl (valerolactam), 2,3,4,5-tetrahydro-1H-azepinyl, 2,3-dihydro-1H-indole, and 1,2,3,4-tetrahydro-quinoline. Non-limiting examples of heterocyclic units having two or more rings include hexahydro-1H-pyrrolidinyl, 3a,4,5,6,7,7a-hexahydro-1H-benzo[d]imidazolyl, 3a,4,5,6,7,7a-hexahydro-1H-indolyl, 1,2,3,4-tetrahydroquinolinyl, chromanyl, isochromanyl, indolinyl, and isoindolyl. dolinyl, and decahydro-1H-cycloocta[b]pyrrolyl.

[0085] The term "heteroaryl," whether used alone or as part of another group, is defined herein as one or more rings having 5 to 20 atoms, wherein at least one atom in at least one ring is a heteroatom selected from nitrogen (N), oxygen (O), or sulfur (S), and wherein at least one of the heteroatom-containing rings is aromatic. In heteroaryl groups containing two or more fused rings, the non-heteroatom-containing ring may be carbocyclic (e.g., 6,7-dihydro-5H-cyclopentapyrimidine) or aryl (e.g., benzofuranyl, benzothiophenyl, indolyl). Exemplary heteroaryl groups have 5 to 14 ring atoms and contain 1 to 5 ring heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). One or more N or S atoms in a heteroaryl group can be oxidized. Heteroaryl groups can be unsubstituted or substituted. Non-limiting examples of heteroaryl rings containing a single ring include 1,2,3,4-tetrazolyl, [1,2,3]triazolyl, [1,2,4]triazolyl, triazinyl, thiazolyl, 1H-imidazolyl, oxazolyl, furanyl, thiopheneyl, pyrimidinyl, 2-phenylpyrimidinyl, pyridinyl, 3-methylpyridinyl, and 4-dimethylaminopyridinyl. Non-limiting examples of heteroaryl rings containing two or more fused rings include benzofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, cinnolinyl, naphthyridinyl, phenanthridinyl, 7H-purinyl, 9H-purinyl, 6-amino-9H-purinyl, 5H-pyrrolo[3,2-d]pyrimidinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, pyr ... do[2,3-d]pyrimidinyl, 2-phenylbenzo[d]thiazolyl, 1H-indolyl, 4,5,6,7-tetrahydro-1-H-indolyl, quinoxalinyl, 5-methylquinoxalinyl, quinazolinyl, quinolinyl, 8-hydroxy-quinolinyl, 1H-benzo-[d]imidazol-2(3H)-onyl, 1H-benzo[d]imidazolyl, and isoquinolinyl.

[0086] One non-limiting example of the heteroaryl group described above is C1-C5 heteroaryl, which has 1 to 5 carbon ring atoms and at least one additional ring atom that is a heteroatom independently selected from nitrogen (N), oxygen (O), or sulfur (S) (preferably 1 to 4 additional ring atoms that are heteroatoms). Examples of C1-C5 heteroaryl include, but are not limited to, triazinyl, thiazol-2-yl, thiazol-4-yl, imidazol-1-yl, 1H-imidazol-2-yl, 1H-imidazol-4-yl, isoxazolin-5-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl.

[0087] Unless otherwise specified, two substituents taken together form a ring having a specified number of ring atoms (e.g., R 2 and R 3 together with their attached nitrogen (N) form a ring having 3 to 7 ring members, the ring can have carbon atoms and, optionally, one or more (e.g., 1 to 3) additional heteroatoms independently selected from nitrogen (N), oxygen (O), or sulfur (S). The ring can be saturated or partially saturated and optionally substituted.

[0088] For the purposes of the present invention, fused ring units as well as spirocyclic rings, bicyclic rings, and the like, containing a single heteroatom are considered to belong to the ring family corresponding to heteroatom-containing rings. For example, 1,2,3,4-tetrahydroquinoline, having the general formula: [ka] In the present invention, 6,7-dihydro-5H-cyclopentapyrimidine, which has the general formula: [ka] In the present invention, it is considered as a heteroaryl unit. When a fused ring unit contains heteroatoms in both the saturated ring and the aryl ring, the aryl ring is dominant and determines the classification of the ring species to which it is assigned. For example, 1,2,3,4-tetrahydro-[1,8]naphthyridine having the following general formula: [ka] In the present invention, it is considered a heteroaryl unit.

[0089] Whenever a term or any of its prefix roots appears in the name of a substituent, that name should be interpreted as including the limitations provided herein. For example, when the term "alkyl" or "aryl" or any of its prefix roots appears in the name of a substituent (e.g., arylalkyl, alkylamino), that name should always be interpreted as including the limitations set forth above for "alkyl" and "aryl."

[0090] The term "substituted" is used throughout this specification. The term "substituted" is defined herein as a moiety, whether acyclic or cyclic, having one or more hydrogen atoms substituted with a substituent or several (e.g., 1 to 10) substituents as defined herein below. The substituents can replace one or two hydrogen atoms of a single moiety at a time. Furthermore, these substituents can replace two hydrogen atoms attached to two adjacent carbons to form the substituent, i.e., a new moiety or unit. For example, substituted units requiring the replacement of a single hydrogen atom include halogen, hydroxyl, etc. Replacements of two hydrogen atoms include carbonyl, oximino, etc. Replacements of two hydrogen atoms on adjacent carbon atoms include epoxy, etc. The term "substituted" is used throughout this specification to indicate that a moiety can have one or more hydrogen atoms replaced by a substituent. When a moiety is described as "substituted," any number of hydrogen atoms may be replaced. For example, difluoromethyl is a substituted C1 alkyl, trifluoromethyl is a substituted C1 alkyl, 4-hydroxyphenyl is a substituted aromatic ring, (N,N-dimethyl-5-amino)octanyl is a substituted C8 alkyl, 3-guanidinopropyl is a substituted C3 alkyl, and 2-carboxypyridinyl is a substituted heteroaryl.

[0091] Variable groups defined herein, such as alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, aryloxy, aryl, heterocyclic, and heteroaryl groups defined herein, whether used alone or as part of another group, can be optionally substituted. Optionally substituted groups are also designated.

[0092] The following are non-limiting examples of substituents that can replace a hydrogen atom of a moiety: halogen (chlorine (Cl), bromine (Br), fluorine (F), and iodine (I)), -CN, -NO2, oxo (=O), -OR', -SR', -N(R')2, -NR'C(O)R' , -SO2R', -SO2OR', -SON(R')2, -C(O)R', -C(O)OR', -C(O)N(R')2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C2-C8 alkenyl, C2-C8 alkynyl, C3-C 14 cycloalkyl, aryl, heterocycle, or heteroaryl, wherein each of the alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocycle, and heteroaryl groups is optionally substituted with 1 to 10 (e.g., 1 to 6 or 1 to 4) groups independently selected from halogen, —CN, —NO2, oxo, and R′, wherein R′ at each occurrence is independently selected from hydrogen, —OR″, —SR″, —C(O)R″, —C(O)OR″, —C(O)N(R″)2, —S02R″, —S(O)2OR″, —N(R″)2, —NR″C(O)R″, C1-C6 alkyl, C1-C6 haloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, cycloalkyl (e.g., or two R' units together with the atom to which they are attached form an optionally substituted carbocyclic or heterocyclic ring having 3 to 7 ring atoms, wherein R" at each occurrence is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, cycloalkyl (e.g., C3-C6 cycloalkyl), aryl, heterocyclic or heteroaryl; or two R" units together with the atom to which they are attached form an optionally substituted carbocyclic or heterocyclic ring having 3 to 7 ring atoms, preferably

[0093] In some embodiments, the substituent is i) -OR'''; for example, -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3; ii)-C(O)R'''; For example, -COCH3, -COCH2CH3, -COCH2CH2CH3; iii) -C(O)OR'''; for example, -CO2CH3, -CO2CH2CH3, -CO2CH2CH2CH3; iv) -C(O)N(R''')2; e.g., -CONH2, -CONHCH3, -CON(CH3)2; v) -N(R''')2; for example, -NH2, -NHCH3, -N(CH3)2, -NH(CH2CH3); vi) halogens: -F, -Cl, -Br, and -I; vii)-CH e X g wherein X is a halogen, m is 0 to 2, and e+g=3; for example, -CH2F, -CHF2, -CF3, -CCl3, or -CBr3; viii) -SO2R'''; e.g., -SO2H; -SO2CH3; -SO2C6H5; ix) C1-C6 linear, branched, or cyclic alkyl; x) cyano; xi) nitro; xii)N(R''')C(O)R''; xiii) oxo(=O); xiv) heterocycles; and xv) heteroaryl; wherein each R'"' is independently hydrogen, an optionally substituted C1-C6 straight or branched alkyl (e.g., an optionally substituted C1-C4 straight or branched alkyl), or an optionally substituted C3-C6 cycloalkyl (e.g., an optionally substituted C3-C4 cycloalkyl), or two R'"' units can be joined to form a ring containing 3 to 7 ring atoms. In certain embodiments, , each R''' is independently hydrogen, C1-C6 straight or branched alkyl optionally substituted with halogen or C3-C6 cycloalkyl, or C3-C6 cycloalkyl.

[0094] At various places in the present specification, substituents of compounds are disclosed in groups or in ranges. It is specifically intended that the description also include individual subsets of such group members and ranges. For example, "C 1~6 The term "alkyl" is specifically intended to independently disclose C1, C2, C3, C4, C5, C6, C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6 alkyl.

[0095] As used herein, the terms "compound," "analog," and "composition of matter" equally adequately refer to the 5-hydroxytryptamine receptor 7 modulators described herein, including all enantiomeric forms, diastereomeric forms, salts, etc., and the terms "compound," "analog," and "composition of matter" are used interchangeably throughout this specification.

[0096] The compounds described herein may contain asymmetric atoms (also called chiral centers), and some compounds may contain one or more asymmetric atoms or centers, which can give rise to optical isomers (enantiomers) and diastereomers. The teachings and compounds disclosed herein include such enantiomers and diastereomers, as well as racemic, resolved, enantiomerically pure R and S stereoisomers, and other mixtures of R and S stereoisomers and pharmaceutically acceptable salts thereof. For example, described herein are certain pyrrolidinones containing a substituent at the C5 carbon of the heterocycle. In any compound or general formula embodiment described herein, the C5 carbon has the (S)-configuration. In any compound or general formula embodiment described herein, the C5 carbon has the (R)-configuration. Optical isomers can be obtained in pure form by standard procedures known to those skilled in the art, including, but not limited to, diastereomeric salt formation, kinetic resolution, and asymmetric synthesis. The present teachings also encompass cis- and trans-isomers of compounds containing alkenyl moieties (e.g., alkenes and imines), and it is understood that the present teachings encompass all possible positional isomers, as well as mixtures thereof, which can be obtained in pure form by standard separation procedures known to those skilled in the art, including, but not limited to, column chromatography, thin-layer chromatography, and high-performance liquid chromatography.

[0097] Pharmaceutically acceptable salts of the compounds of the present teachings, which may have an acidic moiety, can be formed using organic and inorganic bases. Depending on the number of acidic hydrogens available for deprotonation, both monoanionic and polyanionic salts are considered. Suitable salts formed with bases include metal salts, such as alkali metal salts or alkaline earth metal salts, for example, sodium salts, potassium salts, or magnesium salts; ammonia salts and organic amine salts, such as salts formed with morpholine, thiomorpholine, piperidine, pyrrolidine, mono-, di-, or tri-lower alkylamines (e.g., ethyl-tert-butylamine, diethylamine, diisopropylamine, triethylamine, or dimethylpropylamine), or mono-, di-, or tri-hydroxy-lower alkylamines (e.g., monoethanolamine, diethanolamine, or triethanolamine). Specific non-limiting examples of inorganic bases include NaHCO3, Na2CO3, KHCO3, K2CO3, Cs2CO3, LiOH, NaOH, KOH, NaH2PO4, Na2HPO4, and Na3PO4. Inner salts can also be formed. When the compounds disclosed herein contain a basic moiety, salts can be formed using organic and inorganic acids. For example, salts can be formed with the following acids: acetic acid, propionic acid, lactic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, tartaric acid, succinic acid, dichloroacetic acid, ethenesulfonic acid, formic acid, fumaric acid, gluconic acid, glutamic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, mucic acid, napthalenesulfonic acid, nitric acid, oxalic acid, pamoic acid, pantothenic acid, phosphoric acid, phthalic acid, propionic acid, succinic acid, sulfuric acid, tartaric acid, toluenesulfonic acid, and camphorsulfonic acid, as well as other known pharmaceutically acceptable acids.

[0098] When any variable occurs more than one time in any constituent or in any general formula, its definition on each occurrence is independent of its definition at every other occurrence (e.g., N(R 9 )2, R 9 (each may be the same or different from the other). Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0099] As used herein, the terms "treat" and "treating" and "treatment" mean to partially or completely alleviate, suppress, improve, and / or relieve a condition from which a patient is suspected to suffer.

[0100] As used herein, "therapeutically effective" and "effective dose" refer to a substance or amount that elicits a desired biological activity or effect.

[0101] Except where noted, the terms "subject" or "patient" are used interchangeably and refer to mammals, such as human patients and non-human primates, as well as laboratory and other animals, such as rabbits, rats, and mice. Thus, as used herein, the term "subject" or "patient" refers to any mammalian patient or subject to which a compound of the present invention can be administered. In exemplary embodiments of the present invention, to identify target patients for treatment with the methods of the present invention, recognized screening methods are used to measure risk factors associated with the targeted or suspected disease or condition, or to measure the subject's existing disease or condition status. These screening methods include, for example, conventional workups to measure risk factors that may be associated with the targeted or suspected disease or condition. These and other routine methods allow clinicians to select patients in need of treatment using the methods and compounds of the present invention. 6.2 Modulators of 5-hydroxytryptamine receptor 7 activity Regulators of 5-HT7 activity

[0102] Described herein are compounds capable of modulating 5-hydroxyreceptor 7 (5-HT7) activity. In particular, the compounds described herein can be selective modulators of the 5-HT7 receptor. In embodiments, selective modulation of 5-HT7 includes selectively modulating 5-HT7 relative to other receptors. In embodiments, selective modulation of 5-HT7 includes, for example, selectively modulating 5-HT7 expressed in specific organs and tissues. Thus, the compounds described herein can be useful in treating various diseases and conditions (e.g., as described herein).

[0103] In embodiments of any of the general formulas described herein, the C1-C7 alkyl is a C1-C7 straight chain alkyl. In embodiments, the C1-C7 alkyl is an unsubstituted C1-C7 straight chain alkyl. In embodiments, the C1-C7 alkyl is a substituted C1-C7 straight chain alkyl (e.g., substituted with one, two, three, or more substituents described herein). In embodiments, the substituted C1-C7 straight chain alkyl is a C1-C7 straight chain perhalogenated alkyl. In an embodiment, the substituted C1-C7 linear alkyl is OH, OCH3, NH 2、 CN, CH 3、 CF 3、 and includes 1, 2, or 3 substituents selected from the group consisting of CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of C1-C7 alkyl are described herein.

[0104] In embodiments of any of the general formulas described herein, the C1-C7 alkyl is a C3-C7 branched alkyl. In embodiments, the branched C3-C7 is an unsubstituted C3-C7 branched alkyl. In embodiments, the C3-C7 branched alkyl is a substituted C3-C7 branched alkyl (e.g., substituted with one, two, three, or more substituents described herein). In embodiments, the substituted C3-C7 branched alkyl is a C3-C7 branched perhaloalkyl (e.g., perfluoroalkyl ...), such as OH, OCH3, NH 2、 CN, CH 3、 CF 3、 and includes 1, 2, or 3 substituents selected from the group consisting of CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of C3-C7 branched alkyls are described herein.

[0105] In embodiments of any of the general formulas described herein, cycloalkyl is C3-C7 or C3-C8 cycloalkyl. In embodiments, cycloalkyl is cyclopropyl. In embodiments, cycloalkyl is cyclobutyl. In embodiments, cycloalkyl is cyclopentyl. In embodiments, cycloalkyl is cyclohexyl. In embodiments, cycloalkyl is unsubstituted cycloalkyl (e.g., unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl). In embodiments, cycloalkyl is substituted cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl containing 1, 2, 3, 4, or 5 substituents, including exemplary substituents described herein). In embodiments, substituted cycloalkyl contains 1, 2, or 3 substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of cycloalkyl are described herein.

[0106] In any of the general formula embodiments described herein, C6-C 10 Aryl is phenyl. In embodiments, the phenyl is unsubstituted phenyl. In embodiments, the phenyl is substituted phenyl (e.g., phenyl containing 1, 2, 3, 4, or 5 substituents, including exemplary substituents described herein). Substituted phenyl groups can be bonded through any available carbon of the ring, including those described herein. For example, phenyl can have a substituent described herein (e.g., OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2) in the para position relative to the point of attachment to a molecule (e.g., a 4-substituted phenyl group). In embodiments, phenyl can have a substituent described herein (e.g., OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2) in the meta position relative to the point of attachment to a molecule (e.g., a 3-substituted phenyl group). In embodiments, the phenyl can have a substituent described herein (e.g., OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH) at the ortho position relative to the point of attachment to a molecule (disubstituted phenyl group). The phenyl group can have two or more substituents (e.g., 2,3-disubstituted, 2,4-disubstituted, 2,5-disubstituted, 2,6-disubstituted, 3,4-disubstituted, or 3,5-disubstituted phenyl), or three or more substituents (e.g., 2,3,4-trisubstituted, 2,3,5-trisubstituted, 2,3,6-trisubstituted, 2,4,5-trisubstituted, 2 ... , 4,6-trisubstituted, 3,4,5-trisubstituted, or 3,4,6-trisubstituted). In embodiments, the substituted phenyl comprises one, two, or three substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of phenyl are described herein. In embodiments, phenyl is selected from unsubstituted phenyl, 4-OH-phenyl, 3-OH-phenyl, 2-OH-phenyl, 4-OMe-phenyl, 3-OMe-phenyl, 2-OMe-phenyl, 4-CN-phenyl, 3-CN-phenyl, 2-CN-phenyl, 4-Me-phenyl, 3-Me-phenyl, 2-Me-phenyl, 4-Et-phenyl, 3-Et-phenyl, 2-Et-phenyl, 4- i Pr-phenyl, 3- i Pr-phenyl, 2- i Pr-phenyl, 4-F-phenyl, 3-F-phenyl, 2-F-phenyl, 4-Cl-phenyl, 3-Cl-phenyl, 2-Cl-phenyl, 4-Br-phenyl, 3-Br-phenyl, 2-Br-phenyl, 4-NH2-phenyl, 3-NH2-phenyl, 2-NH2-phenyl, 4-CF3-phenyl, 3-CF3-phenyl, 2-CF3-phenyl, 2,3-di-Me-phenyl, 2,4-di-Me-phenyl, 2,5-di-Me-phenyl, 2,6-di-Me-phenyl, 4-morpholino-phenyl, 3-morpholino-phenyl, 2-morpholino-phenyl, 4-CN-2-morpholino-phenyl, 4-CH3-2-morpholino-phenyl, or 4-OH-2-morpholino-phenyl.

[0107] In any of the general formula embodiments described herein, C6-C 10Aryl is napthyl. In embodiments, napthyl is unsubstituted napthyl. In embodiments, napthyl is substituted napthyl (e.g., napthyl containing 1, 2, 3, 4, or 5 substituents, including exemplary substituents described herein). In embodiments, naphthyl is attached to the molecule at the C1-position (1-naphthyl). In embodiments, naphthyl is attached to the molecule at the C2-position (2-naphthyl). In embodiments, naphthyl is attached to the molecule at the C3-position (3-naphthyl). In embodiments, naphthyl is attached to the molecule at the C4-position (4-naphthyl). In embodiments, naphthyl is attached to the molecule at the C5-position (5-naphthyl). In embodiments, naphthyl is attached to the molecule at the C6-position (6-naphthyl). In embodiments, naphthyl is attached to the molecule at the C7-position (7-naphthyl). In embodiments, naphthyl is attached to the molecule at the C8-position (8-naphthyl). In embodiments, substituted naphthyl includes one, two, or three substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of napthyl are described herein.

[0108] In embodiments of any of the general formulae described herein, the 5- to 10-membered heteroaryl is imidazolyl. In embodiments, the imidazolyl is unsubstituted imidazolyl. In embodiments, the imidazolyl is substituted imidazolyl (e.g., imidazolyl containing 1, 2, or 3 substituents, including exemplary substituents described herein). In embodiments, the imidazolyl is an N-linked imidazolyl, attached to the molecule through the N1 position of the imidazolyl (1-imidazolyl). In embodiments, the imidazolyl is a C-linked imdazolyl. In embodiments, the imidazolyl is attached to the molecule through the C2 position of the imidazolyl group (2-imidazolyl). In embodiments, the imidazolyl is attached to the molecule through the C4 position of the imidazolyl group (4-imidazolyl). In embodiments, the imidazolyl is attached to the molecule through the C5 position of the imidazolyl group (5-imidazolyl). In embodiments, the substituted imidazolyl contains one, two, or three substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. In embodiments, the substituted imidazolyl is N-methylimidazolyl. The imidazolyl may also be Further exemplary embodiments are described herein.

[0109] In embodiments of any of the general formulae described herein, the 5- to 10-membered heteroaryl is pyrrolyl. In embodiments, the pyrrolyl is unsubstituted pyrrolyl. In embodiments, the pyrrolyl is an N-linked pyrrolyl, attached to the molecule through the N1 position of the pyrrolyl (1-pyrrolyl). In embodiments, the pyrrolyl is a C-linked pyrrolyl. In embodiments, the pyrrolyl is attached to the molecule through the C2 position of the pyrrolyl (2-pyrrolyl). In embodiments, the pyrrolyl is attached to the molecule through the C3 position of the pyrrolyl (3-pyrrolyl). In embodiments, the pyrrolyl is attached to the molecule through the C4 position of the pyrrolyl (4-pyrrolyl). In embodiments, the pyrrolyl is attached to the molecule through the C5 position of the pyrrolyl (5-pyrrolyl). In embodiments, the pyrrolyl is a substituted pyrrolyl (e.g., a pyrrolyl containing 1, 2, or 3 substituents, including exemplary substituents described herein). In embodiments, a substituted pyrrolyl includes one, two, or three substituents selected from the group consisting of OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. Still other exemplary embodiments of pyrrolyl are described herein.

[0110] In embodiments of any of the general formulas described herein, the 5- to 10-membered heteroaryl is oxazolyl. In embodiments, the oxazolyl is unsubstituted oxazolyl. In embodiments, the oxazolyl is attached to the molecule through the C2 position of the oxazolyl (2-oxazolyl). In embodiments, the oxazolyl is attached to the molecule through the C3 position of the oxazolyl (3-oxazolyl). In embodiments, the oxazolyl is attached to the molecule through the C4 position of the oxazolyl (4-oxazolyl). In embodiments, the oxazolyl is substituted oxazolyl (e.g., oxazolyl containing one or two substituents, including exemplary substituents described herein). In embodiments, the substituted oxazolyl contains one or two substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of imidazolyl are described herein.

[0111] In any of the general formula embodiments described herein, the 5- to 10-membered heteroaryl is tetrazolyl. In embodiments, the tetrazolyl is unsubstituted tetrazolyl. In embodiments, the tetrazolyl is substituted tetrazolyl (e.g., N-substituted tetrazolyl containing exemplary substituents described herein). Still other exemplary embodiments of tetrazolyl are described herein.

[0112] In embodiments of any of the general formulas described herein, the 5- to 10-membered heteroaryl is pyridyl. In embodiments, the pyridyl is unsubstituted pyridyl. In embodiments, the pyridyl is attached to the molecule through the C2 position (2-pyridyl). In embodiments, the pyridyl is attached to the molecule through the C3 position (3-pyridyl). In embodiments, the pyridyl is attached to the molecule through the C4 position (4-pyridyl). In embodiments, the pyridyl is attached to the molecule through the C2 position (5-pyridyl). In embodiments, the pyridyl is attached to the molecule through the C2 position (6-pyridyl). In embodiments, the pyridyl is substituted pyridyl (e.g., pyridyl containing 1, 2, 3, or 4 substituents, including exemplary substituents described herein). In embodiments, a substituted pyridyl includes one, two, or three substituents selected from the group consisting of OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. Still other exemplary embodiments of pyridyl are described herein.

[0113] In any of the general formula embodiments described herein, the 5- to 10-membered heteroaryl is , pyrazinyl. In embodiments, the pyrazinyl is unsubstituted pyrazinyl. In embodiments, the pyrazinyl is 2-pyrazinyl. In embodiments, the pyrazinyl is 3-pyrazinyl. In embodiments, the pyrazinyl is 5-pyrazinyl. In embodiments, the pyrazinyl is 6-pyrazinyl. In embodiments, the pyrazinyl is a substituted pyrazinyl (e.g., a pyrazinyl containing 1, 2, 3, or 4 substituents, including exemplary substituents described herein). In embodiments, the substituted pyrazinyl contains 1, 2, or 3 substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of pyrazinyl are described herein.

[0114] In embodiments of any of the general formulas described herein, the 5- to 10-membered heteroaryl is indolyl. In embodiments, the indolyl is unsubstituted indolyl. In embodiments, the indolyl is an N-linked indolyl, attached to a molecule through the N1 position of the indolyl (1-indolyl). In embodiments, the indolyl is a C-linked indolyl. In embodiments, the indolyl is attached to a molecule through the C2 position (2-indolyl). In embodiments, the indolyl is attached to a molecule through the C3 position (3-indolyl). In embodiments, the indolyl is attached to a molecule through the C4 position (4-indolyl). In embodiments, the indolyl is attached to a molecule through the C5 position (5-indolyl). In embodiments, the indolyl is attached to a molecule through the C6 position (6-indolyl). In embodiments, the indolyl is attached to a molecule through the C7 position (7-indolyl). In embodiments, the indolyl is a substituted indolyl (e.g., an indolyl containing one, two, three, or four substituents, including exemplary substituents described herein). In embodiments, the substituted indolyl contains one, two, or three substituents selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2. Still other exemplary embodiments of indolyl are described herein.

[0115] In any of the general formula embodiments described herein, the substituents can be C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C 1~C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 The substituents are selected from the group consisting of alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups, each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. In embodiments, the substituents themselves are unsubstituted. In embodiments, the substituents are selected from the group consisting of OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2.

[0116] In any of the general formula embodiments described herein, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration.

[0117] In any of the general formula embodiments described herein, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration.

[0118] In any of the general formula embodiments described herein, R A or R AA The carbon substituted with has the (R)-configuration.

[0119] In any of the general formula embodiments described herein, R A or R AA The carbon substituted with has the (S)-configuration.

[0120] General formula (I') and (I'' ) compounds Described herein are compounds of general formula (I'), as well as exemplary embodiments of general formula (I').

[0121] The exemplary general formulas and compounds described herein may also include hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0122] In one aspect, the invention features a compound having a structure according to the following general formula (I'): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N1’ is hydrogen or C1-C7 alkyl, R 1N are imidazoles, oxazoles, isoxazoles, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R.8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R AA are each independently a C1-C7 linear alkyl; R 2aare each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; aa is 0, 1, or 2, and y 1 is 0, 1, or 2.

[0123] In another aspect, the invention features a compound having a structure according to the following general formula (I'-N): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R N1’ is hydrogen or C1-C7 alkyl, R 1N-N C6~C 10 Heteroaryl, 5- to 10-membered heteroaryl, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R AA are each independently a C1-C7 linear alkyl; R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; aa is 0, 1, or 2, and y 1 is 0, 1, or 2.

[0124] In embodiments, R 5 is unsubstituted C1-C7 alkyl or unsubstituted C3-C7 cycloalkyl, and R N1’ is hydrogen, then aa is 1 or 2.

[0125] In embodiments, the compound according to general formula (I') has a structure according to the following general formula: [ka] In the formula, R 1N , R N1’ , R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0126] In embodiments, the compound according to general formula (I') has a structure according to the following general formula: [ka] In the formula, R 1N , R N1’ , R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0127] In embodiments, the compound according to general formula (I'-N) has a structure according to the following general formula: [ka] In the formula, R 1N-N , R N1’, R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0128] In embodiments, the compound according to general formula (I'-N) has a structure according to the following general formula: [ka] In the formula, R 1N-N , R N1’ , R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0129] In embodiments, R N1’ is hydrogen. In embodiments, R N1’ is C1-C7 alkyl. In an embodiment, R N1’ is methyl, ethyl, or isopropyl.

[0130] In embodiments, R AA are each independently a C1-C7 straight chain alkyl. AA Each is independently methyl.

[0131] In embodiments, aa is 0. In embodiments, aa is 1. In embodiments, aa is 2. In embodiments, aa is not 0. In embodiments, aa excludes 0. In embodiments, aa is 0 or 1. In embodiments, aa is 1 or 2.

[0132] In embodiments, R 2a Each is independently halogen. 2a are each independently F. In an embodiment, R 2a are each independently Cl.

[0133] In embodiments, a is 0. In embodiments, a is 1. In embodiments, a is 2. In embodiments, a is 1 or 2.

[0134] In embodiments, R 1N are imidazoles, oxazoles, isoxazoles, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, and y 1 is 0, 1, or 2.

[0135] In embodiments, R 1N-N C6~C 10 Heteroaryl, 5- to 10-membered heteroaryl, [ka] wherein: R 4a and R 4b are each hydrogen or C1-C7 alkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen; R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, and y 1 is 0, 1, or 2.

[0136] In embodiments, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] In embodiments, R 5 excludes unsubstituted C1-C7 alkyl. In embodiments, R 5 excludes unsubstituted C3-C7 cycloalkyl.

[0137] In embodiments, R 1N teeth, [ka] In an embodiment, R 1N-N teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0138] In embodiments, R1N teeth, [ka] In an embodiment, R 1N-N teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0139] In embodiments, R 1N-N teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0140] In an embodiment, y 1 is 0 and R 1 is COR 5 In an embodiment, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is a C3-C7 cyclofluoroalkyl.

[0141] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1is 2.

[0142] In embodiments, R 4a is H. In an embodiment, R 4b is H. In an embodiment, R 4a and R 4b are both H. In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0143] In embodiments, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is C3-C7 cyclofluoroalkyl. In an embodiment, R 5 is an unsubstituted C1-C7 alkyl. In embodiments, R 5 is a substituted C1-C7 alkyl (e.g., containing an amino substituent such as -NH2, -NHCH3, or -N(CH3)2). 5 is phenyl. In embodiments, R 5 is unsubstituted phenyl. In embodiments, R 5 is a substituted phenyl. In embodiments, R 5 is NR 8a R 8b In an embodiment, R 5 is SO2R 8c In an embodiment, R 5 is NR 8d SO2R 8e In an embodiment, R 5 is NR 8i COOR8j In an embodiment, R 5 NHCONR 8f In an embodiment, R 5 is NR 8g COR 8h In an embodiment, R 5 is not unsubstituted C1-C7 alkyl.

[0144] In embodiments, R 11 is hydrogen. In embodiments, R 11 is C1-C7 alkyl (e.g., methyl). In embodiments, R 11 is a C3-C7 cycloalkyl.

[0145] In embodiments, R 1N or R 1N-N teeth, [ka] wherein: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, Z a is CH2 or O, Z a If is CH2, p 1 +p 2 is 1, 2, 3, or 4, and Z a If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 Both are non-zero.

[0146] In embodiments, R 4a and R 4b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 4a and R 4b together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0147] In embodiments, R 1N or R 1N-N teeth [ka] wherein: Z b is CH2 or O, Z b If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z b If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , R 8i , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0148] In embodiments, R 1N or R 1N-N teeth, [ka] wherein: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, R 10a and R 10b are independently H, C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, SO2R 8e , COOR 8j ,CONR 8f , and C.O.R. 8h and R 10a and R 10b at least one of is selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8e , R 8f , and R 8h are each selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl.

[0149] In embodiments, R 1N-N is a urea group (e.g., [ka] is.

[0150] In embodiments, R 1N or R 1N-N is a carbamate group (e.g., [ka] ) In an embodiment, R 1N or R 1N-N is an aminoacyl group (e.g., [ka] ) In an embodiment, R 1N or R 1N-N is an alkyl acyl group (e.g., [ka] ) In an embodiment, R 1N or R 1N-N is aryl. In embodiments, R 1N or R 1N-N is a heteroaryl (e.g., [ka] ) In an embodiment, R 1N or R 1N-N is a heteroaryl containing an acyl group (e.g., [ka] ) is.

[0151] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl.

[0152] In embodiments, R 1N or R 1N-N teeth, [ka] where uu is 1 or 2.

[0153] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0154] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0155] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0156] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0157] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0158] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is an unsubstituted C1-C7 alkyl.

[0159] In embodiments, R 1N or R 1N-N teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0160] In embodiments, R1N or R 1N-N teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0161] In embodiments, R 1N or R 1N-N teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0162] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0163] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0164] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8his an unsubstituted C1-C7 alkyl.

[0165] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0166] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0167] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0168] In embodiments, R 1N or R 1N-N teeth [ka] where R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0169] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0170] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0171] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0172] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8a and R 8b are each independently H or an unsubstituted C1-C7 alkyl group. It's Rukiru.

[0173] In embodiments, R 1N or R 1N-N teeth, [ka] where R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h is independently unsubstituted C1-C7 alkyl.

[0174] In embodiments, R 1N or R 1N-N teeth, [ka] is.

[0175] In embodiments, R 1N or R 1N-N teeth, [ka] In an embodiment, R 1N or R 1N-N teeth, [ka] is.

[0176] In embodiments, the compound according to general formula (I') or (I'-N) has the following structure: [ka] In the formula, R N1’ , R 5 , R 4a , R 4b , R 2a , R AA , y 1 , aa, and a, respectively, according to any aspect or embodiment described herein.

[0177] In embodiments, the compound according to general formula (I') or (I'-N) has the following structure: [ka] In the formula, R N1’ , R 5 , R 4a , R 4b , R 2a , R AA , y 1 , aa, and a, respectively, according to any aspect or embodiment described herein.

[0178] In embodiments, the compound according to general formula (I'-N) has the following structure: [ka] In the formula, R N1’ , R 5 , R 11 , R 4a , R 4b , R 2a , RAA , y 1 , aa, and a, respectively, according to any aspect or embodiment described herein.

[0179] In embodiments, the compound according to general formula (I'-1), (I'-2), or (I'-3) has one of the following structures: [ka] During the ceremony, R N1’ , R 5 , R 11 , R 4a , R 4b , R 2a , R AA , y 1 , aa, and a are Each according to any aspect or embodiment described herein.

[0180] In another aspect, the invention features a compound having a structure according to the following general formula (I″): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R aa and R bb are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl; R N1’ is hydrogen or C1-C7 alkyl, R AA are each independently a C1-C7 linear alkyl; R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2; and aa is 0, 1, or 2.

[0181] In embodiments, R aa and R bb are each hydrogen or C1-C7 alkyl, and R N1’ is hydrogen, then aa is 1 or 2.

[0182] In embodiments, the compound according to general formula (I″) has a structure according to the following general formula: [ka] In the formula, R N1’ , R aa , R bb , R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0183] In embodiments, the compound according to general formula (I″) has a structure according to the following general formula: [ka] In the formula, R N1’ , R aa , R bb , R AA , R 2a , aa, and a according to any aspect or embodiment described herein.

[0184] In embodiments, R N1’ is hydrogen. In embodiments, R N1’ is C1-C7 alkyl. In an embodiment, R N1’ is methyl, ethyl, or isopropyl.

[0185] In embodiments, R AA are each independently a C1-C7 straight chain alkyl. AA Each is independently methyl.

[0186] In embodiments, aa is 0. In embodiments, aa is 1. In embodiments, aa is 2. In embodiments, aa is not 0. In embodiments, aa excludes 0. In embodiments, aa is 0 or 1. In embodiments, aa is 1 or 2.

[0187] In embodiments, R 2a Each is independently halogen. 2a are each independently F. In an embodiment, R 2a are each independently Cl.

[0188] In embodiments, a is 0. In embodiments, a is 1. In embodiments, a is 2. In embodiments, a is 1 or 2.

[0189] In embodiments, R aa is a C1-C7 straight chain alkyl. aa is a C3-C7 branched alkyl. In embodiments, R aa is ethyl. In embodiments, R bb is a C1-C7 straight chain alkyl. bb is a C3-C7 branched alkyl. In embodiments, R bb is ethyl. In embodiments, R aa and R bb are ethyl, respectively.

[0190] Compounds of general formula (I) Described herein are compounds of general formula (I), as well as exemplary embodiments of general formula (I).

[0191] The exemplary general formulas and compounds described herein may also include hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0192] In one aspect, the invention features a compound having a structure according to the following general formula (I): [ka] Enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof are included, wherein: R a and R b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl, or R a and R b together with the atoms to which they are attached form a carbocylic ring having 3 to 7 ring atoms, optionally containing a double bond, or R a and R b together with the atoms to which they are attached, are O, S, SO, SO2 and NR 1 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R N1 is C1-C7 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl; A 1 teeth, [ka] is selected from the group consisting of R 1 C6~C 10 an aryl, a five- or six-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R 3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, and R Ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; aa is 0, 1, or 2; m is 1, 2, or 3; and n is 1, 2, 3, or 4.

[0193] In embodiments, R a and R b together with the atoms to which they are attached form a ring having 6 to 8 ring atoms, one of which is O, S, SO, SO2, and NR 1 is a moiety selected from the group consisting of:

[0194] In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3. In embodiments, n is 4.

[0195] In embodiments, R N1 is C1-C7 alkyl. In an embodiment, R N1 is methyl, ethyl, or isopropyl.

[0196] In embodiments, R N1C6~C 10 In embodiments, R N1 is a 5- to 10-membered heteroaryl. In embodiments, the aryl or heteroaryl is unsubstituted. In embodiments, the aryl or heteroaryl may be the same or different and may be selected from C1 to C7 straight chain alkyl, C3 to C7 branched alkyl, C3 to C7 cycloalkyl, C 1~ C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, aryl In an embodiment, R is substituted with one or more substituents selected from the group consisting of arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. N1 is unsubstituted phenyl, unsubstituted naphthyl, or unsubstituted pyridyl. N1 is a substituted phenyl, substituted naphthyl, or substituted pyridyl.

[0197] In embodiments, R N1 C6~C 10 In embodiments, R N1 is phenyl (e.g., any phenyl described herein).

[0198] In embodiments, R N1 is a 5- to 10-membered heteroaryl (eg, any 5- to 10-membered heteroaryl described herein).

[0199] In an embodiment, A 1 teeth, [ka] is.

[0200] In an embodiment, A 1 teeth, [ka] is.

[0201] In an embodiment, A 1 teeth, [ka] is.

[0202] In embodiments, R A is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched halo In an embodiment, R is selected from the group consisting of alkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. A is an unsubstituted C1-C7 alkyl. In embodiments, R A is methyl.

[0203] In embodiments, aa is 0. In embodiments, aa is 1. In embodiments, aa is 2. In embodiments, aa is not 0. In embodiments, aa excludes 0. In embodiments, aa is 0 or 1. In embodiments, aa is 1 or 2.

[0204] In embodiments, R 2 is phenyl. In embodiments, R 2 is unsubstituted phenyl. In embodiments, R 2 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 2 is phenyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0205] In embodiments, R 2 is naphthyl. In embodiments, R 2 is unsubstituted naphthyl. In embodiments, R 2 is naphthyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is naphthyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0206] In embodiments, R 2is pyridyl. In embodiments, R 2 is unsubstituted pyridyl. In embodiments, R 2 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0207] In embodiments, R 2 is indolyl. In embodiments, R 2 is an unsubstituted indolyl. In embodiments, R 2 is an indolyl that includes at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0208] In embodiments, R 2 is phenyl, naphthyl, pyridyl or [ka] is.

[0209] In embodiments, R 2 teeth, [ka] where a is 0, 1, 2, or 3, and R 2a are each independently any substituent described herein. In embodiments, R 2aare each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 2a are each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0210] In embodiments, R 2 teeth, [ka] In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3.

[0211] In embodiments, R 3 is phenyl. In embodiments, R 3 is unsubstituted phenyl. In embodiments, R 3 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 3 is phenyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0212] In embodiments, R 3 is naphthyl. In embodiments, R 3 is unsubstituted naphthyl. In embodiments, R 3 has at least one halogen substituent (e.g., chloro or In one embodiment, R is a naphthyl containing at least one substituent that is a fluoro group. 3 is naphthyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0213] In embodiments, R 3 is pyridyl. In embodiments, R 3 is unsubstituted pyridyl. In embodiments, R 3 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0214] In embodiments, R 3 is indolyl. In embodiments, R3 is an unsubstituted indolyl. In embodiments, R 3 is an indolyl that includes at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0215] In embodiments, R 3 is phenyl, naphthyl, or pyridyl.

[0216] In embodiments, R 3 teeth, [ka] wherein a is 0, 1, 2, or 3, and each R 3a are independently any substituent described herein. In embodiments, R 3a are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 3aare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0217] In an embodiment, A 1 teeth [ka] where R 2ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, In an embodiment, R is selected from the group consisting of hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. a and R b are each methyl.

[0218] In embodiments, R a and R b are each ethyl.

[0219] In embodiments, R a and R b are linked to form a carbocyclic ring that is a C3-C7 cycloalkyl. a and R b are joined to form a carbocyclic ring that is an unsubstituted C3-C7 cycloalkyl. a and R b are joined to form a carbocyclic ring that is a substituted C3-C7 cycloalkyl. a and R b is linked to form a cyclopropyl (e.g., unsubstituted cyclopropyl). a and R bis joined to form a cyclobutyl (e.g., unsubstituted cyclobutyl). a and R b is joined to form a cyclopentyl (e.g., unsubstituted cyclopentyl). In embodiments, R a and R b are linked to form a cyclohexyl (eg, unsubstituted cyclohexyl).

[0220] In embodiments, R a and R b Combine the [ka] This forms a group which is

[0221] In embodiments, R 1 is C6~C 10 It is aryl.

[0222] In embodiments, R 1 is a five- to six-membered heteroaryl ring. 1 is imidazolyl (e.g., unsubstituted imidazolyl or N-methylimidazolyl). 1 is oxazolyl (e.g., unsubstituted oxazolyl). In embodiments, R 1 is isoxazolyl (eg, unsubstituted oxazolyl).

[0223] In embodiments, R 1 teeth [ka] wherein X is O, NH, or NCH3, aa1 is 0, 1, or 2, and R 1ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0224] In embodiments, R 1 teeth, [ka] In embodiments, R 1 teeth, [ka] is.

[0225] In embodiments, R 1 is a polar acyl group (e.g., the partial structure is [ka] In an embodiment, R 1is an acyl moiety containing a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6-membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6-membered nitrogen-containing heterocyclyl (e.g., azetidinyl, pyrrolidinyl, or piperidinyl), The group includes a substituent that is an amino group (e.g., -NH, monoalkylamino (e.g., -NHMe), or dialkylamino (e.g., -NMe)), an acetamide group (e.g., -NHCOMe or NMeCOMe), a carbamate group (e.g., -NHCOMe or -NMeCOMe), an alkylsulfonamide group (e.g., -NHSOMe or -NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, N-methylimidazolyl, pyridyl, or pyridazinyl). In embodiments, R 1 is an alkyl acyl group (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)).

[0226] In embodiments, R 1 excludes unsubstituted alkyl acyl groups (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)).

[0227] In embodiments, R 1 is a polar sulfonyl group (e.g., a moiety such as, as further described herein, [ka] ) In an embodiment, R 1is a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6-membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6-membered nitrogen-containing heterocyclyl (e.g., and sulfonyl moieties containing an amino group (e.g., -NH, monoalkylamino (e.g., -NHMe), or dialkylamino (e.g., -NMe)), an acetamido group (e.g., -NHCOMe or -NMeCOMe), an alkylsulfonamido group (e.g., -NHSOMe or -NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, N-methylimidazolyl, pyridyl, or pyridazinyl).

[0228] In embodiments, R 1 teeth, [ka] is selected from the group consisting of R 4a , R 4b , R 4c , R 6a , R 6b , and R 6c are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, or R 6a and R 6b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, and R4d and R 6d are each selected from the group consisting of phenyl, benzyl, pyridyl, —CH2(pyridyl), imidazole, and —CH2(imidazole); R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8boptionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; y 1 is 0, 1, or 2, and y 2 is 0, 1, or 2.

[0229] In embodiments, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j, and NHCONR 8f In embodiments, R 5 excludes unsubstituted C1-C7 alkyl. In embodiments, R 5 excludes unsubstituted C3-C7 cycloalkyl.

[0230] In embodiments, R 7 excludes unsubstituted C1-C7 alkyl. In embodiments, R 7 excludes unsubstituted C3-C7 cycloalkyl.

[0231] In embodiments, R 4d teeth, [ka] wherein R 4bb is H or CH3, a is 1 or 2, and each R 4aa are independently any substituent described herein. In embodiments, R 4aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 4aaare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0232] In embodiments, R 6d teeth, [ka] wherein R 6bb is H or CH3, a is 1 or 2, and each R 6aa are independently any substituent described herein. In embodiments, R 6aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 6aaare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0233] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0234] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0235] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0236] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0237] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0238] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0239] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0240] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0241] In an embodiment, y 1 is 0 and R 1 is COR 5 is.

[0242] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0243] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0244] In embodiments, R 4a is H. In an embodiment, R 4b is H. In an embodiment, R 4a and R 4b are both H. In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0245] In embodiments, R 4a and R 4b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 4a and R 4b together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0246] In embodiments, R 4c is H. In an embodiment, R 4d is phenyl. In embodiments, R 4d is benzyl. In embodiments, R 4d is pyridyl. In embodiments, R 4d is —CH (pyridyl). In embodiments, R 4d is imidazole. In embodiments, R 4d is —CH (imidazole). In embodiments, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0247] In embodiments, R 6a is H. In an embodiment, R 6b is H. In an embodiment, R 6a and R 6b are both H. In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0248] In embodiments, R 6a and R 6b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 6a and R bb together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0249] In embodiments, R 6c is H. In an embodiment, R 6d is phenyl. In embodiments, R 6d is benzyl. In embodiments, R 6d is pyridyl. In embodiments, R 6d is —CH (pyridyl). In embodiments, R 6dis imidazole. In embodiments, R 6d is —CH (imidazole). In embodiments, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0250] In embodiments, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is C3-C7 cyclofluoroalkyl. In an embodiment, R 5 is an unsubstituted C1-C7 alkyl. In embodiments, R 5 is a substituted C1-C7 alkyl (e.g., containing an amino substituent such as -NH2, -NHCH3, or -N(CH3)2). 5 is phenyl. In embodiments, R 5 is phenyl. In embodiments, R 5 is unsubstituted phenyl. In embodiments, R 5 is a substituted phenyl. In embodiments, R 5 is NR 8a R 8b In an embodiment, R 5 is SO2R 8c In an embodiment, R 5 is NR 8d SO2R 8e In an embodiment, R 5 NHCONR 8f In an embodiment, R 5 is NR 8g COR 8hIn an embodiment, R 5 is not unsubstituted C1-C7 alkyl.

[0251] In embodiments, R 7 is pyridyl. In embodiments, R 7 is pyridazine. In embodiments, R 7 is C1-C7 alkyl. In an embodiment, R 7 is C3-C7 cycloalkyl. In an embodiment, R 7 is C1-C7 haloalkyl. In embodiments, R 7 is C3-C7 cyclohaloalkyl. In embodiments, R 7 is C1-C7 fluoroalkyl. In an embodiment, R 7 is C3-C7 cyclofluoroalkyl. In an embodiment, R 7 is an unsubstituted C1-C7 alkyl. In embodiments, R 7 is a substituted C1-C7 alkyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is unsubstituted phenyl. In embodiments, R 7 is a substituted phenyl. In embodiments, R 7 is NR 8a R 8b In an embodiment, R 7 is SO2R 8c In an embodiment, R 7 is NR 8d SO2R 8e In an embodiment, R 7 NHCONR 8f In an embodiment, R 7 is not unsubstituted C1-C7 alkyl.

[0252] In embodiments, R 11 is hydrogen. In embodiments, R 11 is C1-C7 alkyl (e.g., methyl). In embodiments, R 11 is a C3-C7 cycloalkyl.

[0253] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, Z a is CH2 or O, Z a If is CH2, p 1 +p 2 is 1, 2, 3, or 4, and Z a If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 Both are non-zero.

[0254] In embodiments, R 1 teeth, [ka] where: Z b is CH2 or O, Z b If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z b If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0255] In embodiments, R 1 teeth, [ka] where: Z c is CH2 or O, Z c If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z c If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2are not both 0, R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0256] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, R 10a and R 10b are independently H, C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, SO2R8e , COOR 8j ,CONR 8f , and C.O.R. 8h and R 10a and R 10b at least one of is selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8e , R 8f , and R 8h are each selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, and R 8j is C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0257] In embodiments, R 1 COOR 5 where R 5 is C6~C 10 It is aryl or 5- to 10-membered heteroaryl.

[0258] In embodiments, R 1 teeth, [ka] where R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl.

[0259] In embodiments, R 1 teeth, [ka] where uu is 1 or 2.

[0260] In embodiments, R 1 teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0261] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0262] In embodiments, R 1 teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0263] In embodiments, R 1 teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0264] In embodiments, R 1 teeth, [ka] where R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is an unsubstituted C1-C7 alkyl.

[0265] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0266] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0267] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0268] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0269] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0270] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0271] In embodiments, R 1 teeth, [ka] is.

[0272] In embodiments, R 1 teeth, [ka] is.

[0273] In embodiments, R 1 teeth, [ka] is.

[0274] In embodiments, R 1 teeth, [ka] where R 8a , R 8b , and R 8gare each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0275] In embodiments, R 1 teeth, [ka] is.

[0276] In embodiments, R 1 teeth, [ka] is.

[0277] In embodiments, R 1 teeth, [ka] is.

[0278] In embodiments, R 1 teeth, [ka] is.

[0279] In embodiments, R 1 teeth, [ka] is.

[0280] In embodiments, R 1 teeth, [ka] is.

[0281] In embodiments, R 1 teeth, [ka] is.

[0282] In embodiments, R 1 teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0283] In embodiments, R 1 teeth, [ka] where R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h is independently unsubstituted C1-C7 alkyl.

[0284] In embodiments, R 1 teeth, [ka] is.

[0285] In embodiments, the compound of general formula (I) has a structure according to the following: [ka] Included are enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: R N is an unsubstituted C1-C7 alkyl, and R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2.

[0286] In embodiments, the compound of general formula (I) has a structure according to the following: [ka] In the formula, R N , R 2a , n, and a each according to any aspect or embodiment described herein.

[0287] In embodiments, the compound of general formula (I) has a structure according to the following: [ka] In the formula, R N , R 2a , n, and a each according to any aspect or embodiment described herein.

[0288] Compounds of general formula (II) Described herein are compounds of general formula (II), as well as exemplary embodiments of general formula (II).

[0289] The exemplary general formulas and compounds described herein may also include hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0290] In one aspect, the invention features a compound having a structure according to the following general formula (II): [ka] Included are enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: R N2 is hydrogen, C1-C7 alkyl, C6-C 10 aryl, or 5- to 10-membered heteroaryl; A 2 teeth, [ka] is selected from the group consisting of R 1 is C6~C 10 an aryl, a five- or six-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R 3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, and R A is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2- selected from the group consisting of C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; aa is 0, 1, or 2; m is 1, 2, or 3; and n is 1, 2, 3, or 4.

[0291] In embodiments, n is 1. In embodiments, n is 2. In embodiments, n is 3. In embodiments, n is 4.

[0292] In embodiments, R N2 is hydrogen.

[0293] In embodiments, R N2 is C1-C7 alkyl. In an embodiment, R N2 is methyl, ethyl, or isopropyl.

[0294] In embodiments, R N2 is C6~C 10 In embodiments, R N2 is a 5- to 10-membered heteroaryl. In embodiments, the aryl or heteroaryl is unsubstituted. In embodiments, the aryl or heteroaryl may be the same or different and may be selected from C1 to C7 straight chain alkyl, C3 to C7 branched alkyl, C3 to C7 cycloalkyl, C 1~ C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, aryl In an embodiment, R is substituted with one or more substituents selected from the group consisting of arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. N2 is unsubstituted phenyl, unsubstituted naphthyl, or unsubstituted pyridyl. N2 is a substituted phenyl, substituted naphthyl, or substituted pyridyl.

[0295] In embodiments, R N2 is C6~C 10 In embodiments, R N2 is phenyl.

[0296] In embodiments, R N2 is a 5- to 10-membered heteroaryl.

[0297] In an embodiment, A 2 teeth, [ka] is.

[0298] In an embodiment, A 2 teeth, [ka] is.

[0299] In an embodiment, A 2 teeth, [ka] is.

[0300] In embodiments, R Ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, In an embodiment, R is selected from the group consisting of hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. A is an unsubstituted C1-C7 alkyl. In embodiments, R A is methyl.

[0301] In embodiments, aa is 0. In embodiments, aa is 1. In embodiments, aa is 2. In embodiments, aa is not 0. In embodiments, aa excludes 0. In embodiments, aa is 0 or 1. In embodiments, aa is 1 or 2.

[0302] In embodiments, R 2 is phenyl. In embodiments, R 2 is unsubstituted phenyl. In embodiments, R 2 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 2 is phenyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0303] In embodiments, R 2 is naphthyl. In embodiments, R 2 is unsubstituted naphthyl. In embodiments, R 2 is naphthyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is selected from OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, morpholino, CO2H, CO2CH3, and CO2NH2; and naphthyl substituted with one, two, or three groups (eg, one or two groups).

[0304] In embodiments, R 2 is pyridyl. In embodiments, R 2 is unsubstituted pyridyl. In embodiments, R 2 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0305] In embodiments, R 2 is indolyl. In embodiments, R2 is an unsubstituted indolyl. In embodiments, R 2 is an indolyl that includes at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0306] In embodiments, R 2 is phenyl, naphthyl, pyridyl or [ka] is.

[0307] In embodiments, R 2 teeth, [ka] where a is 0, 1, 2, or 3, and R 2a are each independently any substituent described herein. In embodiments, R 2a are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 2aare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0308] In embodiments, R 2 teeth, [ka] In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3.

[0309] In embodiments, R 3 is phenyl. In embodiments, R 3 is unsubstituted phenyl. In embodiments, R 3 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 3is phenyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0310] In embodiments, R 3 is naphthyl. In embodiments, R 3 is unsubstituted naphthyl. In embodiments, R 3 is naphthyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is naphthyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0311] In embodiments, R 3 is pyridyl. In embodiments, R 3 is unsubstituted pyridyl. In embodiments, R 3 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0312] In embodiments, R 3 is indolyl. In embodiments, R 3 is an unsubstituted indolyl. In embodiments, R 3 is an indolyl that includes at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0313] In embodiments, R 3 is phenyl, naphthyl, or pyridyl.

[0314] In embodiments, R 3 teeth, [ka] wherein a is 0, 1, 2, or 3, and each R 3a are independently any substituent described herein. In embodiments, R 3a are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 CH2CH3, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 3aare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. 2 teeth [ka] where R 2ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0315] In embodiments, R 1 is C6~C 10 It is aryl.

[0316] In embodiments, R 1 is a five- to six-membered heteroaryl ring. 1 is imidazolyl (e.g., unsubstituted imidazolyl or N-methylimidazolyl). 1 is oxazolyl (e.g., unsubstituted oxazolyl). In embodiments, R 1 is isoxazolyl (eg, unsubstituted oxazolyl).

[0317] In embodiments, R 1 teeth, [ka] wherein X is O, NH, or NCH3, aa1 is 0, 1, or 2, and R 1ais C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0318] In embodiments, R 1 teeth, [ka] In embodiments, R 1 teeth, [ka] is.

[0319] In embodiments, R 1 is a polar acyl group (e.g., the partial structure is [ka] ) In an embodiment, R 1is a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6-membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6-membered nitrogen-containing heterocyclyl (e.g., azetidinyl, pyrrolidinyl, or piperidinyl), which groups contain a substituent that is an amino group (e.g., —NH, monoalkylamino (e.g., —NHMe), or dialkylamino (e.g., —NMe)), an acetamide group (e.g., —NHCOMe or —NMeCOMe), a carbamate group (e.g., —NHCOMe or —NMeCOMe), an alkylsulfonamide group (e.g., —NHSOMe or —NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, N-methylimidazolyl, pyridyl, or pyridazinyl). In embodiments, R 1 is an alkyl acyl group (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)). In embodiments, R 1 excludes unsubstituted alkyl acyl groups (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)).

[0320] In embodiments, R 1 is a polar sulfonyl group (e.g., a moiety such as, as further described herein, [ka] ) In an embodiment, R 1is a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6 membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6 membered nitrogen-containing heterocyclyl (e.g., , azetidinyl, pyrrolidinyl, or piperidinyl), which groups contain a substituent that is an amino group (e.g., -NH, monoalkylamino (e.g., -NHMe), or dialkylamino (e.g., -NMe)), an acetamide group (e.g., -NHCOMe or -NMeCOMe), an alkylsulfonamide group (e.g., -NHSOMe or -NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, or N-methylimidazolyl, pyridyl, or pyridazinyl).

[0321] In embodiments, R 1 teeth, [ka] is selected from the group consisting of R 4a , R 4b , R 4c , R 6a , R 6b , and R 6c are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, or R 6a and R 6b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, and R4d and R 6d are each selected from the group consisting of phenyl, benzyl, pyridyl, —CH2(pyridyl), imidazole, and —CH2(imidazole); R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3 ~C7 cycloalkoxy, C1~C7 haloalkyl, C3~C7 cyclohaloalkyl, C1~C7 haloalkoxy, C3~C7 cyclohaloalkoxy, C6~C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8boptionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; y 1 is 0, 1, or 2, and y 2 is 0, 1, or 2.

[0322] In embodiments, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j, NHCONR 8f In embodiments, R 5 excludes unsubstituted C1-C7 alkyl. In embodiments, R 5 excludes unsubstituted C3-C7 cycloalkyl.

[0323] In embodiments, R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f In embodiments, R 7 excludes unsubstituted C1-C7 alkyl. In embodiments, R 7 excludes unsubstituted C3-C7 cycloalkyl.

[0324] In embodiments, R 4d teeth, [ka] wherein R 4bb is H or CH3, a is 1 or 2, and each R 4aa are independently any substituent described herein. In embodiments, R 4aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 4aaare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0325] In embodiments, R 6d teeth, [ka] wherein R 6bb is H or CH3, a is 1 or 2, and each R 6aa are independently any substituent described herein. In embodiments, R 6aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 6aaeach independently represents C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, Oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0326] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0327] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0328] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0329] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0330] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. So, y 2 is 2.

[0331] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0332] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1is 1. In an embodiment, y 1 is 2.

[0333] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0334] In an embodiment, y 1 is 0 and R 1 is COR 5 In an embodiment, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is a C3-C7 cyclofluoroalkyl.

[0335] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0336] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0337] In embodiments, R 4a is H. In an embodiment, R 4bis H. In an embodiment, R 4a and R 4b are both H. In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0338] In embodiments, R 4a and R 4b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 4a and R 4b together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0339] In embodiments, R 4c is H. In an embodiment, R 4d is phenyl. In embodiments, R 4d is benzyl. In embodiments, R 4d is pyridyl. In embodiments, R 4d is —CH (pyridyl). In embodiments, R 4d is imidazole. In embodiments, R 4d is —CH (imidazole). In embodiments, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0340] In embodiments, R 6a is H. In an embodiment, R 6b is H. In an embodiment, R 6a and R 6b are both H. In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0341] In embodiments, R 6a and R 6bare taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 6a and R bb together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0342] In embodiments, R 6c is H. In an embodiment, R 6d is phenyl. In embodiments, R 6d is benzyl. In embodiments, R 6d is pyridyl. In embodiments, R 6d is —CH (pyridyl). In embodiments, R 6d is imidazole. In embodiments, R 6d is —CH (imidazole). In embodiments, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0343] In embodiments, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is C3-C7 cyclofluoroalkyl. In an embodiment, R 5 is an unsubstituted C1-C7 alkyl. In embodiments, R 5 is a substituted C1-C7 alkyl (e.g., containing an amino substituent such as -NH2, -NHCH3, or -N(CH3)2). 5 is phenyl. In embodiments, R 5is phenyl. In embodiments, R 5 is unsubstituted phenyl. In embodiments, R 5 is a substituted phenyl. In embodiments, R 5 is NR 8a R 8b In an embodiment, R 5 is SO2R 8c In an embodiment, R 5 is NR 8d SO2R 8e In an embodiment, R 5 NHCONR 8f In an embodiment, R 5 is NR 8g COR 8h In an embodiment, R 5 is not unsubstituted C1-C7 alkyl.

[0344] In embodiments, R 7 is pyridyl. In embodiments, R 7 is pyridazine. In embodiments, R 7 is C1-C7 alkyl. In an embodiment, R 7 is C3-C7 cycloalkyl. In an embodiment, R 7 is C1-C7 haloalkyl. In embodiments, R 7 is C3-C7 cyclohaloalkyl. In embodiments, R 7 is C1-C7 fluoroalkyl. In an embodiment, R 7 is C3-C7 cyclofluoroalkyl. In an embodiment, R 7 is an unsubstituted C1-C7 alkyl. In embodiments, R 7 is a substituted C1-C7 alkyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is unsubstituted phenyl. In embodiments, R 7 is a substituted phenyl. In embodiments, R 7 is NR 8a R 8b In an embodiment, R7 is SO2R 8c In an embodiment, R 7 is NR 8d SO2R 8e In an embodiment, R 7 NHCONR 8f In an embodiment, R 7 is not unsubstituted C1-C7 alkyl.

[0345] In embodiments, R 11 is hydrogen. In embodiments, R 11 is C1-C7 alkyl (e.g., methyl). In embodiments, R 11 is a C3-C7 cycloalkyl.

[0346] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, Z a is CH2 or O, Z a If is CH2, p 1 +p 2 is 1, 2, 3, or 4, and Z a If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 Both are non-zero.

[0347] In embodiments, R 1 teeth, [ka] where: Z b is CH2 or O, Z b If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z b If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0348] In embodiments, R 1 teeth, [ka] where: Z c is CH2 or O, Z c If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z c If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8hare each C1-C7 alkyl or C3-C7 cycloalkyl.

[0349] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, R 10a and R 10b are independently H, C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, SO2R 8e , COOR 8j ,CONR 8f , and C.O.R. 8h and R 10a and R 10b at least one of is selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8e , R 8f , and R 8h are each selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8j is C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0350] In embodiments, R 1 COOR 5 where R 5 is C6~C 10 It is aryl or 5- to 10-membered heteroaryl.

[0351] In embodiments, R 1 teeth, [ka] where R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl.

[0352] In embodiments, R 1 teeth, [ka] where uu is 1 or 2.

[0353] In embodiments, R 1 teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0354] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0355] In embodiments, R 1 teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0356] In embodiments, R 1 teeth, [ka] where R 8a and R 8b are each independently H or an unsubstituted C1-C7 alkyl group. It's Rukiru.

[0357] In embodiments, R 1 teeth, [ka] where R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is an unsubstituted C1-C7 alkyl.

[0358] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0359] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0360] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0361] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0362] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0363] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0364] In embodiments, R 1 teeth, [ka] is.

[0365] In embodiments, R 1 teeth, [ka] is.

[0366] In embodiments, R 1 teeth, [ka] is.

[0367] In embodiments, R 1 teeth, [ka] where R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0368] In embodiments, R 1 teeth, [ka] is.

[0369] In embodiments, R 1 teeth, [ka] is.

[0370] In embodiments, R 1 teeth, [ka] is.

[0371] In embodiments, R 1 teeth, [ka] is.

[0372] In embodiments, R 1 teeth, [ka] is.

[0373] In embodiments, R 1 teeth, [ka] is.

[0374] In embodiments, R 1 teeth, [ka] is.

[0375] In embodiments, R 1 teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0376] In embodiments, R 1 teeth, [ka] where R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h is independently unsubstituted C1-C7 alkyl.

[0377] In embodiments, R 1 teeth, [ka] is.

[0378] In embodiments, the compound according to general formula (II) has the following structure: [ka] Included are enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: R N , R 1 and n each being, according to any aspect or embodiment described herein, R 2a are each independently halogen, unsubstituted C1-C7 alkyl, C1-C7 perhaloalkyl, unsubstituted C1-C7 alkoxy, C1-C7 perhaloalkoxy, or CN; a is 0, 1, or 2.

[0379] In embodiments, the compound according to general formula (II) has the following structure: [ka] In the formula, R N , R 1 , R 2a , n, and a each according to any aspect or embodiment described herein.

[0380] In embodiments, the compound according to general formula (II) has the following structure: [ka] In the formula, R N , R 1 , R 2a , n, and a each according to any aspect or embodiment described herein.

[0381] Compounds of general formula (III) Described herein are compounds of general formula (III), as well as exemplary embodiments of general formula (III).

[0382] The exemplary general formulas and compounds described herein may also include hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0383] In one aspect, the invention features a compound having a structure according to the following general formula (III): [ka] Included are enantiomers, diastereomers, hydrates, solvates, pharmaceutically acceptable salts, prodrugs, and complexes thereof, wherein: R a and R b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 branched alkyl, or R a and R b together with the atoms to which they are attached form a ring having 5 to 7 ring atoms, optionally containing a double bond, or R a and R b together with the atoms to which they are attached, are O, S, SO, SO2 and NR 1 forming a ring having 6 to 8 ring atoms containing a moiety selected from the group consisting of R N3 is hydrogen, C1-C7 alkyl, C6-C 10 heteroaryl, or 5- to 10-membered heteroaryl; A 3 is an N-linked, 5- to 12-membered nitrogen-containing heterocyclyl, which may be monocyclic, bicyclic, or polycyclic and optionally contain additional heteroatoms selected from O, N, and S, and non-aromatic nitrogen-containing heterocyclyls are represented by R 2 further comprising a group, R 1 is H, C1-C7 alkyl, C3-C7 cycloalkyl, phenyl, benzyl, a 5- to 6-membered heteroaryl ring, a polar acyl group, or a polar sulfonyl group; R 2 is a 6- to 10-membered aryl, a 5- to 10-membered nitrogen-containing heteroaryl, and [ka] is selected from the group consisting of R3 is a 6- to 10-membered aryl or a 5- to 10-membered nitrogen-containing heteroaryl, m is 1, 2, or 3, and n is 1, 2, 3, or 4.

[0384] In embodiments, R N If is hydrogen, A is [ka] Instead, in the formula, R A is phenyl, (CH2) 1~3 -(phenyl), naphthyl, (CH2) 1~3 -(naptyl), pyridyl, or (CH2) 1~3 -(pyridyl) group.

[0385] In embodiments, R a and R b together with the atoms to which they are attached form a ring having 6 to 8 ring atoms, one of which is O, S, SO, SO2, and NR 1 is a moiety selected from the group consisting of:

[0386] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R a , R b , R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0387] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R a , R b , R N3 , A 3, and n according to any aspect or embodiment described herein.

[0388] In embodiments, R a and R b together with the atoms to which they are attached form a ring having 6 to 8 ring atoms, one of which is O, S, SO, SO2, and NR 1 is a moiety selected from the group consisting of:

[0389] In embodiments, R N3 is hydrogen.

[0390] In embodiments, R N3 is a C1-C7 alkyl.

[0391] In embodiments, R N3 is C6~C 10 In embodiments, R N3 is a 5- to 10-membered heteroaryl. In embodiments, the aryl or heteroaryl is unsubstituted. In embodiments, the aryl or heteroaryl may be the same or different and may be selected from C1 to C7 straight chain alkyl, C3 to C7 branched alkyl, C3 to C7 cycloalkyl, C 1~C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, aryl In an embodiment, R is substituted with one or more substituents selected from the group consisting of arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen. N is unsubstituted phenyl, unsubstituted naphthyl, or unsubstituted pyridyl. N is a substituted phenyl, substituted naphthyl, or substituted pyridyl.

[0392] In embodiments, R a and R b are each methyl.

[0393] In embodiments, R a and R b are each ethyl.

[0394] In embodiments, R a and R b are joined to form an unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. a and R b is attached to form an unsubstituted cyclopropyl. a and R b is attached to form an unsubstituted cyclobutyl. a and Rb is attached to form an unsubstituted cyclopentyl. a and R b is attached to form an unsubstituted cyclohexyl.

[0395] In embodiments, R a and R b together with the atoms to which they are attached, form NR 1 Forms a ring having 6 to 8 ring atoms, including a moiety

[0396] In embodiments, R a and R b together with the atoms to which they are attached form a ring having 6 to 8 ring atoms, one of which is NR 1 This is the part that is.

[0397] In embodiments, R a and R b Combine the [ka] This forms a group which is

[0398] In an embodiment, A 3 teeth, [ka] is selected from the group consisting of During the ceremony, R 2 is phenyl, naphthyl, pyridyl, indolyl, and [ka] is selected from the group consisting of R 3 is selected from the group consisting of phenyl, naphthyl, pyridyl, and indolyl; R A is C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C 1~C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C 1~ selected from the group consisting of C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; and aa is 0, 1, or 2.

[0399] In embodiments, R A is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, In an embodiment, R is selected from the group consisting of hydroxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.A is a C1-C7 linear alkyl. A is an unsubstituted C1-C7 alkyl. In embodiments, R A is methyl.

[0400] In an embodiment of general formula (III), aa is 0.

[0401] In an embodiment of general formula (III), aa is 1.

[0402] In an embodiment of general formula (III), aa is 2.

[0403] In an embodiment, A 3 teeth, [ka] No.

[0404] In an embodiment, A 3 teeth, [ka] Exclude.

[0405] In an embodiment, A 3 teeth, [ka] wherein A is selected from the group consisting of 3 teeth, [ka] No.

[0406] In an embodiment, A 3 teeth, [ka] is.

[0407] In an embodiment, A 3 teeth, [ka] is.

[0408] In an embodiment, A 3 teeth, [ka] is.

[0409] In an embodiment, A 3 teeth, [ka] is.

[0410] In an embodiment, A 3 teeth, [ka] is.

[0411] In an embodiment, A 3 teeth, [ka] is.

[0412] In an embodiment, A 3 teeth, [ka] is.

[0413] In an embodiment, A 3 teeth, [ka] is.

[0414] In an embodiment, A 3 teeth, [ka] is.

[0415] In an embodiment, A 3 teeth, [ka] is.

[0416] In an embodiment, A 3 teeth, [ka] is.

[0417] In an embodiment, A 3 teeth, [ka] is.

[0418] In an embodiment, A 3 teeth, [ka] is.

[0419] In an embodiment, A 3 teeth, [ka] is.

[0420] In an embodiment, A 3 teeth, [ka] is.

[0421] In an embodiment, A 3 teeth, [ka] is.

[0422] In an embodiment, A 3 teeth, [ka] is.

[0423] In an embodiment, A 3 teeth, [ka] is.

[0424] In an embodiment, A 3 teeth, [ka] is.

[0425] In an embodiment, A 3 teeth, [ka] is.

[0426] In an embodiment, A 3 teeth, [ka] is.

[0427] In an embodiment, A 3 teeth, [ka] is.

[0428] In an embodiment, A 3 teeth, [ka] is.

[0429] In an embodiment, A 3 teeth, [ka] is.

[0430] In an embodiment, A 3 teeth, [ka] is.

[0431] In an embodiment, A 3 teeth, [ka] is.

[0432] In an embodiment, A 3 teeth, [ka] is.

[0433] In an embodiment, A 3 teeth, [ka] is.

[0434] In an embodiment, A 3 teeth, [ka] is.

[0435] In an embodiment, A 3 teeth, [ka] is.

[0436] In an embodiment, A 3 teeth, [ka] is.

[0437] In an embodiment, A 3 teeth, [ka] is.

[0438] In an embodiment, A 3 teeth, [ka] is.

[0439] In an embodiment, A 3 teeth, [ka] is.

[0440] In an embodiment, A 3 teeth, [ka] is.

[0441] In an embodiment, A 3 teeth, [ka] is.

[0442] In an embodiment, A 3 teeth, [ka] is.

[0443] In an embodiment, A 3 teeth, [ka] is.

[0444] In an embodiment, A 3 teeth, [ka] is.

[0445] In an embodiment, A 3 teeth, [ka] is.

[0446] In an embodiment, A 3 teeth, [ka] is.

[0447] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0448] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0449] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0450] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] (III-B), where R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0451] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N , A 3 , and n according to any aspect or embodiment described herein.

[0452] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N , A 3 , and n according to any aspect or embodiment described herein.

[0453] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N , A 3, and n according to any aspect or embodiment described herein.

[0454] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0455] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0456] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0457] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0458] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0459] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0460] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0461] In embodiments, the compound according to general formula (III) has a structure according to the following general formula: [ka] In the formula, R N3 , A 3 , and n according to any aspect or embodiment described herein.

[0462] In embodiments, R 2 is phenyl. In embodiments, R 2 is unsubstituted phenyl. In embodiments, R 2 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 2 is phenyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0463] In embodiments, R 2 is naphthyl. In embodiments, R 2 is unsubstituted naphthyl. In embodiments, R 2 is naphthyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is naphthyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0464] In embodiments, R 2 is pyridyl. In embodiments, R 2 is unsubstituted pyridyl. In embodiments, R 2 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 2 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0465] In embodiments, R 2 is indolyl. In embodiments, R 2is an unsubstituted indolyl. In embodiments, R 2 is an indolyl that contains at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). , R 2 is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0466] In embodiments, R 2 is phenyl, naphthyl, pyridyl or [ka] is.

[0467] In embodiments, R 2 teeth, [ka] where a is 0, 1, 2, or 3, and R 2a are each independently any substituent described herein. In embodiments, R 2a are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 2aare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0468] In embodiments, R 2 teeth, [ka] In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3.

[0469] In embodiments, R 3 is phenyl. In embodiments, R 3 is unsubstituted phenyl. In embodiments, R 3 is phenyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is fluorophenyl (e.g., 2-, 3-, or 4-fluorophenyl), difluorophenyl, chlorophenyl (e.g., 2-, 3-, or 4-chlorophenyl), dichlorophenyl, chlorofluorophenyl. 3are OH, OCH3, NH2, CN, CH3, CF3, CH2CH3, isopropyl, F, Cl, Br, mol and phenyl substituted with one, two, or three groups (eg, one or two groups) selected from phenyl, CO2H, CO2CH3, and CO2NH2.

[0470] In embodiments, R 3 is naphthyl. In embodiments, R 3 is unsubstituted naphthyl. In embodiments, R 3 is naphthyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is naphthyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0471] In embodiments, R 3 is pyridyl. In embodiments, R 3 is unsubstituted pyridyl. In embodiments, R 3 is pyridyl containing at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3 is pyridyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0472] In embodiments, R 3 is indolyl. In embodiments, R 3 is an unsubstituted indolyl. In embodiments, R 3 is an indolyl that includes at least one halogen substituent (e.g., at least one substituent that is a chloro or fluoro group). 3is indolyl substituted with one, two, or three groups (e.g., one or two groups) selected from OH, OCH, NH, CN, CH, CF, CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH.

[0473] In embodiments, R 3 is phenyl, naphthyl, or pyridyl.

[0474] In embodiments, R 3 teeth, [ka] wherein a is 0, 1, 2, or 3, and each R 3a are independently any substituent described herein. In embodiments, R 3a are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 3a each independently represents C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, 1 to 4 carbon atoms selected from the group consisting of methyl, methylamino, methylphenyl ... and 5- to 6-membered heterocyclic groups each containing a heteroatom of the formula:

[0475] In certain embodiments, A 3 teeth [ka] where R 2a is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0476] In embodiments, R 1 C6~C 10 It is aryl.

[0477] In embodiments, R 1 is a five- to six-membered heteroaryl ring. 1 is imidazolyl (e.g., unsubstituted imidazolyl or N-methylimidazolyl). 1 is oxazolyl (e.g., unsubstituted oxazolyl). In embodiments, R 1 is isoxazolyl (eg, unsubstituted oxazolyl).

[0478] In embodiments, R 1 teeth [ka] wherein X is O, NH, or NCH3, aa1 is 0, 1, or 2, and R 1a is C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy, and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0479] In embodiments, R 1 teeth, [ka] In embodiments, R 1 teeth, [ka] is.

[0480] In embodiments, R 1 is a polar acyl group (e.g., the partial structure is [ka] In an embodiment, R 1 is a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6-membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6-membered nitrogen-containing heterocyclyl (e.g., azetidinyl, pyrrolidinyl, or piperidinyl), which groups contain a substituent that is an amino group (e.g., —NH, monoalkylamino (e.g., —NHMe), or dialkylamino (e.g., —NMe)), an acetamide group (e.g., —NHCOMe or —NMeCOMe), a carbamate group (e.g., —NHCOMe or —NMeCOMe), an alkylsulfonamide group (e.g., —NHSOMe or —NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, N-methylimidazolyl, pyridyl, or pyridazinyl). In embodiments, R 1 is an alkyl acyl group (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)). In embodiments, R 1 excludes unsubstituted alkyl acyl groups (e.g., —C(O)(C1-C7 alkyl) or —C(O)(C3-C7 cycloalkyl)).

[0481] In embodiments, R 1 is a polar sulfonyl group (e.g., a moiety such as, as further described herein, [ka] ) In an embodiment, R 1is a C1-C7 alkyl group, a C3-C7 cycoalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), a C1-C7 haloalkyl group, a C3-C7 cycohaloalkyl group (e.g., cyclohalopropyl, cyclohalobutyl, cyclohalopentyl, or cyclohalohexyl), a 4-6-membered oxygen-containing heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or oxazalidonone), or a 4-6-membered nitrogen-containing heterocyclyl (e.g., and sulfonyl moieties containing an amino group (e.g., -NH, monoalkylamino (e.g., -NHMe), or dialkylamino (e.g., -NMe)), an acetamido group (e.g., -NHCOMe or -NMeCOMe), an alkylsulfonamido group (e.g., -NHSOMe or -NMeSOMe), or a 5- to 10-membered nitrogen-containing heterocyclyl (e.g., tetrazolyl, imidazolyl, N-methylimidazolyl, pyridyl, or pyridazinyl).

[0482] In embodiments, R 1 teeth, [ka] is selected from the group consisting of R 4a , R 4b , R 4c , R 6a , R 6b , and R 6c are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 4a and R 4b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, or R 6a and R 6b optionally, together with the atoms to which they are attached, form a ring containing 3 to 7 atoms, optionally containing oxygen, and R4d and R 6d are each selected from the group consisting of phenyl, benzyl, pyridyl, —CH2(pyridyl), imidazole, and —CH2(imidazole); R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , N.R. 8i COOR 8j , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 8i are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8boptionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl, R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl; or R 4a and R 8a If both exist, or R 4a and R 8g when both are present, these groups, optionally together with the atoms to which they are attached, form a ring containing 4 to 7 atoms; R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 11 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; y 1 is 0, 1, or 2, and y 2 is 0, 1, or 2.

[0483] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0484] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0485] In embodiments, R 4ais H. In an embodiment, R 4b is H. In an embodiment, R 4a and R 4b are both H. In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0486] In embodiments, R 4a and R 4b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 4a and R 4b together with the atoms to which they are attached form an oxygen-containing ring containing 3 to 7 atoms.

[0487] In embodiments, R 4c is H. In an embodiment, R 4d is phenyl. In embodiments, R 4d is benzyl. In embodiments, R 4d is pyridyl. In embodiments, R 4d is —CH (pyridyl). In embodiments, R 4d is imidazole. In embodiments, R 4d is —CH (imidazole). In embodiments, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0488] In embodiments, R 6a is H. In an embodiment, R 6b is H. In an embodiment, R 6a and R 6b are both H. In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0489] In embodiments, Rba and R 6b are taken together with the atoms to which they are attached to form a carbocyclic ring containing from 3 to 7 atoms. In embodiments, R 4a and R 4b are those together with the atom to which it is attached form an oxygen-containing ring containing 3 to 7 atoms.

[0490] In embodiments, R 6c is H. In an embodiment, R 6d is phenyl. In embodiments, R 6d is benzyl. In embodiments, R 6d is pyridyl. In embodiments, R 6d is —CH (pyridyl). In embodiments, R 6d is imidazole. In embodiments, R 6d is —CH (imidazole). In embodiments, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0491] In embodiments, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is C3-C7 cyclofluoroalkyl. In an embodiment, R 5 is an unsubstituted C1-C7 alkyl. In embodiments, R 5 is a substituted C1-C7 alkyl (e.g., containing an amino substituent such as -NH2, -NHCH3, or -N(CH3)2). 5is phenyl. In embodiments, R 5 is phenyl. In embodiments, R 5 is unsubstituted phenyl. In embodiments, R 5 is a substituted phenyl. In embodiments, R 5 is NR 8a R 8b In an embodiment, R 5 is SO2R 8c In an embodiment, R 5 is NR 8d SO2R 8e In an embodiment, R 5 is NR 8i COOR 8j In an embodiment, R 5 NHCONR 8f In an embodiment, R 5 is NR 8g COR 8h In an embodiment, R 5 is not unsubstituted C1-C7 alkyl.

[0492] In embodiments, R 7 is pyridyl. In embodiments, R 7 is pyridazine. In embodiments, R 7 is C1-C7 alkyl. In an embodiment, R 7 is C3-C7 cycloalkyl. In an embodiment, R 7 is C1-C7 haloalkyl. In embodiments, R 7 is C3-C7 cyclohaloalkyl. In embodiments, R 7 is C1-C7 fluoroalkyl. In an embodiment, R 7 is C3-C7 cyclofluoroalkyl. In an embodiment, R 7 is an unsubstituted C1-C7 alkyl. In embodiments, R 7 is a substituted C1-C7 alkyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is unsubstituted phenyl. In embodiments, R7 is a substituted phenyl. In embodiments, R 7 is NR 8a R 8b In an embodiment, R 7 is SO2R 8c In an embodiment, R 7 is NR 8d SO2R 8e In an embodiment, R 7 NHCONR 8f In an embodiment, R 7 is not unsubstituted C1-C7 alkyl.

[0493] In embodiments, R 4d teeth, [ka] wherein R 4bb is H or CH3, a is 1 or 2, and each R 4aa are independently any substituent described herein. In embodiments, R 4aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 4aa are each independently, C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C7 alkoxy and 5- or 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0494] In embodiments, R 6d teeth, [ka] wherein R 6bb is H or CH3, a is 1 or 2, and each R 6aa are independently any substituent described herein. In embodiments, R 6aa are each independently OH, OCH3, NH2, CN, CH3, and CF 3、 In embodiments, R is selected from CHCH, isopropyl, F, Cl, Br, morpholino, COH, COCH, and CONH. 6aaare each independently C1-C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C7 straight chain alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, aryloxy, C1-C7 straight chain haloalkyl, C3-C7 branched haloalkyl, C3-C7 cyclohaloalkyl, C2-C7 alkenyl, C2-C7 cycloalkenyl, C2-C7 alkynyl, aryl, arylalkyl, nitro, hydroxy, mercapto, oxo, thioxo, cyano, carbamoyl, carboxyl, C1-C 7 alkoxycarbonyl, sulfo, halogen, C1-C7 alkylthio, arylthio, C1-C7 alkylsulfinyl, arylsulfinyl, C1-C7 alkylsulfonyl, arylsulfonyl, amino, C1-C7 acylamino, mono- or di-C1-C7 alkylamino, C3-C7 cycloalkylamino, arylamino, C2-C7 acyl, arylcarbonyl, and 5- to 6-membered heterocyclic groups each containing 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen.

[0495] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0496] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0497] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0498] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0499] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0500] In embodiments, R 1 teeth, [ka] In an embodiment, y 2 is 0. In an embodiment, y 2 is 1. In an embodiment, y 2 is 2.

[0501] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0502] In embodiments, R 1 teeth, [ka] In an embodiment, y 1 is 0. In an embodiment, y 1 is 1. In an embodiment, y 1 is 2.

[0503] In an embodiment, y 1 is 0 and R 1 is COR 5 In an embodiment, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5 is C1-C7 fluoroalkyl. In an embodiment, R 5 is a C3-C7 cyclofluoroalkyl.

[0504] In embodiments, R 5 is pyridyl. In embodiments, R 5 is pyridazine. In embodiments, R 5 is C1-C7 alkyl. In an embodiment, R 5 is C3-C7 cycloalkyl. In an embodiment, R 5 is C1-C7 haloalkyl. In embodiments, R 5 is C3-C7 cyclohaloalkyl. In embodiments, R 5is C1-C7 fluoroalkyl. In an embodiment, R 5 is C3-C7 cyclofluoroalkyl. In an embodiment, R 5 is an unsubstituted C1-C7 alkyl. In embodiments, R 5 is a substituted C1-C7 alkyl (e.g., containing an amino substituent such as -NH2, -NHCH3, or -N(CH3)2). 5 is phenyl. In embodiments, R 5 is phenyl. In embodiments, R 5 is unsubstituted phenyl. In embodiments, R 5 is a substituted phenyl. In embodiments, R 5 is NR 8a R 8b In an embodiment, R 5 is SO2R 8c In an embodiment, R 5 is NR 8d SO2R 8e In an embodiment, R 5 NHCONR 8f Implementation In this state, R 5 is NR 8g COR 8h is.

[0505] In embodiments, R 7 is pyridyl. In embodiments, R 7 is pyridazine. In embodiments, R 7 is C1-C7 alkyl. In an embodiment, R 7 is C3-C7 cycloalkyl. In an embodiment, R 7 is C1-C7 haloalkyl. In embodiments, R 7 is C3-C7 cyclohaloalkyl. In embodiments, R 7 is C1-C7 fluoroalkyl. In an embodiment, R 7 is C3-C7 cyclofluoroalkyl. In an embodiment, R 7 is an unsubstituted C1-C7 alkyl. In embodiments, R 7is a substituted C1-C7 alkyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is phenyl. In embodiments, R 7 is unsubstituted phenyl. In embodiments, R 7 is a substituted phenyl. In embodiments, R 7 is NR 8a R 8b In an embodiment, R 7 is SO2R 8c In an embodiment, R 7 is NR 8d SO2R 8e In an embodiment, R 7 NHCONR 8f is.

[0506] In embodiments, R 11 is hydrogen. In embodiments, R 11 is C1-C7 alkyl (e.g., methyl). In embodiments, R 11 is a C3-C7 cycloalkyl.

[0507] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, Z a is CH2 or O, Z a If is CH2, p 1 +p 2 is 1, 2, 3, or 4, and Z a If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 Both are non-zero.

[0508] In embodiments, R 1 teeth, [ka] where: Z b is CH2 or O, Z b If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z b If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 5 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 aryl, 5 10-10 membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f , N.R. 8g COR 8h , and [ka] is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9 are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8boptionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0509] In embodiments, R 1 teeth, [ka] where: Z c is CH2 or O, Z c If is CH2, p 1 +p 2 is 1, 2, 3, or 4, Z c If is O, then p 1 +p 2 is 1, 2, 3, or 4, and p 1 and p 2 are not both 0, R 7 is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy, C3-C7 cycloalkoxy, C1-C7 haloalkyl, C3-C7 cyclohaloalkyl, C1-C7 haloalkoxy, C3-C7 cyclohaloalkoxy, C6-C 10 Aryl, 5- to 10-membered heteroaryl, CN, NR 8a R 8b , SO2R 8c , N.R. 8d SO2R 8e , NHCONR 8f is selected from the group consisting of R 8a , R 8b , R 8d , R 8g , and R 9are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl; R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 forming a heterocycle containing 3 to 7 atoms, containing a group selected from R 8c , R 8e , R 8f , and R 8h are each C1-C7 alkyl or C3-C7 cycloalkyl.

[0510] In embodiments, R 1 teeth, [ka] where: R 4a , R 4b , and y 1 According to any aspect or embodiment described herein, R 10a and R 10b are independently H, C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, SO2R 8e , COOR 8j ,CONR 8f , and C.O.R. 8h and R 10a and R 10b at least one of is selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8e , R 8f , and R 8h are each selected from the group consisting of H, C1-C7 straight chain alkyl, C3-C7 branched alkyl, and C3-C7 cycloalkyl; R 8jis C1-C7 linear alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0511] In embodiments, R 1 COOR 5 where R 5 C6~C 10 It is aryl or 5- to 10-membered heteroaryl.

[0512] In embodiments, R 1 teeth, [ka] where R 8a and R 8b are each selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl, or R 8a and R 8b optionally, together with the atoms to which they are attached, optionally oxygen, sulfur, and NR 9 and R 9 is selected from the group consisting of hydrogen, C1-C7 alkyl, and C3-C7 cycloalkyl.

[0513] In embodiments, R 1 teeth, [ka] where uu is 1 or 2.

[0514] In embodiments, R 1 teeth, [ka] where R 8jis C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0515] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0516] In embodiments, R 1 teeth, [ka] where R 8j is C1-C7 alkyl, C3-C7 cycloalkyl, C6-C 10 aryl, and 5- to 10-membered heteroaryl.

[0517] In embodiments, R 1 teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0518] In embodiments, R 1 teeth, [ka] where R 8d are independently H or unsubstituted C1-C7 alkyl, and R 8e is an unsubstituted C1-C7 alkyl.

[0519] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0520] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0521] In embodiments, R 1 teeth, [ka] where R 4a and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0522] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0523] In embodiments, R 1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0524] In embodiments, R1 teeth, [ka] where R 8h is an unsubstituted C1-C7 alkyl.

[0525] In embodiments, R 1 teeth, [ka] is.

[0526] In embodiments, R 1 teeth, [ka] is.

[0527] In embodiments, R 1 teeth, [ka] is.

[0528] In embodiments, R 1 teeth, [ka] where R 8a , R 8b , and R 8g are each independently H or unsubstituted C1-C7 alkyl, and R 8h is an unsubstituted C1-C7 alkyl.

[0529] In embodiments, R 1 teeth, [ka] is.

[0530] In embodiments, R 1 teeth, [ka] is.

[0531] In embodiments, R 1 teeth, [ka] is.

[0532] In embodiments, R 1 teeth, [ka] is.

[0533] In embodiments, R 1 teeth, [ka] is.

[0534] In embodiments, R 1 teeth, [ka] is.

[0535] In embodiments, R 1 teeth, [ka] is.

[0536] In embodiments, R 1 teeth, [ka] where R 8a and R 8b is each independently H or unsubstituted C1-C7 alkyl.

[0537] In embodiments, R 1 teeth, [ka] where R 8g are independently H or unsubstituted C1-C7 alkyl, and R 8h is independently unsubstituted C1-C7 alkyl.

[0538] In embodiments, R 1 teeth, [ka] is.

[0539] Compounds of general formulas (A) to (DDD) Further compounds of any one of general formulas (I), (I'), (I''), (II), or (III) include compounds of any one of general formulas (A)-(DDD) described herein, where any variable can be according to any aspect or embodiment described herein.

[0540] Further exemplary general formulas and compounds described herein may also include hydrates, solvates, enantiomers, diastereomers, pharmaceutically acceptable salts, and complexes thereof.

[0541] For example, in any of the general formulae described herein (e.g., any of general formulae (I) to (III) and any of general formulae (A) to (DDD)), the C5 carbon of 2-pyrrolidinone has the (R)-configuration.

[0542] Alternatively, in any of the general formulae described herein (e.g., any of general formulae (I) to (III) and any of general formulae (A) to (DDD)), the C5 carbon of 2-pyrrolidinone has the (S)-configuration.

[0543] In embodiments, provided herein are compounds having a structure according to the following general formula (A): [ka] In the formula, R a , R b , n, and alkyl are as described herein according to any aspect and embodiment of these variables, and A is any of the A groups listed herein with respect to general formulas (I)-(III). 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from.

[0544] In embodiments, provided herein are compounds having a structure according to the following general formula (B): [ka] In the formula, R a , R b , n, and aryl are as described herein according to any aspect and embodiment of these variables, and A is any of the A groups listed herein with respect to general formulas (I)-(III). 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from.

[0545] In embodiments, provided herein are compounds having a structure according to the following general formula (C): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2, and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0546] In embodiments, provided herein are compounds having a structure according to the following general formula (D): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein according to any aspect and embodiment of the variable n, and A is a group represented by the general formulas (I) to (II I) as described herein, 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0547] In embodiments, provided herein are compounds having a structure according to the following general formula (E): [ka] , where Q 1 is 1 or 2, and Q 2is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0548] In embodiments, provided herein are compounds having a structure according to the following general formula (F): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0549] In embodiments, provided herein are compounds having a structure according to the following general formula (G): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is represented by the general formula (I ) to (III), as described herein with respect to R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0550] In embodiments, provided herein are compounds having a structure according to the following general formula (H): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , RN2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0551] In embodiments, provided herein are compounds having a structure according to the following general formula (J): [ka] In the formula, Q 1 is 1 or 2, and Q 2 is 1 or 2, n is as described herein in accordance with any aspect and embodiment of the variable n, and A is any of the A 1 , A 2 , and A 3 As described in any aspect and embodiment of 1 , A 2 , and A 3 is selected from R N is as described herein with respect to general formulas (I)-(III), R N1 , R N2 , and R N3 As described in any aspect and embodiment of N1 , R N2 , and R N3 is selected from.

[0552] In certain embodiments, provided herein are compounds having a structure according to the following general formula (K): [ka] R N is C 1~ selected from the group consisting of C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; R a and R bare each selected from the group consisting of hydrogen, C1-C7 straight chain alkyl, and C3-C7 branched alkyl; R 2 is phenyl, naphthyl, pyridyl, indolyl, and [ka] and R 3 is selected from the group consisting of phenyl, naphthyl, pyridyl, and indolyl.

[0553] In certain embodiments, provided herein are compounds having a structure according to the following general formula (L): [ka] R N is C 1~ selected from the group consisting of C7 straight chain alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl; R 2 is phenyl, naphthyl, pyridyl, indolyl, and [ka] and R 3 is selected from the group consisting of phenyl, naphthyl, pyridyl, and indolyl.

[0554] In embodiments, herein: [ka] Compounds are provided that include units, wherein L A is the A described herein 1 , A 2 , and A 3 In an embodiment, L A teeth, [ka] is selected from the group consisting of:

[0555] In embodiments, provided herein are compounds having a structure according to the following general formula (M): [ka] In the formula, R 2a , a, L A ,n,R 4a , R 4b , y 1 , R 10a , and R 10b is as described with respect to any general formula, aspect, or embodiment described herein.

[0556] In embodiments, provided herein are compounds having a structure according to the following general formula (N): [ka] In the formula, R 2a ,a,n,R 4a , R 4b , y 1 , R 10a , and R 10b is as described with respect to any general formula, aspect, or embodiment described herein.

[0557] In embodiments, provided herein are compounds having a structure according to the following general formula (O): [ka] In the formula, R 2a , a, L A ,n,R 4a , R 4b , y 1 , p 1 , p 2 , and Z a is as described with respect to any general formula, aspect, or embodiment described herein.

[0558] In embodiments, provided herein are compounds having a structure according to the following general formula (P): [ka] In the formula, R 2a ,a,n,R 4a , R 4b , y 1 , p 1 , p 2 , and Z a is as described with respect to any general formula, aspect, or embodiment described herein.

[0559] In embodiments, provided herein are compounds having a structure according to the following general formula (Q): [ka] In the formula, R 2a , a, L A ,n,R 1a and X is as described with respect to any general formula, aspect, or embodiment described herein.

[0560] In embodiments, provided herein are compounds having a structure according to the following general formula (R): [ka] In the formula, R 2a ,a,n,R 1a and X is as described with respect to any general formula, aspect, or embodiment described herein.

[0561] In embodiments, provided herein are compounds having a structure according to the following general formula (S): [ka] In the formula, R 2a , a, L A , n, Y b , p 1 , p 2 , R10a , and R 10b is as described with respect to any general formula, aspect, or embodiment described herein.

[0562] In embodiments, provided herein are compounds having a structure according to the following general formula (T): [ka] In the formula, R 2a , a, n, Y b , p 1 , p 2 , R 10a , and R 10b is as described with respect to any general formula, aspect, or embodiment described herein.

[0563] In embodiments, provided herein are compounds having a structure according to the following general formula (U): [ka] In the formula, p 1 is 1, 2, 3, or 4, and R 2a , a, L A , n, p 1 , R 4b , and R 8h is as described with respect to any general formula, aspect, or embodiment described herein.

[0564] In embodiments, provided herein are compounds having a structure according to the following general formula (V): [ka] In the formula, p 1 is 1, 2, 3, or 4, and R 2a , a, n, p 1 , R 4b , and R 8h is as described with respect to any general formula, aspect, or embodiment described herein.

[0565] In embodiments, provided herein are compounds having a structure according to the following general formula (W): [ka] In the formula, R 2a , a, L A , n, y 1 , R 4a , and R 4b is as described with respect to any general formula, aspect, or embodiment described herein.

[0566] In embodiments, provided herein are compounds having a structure according to the following general formula (X): [ka] In the formula, R 2a , a, n, y 1 , R 4a , and R 4b is as described with respect to any general formula, aspect, or embodiment described herein.

[0567] In embodiments, provided herein are compounds having a structure according to the following general formula (Y): [ka] In the formula, R 5N is selected from H, C1-C7 straight chain alkyl, and C3-C7 branched alkyl, and R 2a , a, L A , n, y 1 , R 4a , and R 4b is as described with respect to any general formula, aspect, or embodiment described herein.

[0568] In embodiments, provided herein are compounds having a structure according to the following general formula (Z): [ka] In the formula, R5N is selected from H, C1-C7 straight chain alkyl, and C3-C7 branched alkyl, and R 2a , a, n, y 1 , R 4a , and R 4b is as described with respect to any general formula, aspect, or embodiment described herein.

[0569] In embodiments, provided herein are compounds having a structure according to the following general formula (AA): [ka] In the formula, R 5a is pyridyl or pyridazine, and R 2a , a, L A , and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0570] In embodiments, provided herein are compounds having a structure according to the following general formula (BB): [ka] In the formula, R 5a is pyridyl or pyridazine, and R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0571] In embodiments, provided herein are compounds having a structure according to the following general formula (CC): [ka] In the formula, R 5b is C1-C7 fluoroalkyl or C3-C7 cyclofluoroalkyl, and R 2a , a, L A , and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0572] In embodiments, provided herein are compounds having a structure according to the following general formula (DD): [ka] In the formula, R 5b is C1-C7 fluoroalkyl or C3-C7 cyclofluoroalkyl, and R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0573] In embodiments, provided herein are compounds having a structure according to the following general formula (EE): [ka] In the formula, R N is a C1-C7 alkyl, and R 5c is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 fluoroalkyl, or C3-C7 cyclofluoroalkyl, and R 2a , a, L A , and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0574] In embodiments, provided herein are compounds having a structure according to the following general formula (FF): [ka] In the formula, R N is a C1-C7 alkyl, and R 5c is C1-C7 alkyl, C3-C7 cycloalkyl, C1-C7 fluoroalkyl, or C3-C7 cyclofluoroalkyl, and R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0575] In embodiments, provided herein are compounds having a structure according to the following general formula (GG): [ka] In the formula, R 2 ,a,n,R a , and R b is as described with respect to any general formula, aspect, or embodiment described herein.

[0576] In embodiments, provided herein are compounds having a structure according to the following general formula (HH): [ka] In the formula, R 2 and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0577] In embodiments, provided herein are compounds having a structure according to the following general formula (JJ): [ka] In the formula, R 2 and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0578] In embodiments, provided herein are compounds having a structure according to the following general formula (KK): [ka] In the formula, R 2 and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0579] In embodiments, provided herein are compounds having a structure according to the following general formula (LL): [ka] In the formula, R 2and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0580] In embodiments, provided herein are compounds having a structure according to the following general formula (MM): [ka] In the formula, R 1 , R 2 and n is as described with respect to any general formula, aspect, or embodiment described herein.

[0581] In embodiments, provided herein are compounds having a structure according to the following general formula (NN): [ka] In the formula, R 1 , R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0582] In embodiments, provided herein are compounds having a structure according to the following general formula (OO): [ka] In the formula, R 1 , R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0583] In embodiments, provided herein are compounds having a structure according to the following general formula (PP): [ka] In the formula, R 1 , R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein.

[0584] In embodiments, provided herein are compounds having a structure according to the following general formula (QQ): [ka] In the formula, R 2 , n, and X are as described with respect to any general formula, aspect, or embodiment described herein.

[0585] In embodiments, provided herein are compounds having a structure according to the following general formula (RR): [ka] In the formula, R 2 ,n,R 6a , R 6b , and R 7 is as described with respect to any general formula, aspect, or embodiment described herein.

[0586] In embodiments, provided herein are compounds having a structure according to the following general formula (SS): [ka] In the formula, R 2 ,n,R 6c , R 6d , and R 7 is as described with respect to any general formula, aspect, or embodiment described herein.

[0587] In embodiments, provided herein are compounds having a structure according to the following general formula (TT): [ka] In the formula, R 8h , R 2a , R 4a , R A , R N3, a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, R 8h is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, R 4a is hydrogen or unsubstituted C1-C7 alkyl (e.g., R 4a In embodiments, n is hydrogen, methyl, ethyl, or isopropyl). In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R 4a The carbon substituted with has the (R)-configuration. 4a The carbon substituted with has the (S)-configuration. A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0588] In embodiments, provided herein are compounds having a structure according to the following general formula (UU): [ka] In the formula, R 8e , R 2a , a, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R 8e is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2aare each halogen (e.g., —F and / or —Cl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration.

[0589] In embodiments, provided herein are compounds having a structure according to the following general formula (VV): [ka] In the formula, R N3 , R 2a , R A , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H. In an embodiment, R N3 In embodiments, n is methyl. In embodiments, n is 2. In embodiments, a is 0, 1, or 2. In embodiments, a is 0. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A is a C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone skeleton has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone skeleton has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0590] In embodiments, provided herein are compounds having a structure according to the following general formula (WW): [ka] In the formula, R N3 , R 2a , R A , R 5, a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R 5 is unsubstituted C1-C7 alkyl (e.g., methyl or ethyl). N3 is H or methyl. In an embodiment, n is 2. In an embodiment, aa is 0 or 1. In an embodiment, R A is C1-C7 alkyl (e.g., methyl). In embodiments, a is 1. In embodiments, a is 0, 1, or 2. In embodiments, a is 0. In embodiments, a is 1. In embodiments, R 2a are each halogen (e.g., —F and / or —Cl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0591] In embodiments, provided herein are compounds having a structure according to the following general formula (XX): [ka] In the formula, R 5 , R A , R N3 , R 2a , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, R 5 is unsubstituted C1-C7 alkyl (e.g., methyl, ethyl, isopropyl). 5 is C1-C7 haloalkyl (e.g., CH2CF3). In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2ais a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0592] In embodiments, provided herein are compounds having a structure according to the following general formula (YY): [ka] In the formula, R A , R N3 , R 2a , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0593] In embodiments, provided herein are compounds having a structure according to the following general formula (ZZ): [ka] In the formula, R 8j , R 2a , R A , R N3 , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, R 8j is unsubstituted C1-C7 alkyl (e.g., methyl or ethyl). In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0594] In embodiments, provided herein are compounds having a structure according to the following general formula (AAA): [ka] In the formula, R A , R N3 , R 2a , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R AWhen present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0595] In embodiments, provided herein are compounds having a structure according to the following general formula (BBB): [ka] In the formula, R A , R N3 , R 2a , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 teeth, In an embodiment, n is 1 or 2. In an embodiment, a is 1. In an embodiment, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0596] In embodiments, provided herein are compounds having a structure according to the following general formula (CCC): [ka] In the formula, R 8a , R 8b , RA , R N3 , R 2a , a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, R 8a is hydrogen or unsubstituted C1-C7 alkyl (e.g., methyl). 8b is hydrogen or unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2a is a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0597] In embodiments, provided herein are compounds having a structure according to the following general formula (DDD): [ka] , where R A , R N3 , R 2a , uu, a, aa, and n are as described with respect to any general formula, aspect, or embodiment described herein. In embodiments, R N3 is H or methyl. In embodiments, uu is 1 or 2. In embodiments, n is 2. In embodiments, a is 1 or 2. In embodiments, a is 1. In embodiments, R 2ais a halogen (e.g., —F and / or —Cl). In embodiments, aa is 0 or 1. In embodiments, R A When present, is unsubstituted C1-C7 alkyl (e.g., methyl). In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (R)-configuration. In embodiments, the C5 carbon of the 2-pyrrolidinone backbone has the (S)-configuration. In embodiments, R A The carbon substituted with has the (R)-configuration. A The carbon substituted with has the (S)-configuration.

[0598] Exemplary Compounds Exemplary compounds according to the general formulas described herein (e.g., according to general formula (I), (II), or (III), e.g., any of general formulas (A)-(DDD)) include compounds A1-A209 as set forth in Table 1. Table 1: Exemplary compounds [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] [Table 1-12] [Table 1-13] [Table 1-14] [Table 1-15] [Table 1-16] [Table 1-17] [Table 1-18] [Table 1-19] [Table 1-20] [Table 1-21] [Table 1-22] [Table 1-23] [Table 1-24]

[0599] General synthetic methods for the preparation of 5-HT7 modulators The reagents used in the preparation of the compounds of the present invention can be commercially obtained or prepared by standard procedures described in the literature. In accordance with the present invention, compounds of this class can be produced by one of the following reaction schemes. Intermediates in the synthetic procedures can also be prepared according to the methods described in the entirety of the methods filed, each of which is incorporated herein by reference.

[0600] For example, exemplary methods that can be adapted to prepare the compounds described herein include those described in International Application No. PCT / US19 / 31824, as well as WO 2018 / 093818, WO 2014 / 085413, WO 2014 / 164756, WO 2016 / 040554, WO 2016 / 183150, WO 2018 / 175190, and WO 2018 / 175188, each of which is incorporated by reference in its entirety.

[0601] Certain exemplary methods are set forth in Schemes 1-13, in which the variables within any structure can be according to any aspect or embodiment described herein. Scheme 1. [ka]

[0602] A known compound or a compound prepared by a known method, which is a compound of general formula (a1), is reacted with a compound of general formula (a1a), wherein LG is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate, in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a2). Alternatively, a compound of general formula (a1) is reacted with a compound of general formula (a1a), wherein LG is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a2).

[0603] The compound of general formula (a2) is reacted with a known compound of general formula (a2a) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, or the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, or the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a3). Scheme 2. [ka]

[0604] Alternatively, a known compound of the general formula (a1) or a compound prepared by a known method can be reacted with palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium(II), In the presence of a palladium catalyst such as carbon or bis(acetonitrile)dichloropalladium(II), for example, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, (2-biphenyl)dicyclohexylphosphine, (2-biphenyl)di-tert-butylphosphine, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, sodium In the presence of an organophosphine such as 2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 2-di-tert-butylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2'-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine, 2'-(diphenylphosphino)-N,N'-dimethyl-(1,1'-biphenyl)-2-amine, optionally in the presence of, for example, sodium carbonate, lithium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide, triethylamine, N,N-di In the presence of a base such as isopropylethylamine, pyridine, 2,6-dimethylpyridine, and the like, in a solvent such as tetrahydrofuran, 1,4-dioxane, acetonitrile, methylene chloride, chloroform, 1,2-dichloroethane, 1,2-dimethoxyethane, and the like, optionally with heating and optionally with microwave irradiation, a compound of general formula (a1b), wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate, is reacted with a known compound prepared by a known method, to obtain a compound of general formula (a4).

[0605] Alternatively, a known compound of the general formula (a1) or a compound prepared by a known method can be reacted with a base such as sodium carbonate, lithium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, or the like in the presence of copper iodide in a solvent such as tetrahydrofuran, 1,4-dioxane, acetonitrile, methylene chloride, chloroform, 1,2-dichloroethane, 1,2-dimethoxyethane, or the like. with a compound of general formula (a1b), wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate, in a solvent such as ethane, N,N-dimethylformamide, N,N-dimethylacetamide, 1-methyl-2-pyrrolidinone, dimethyl sulfoxide, or the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a4).

[0606] The compound of general formula (a4) is reacted with a known compound of general formula (a4a) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, or the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, or the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a5). Scheme 3. [ka]

[0607] Compounds according to general formula (a3) ​​are reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, etc. in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, optionally with heating, optionally with microwave irradiation, to give compounds of general formula (a6). The compound of general formula (a6) may be reacted with a compound of general formula (a6) in the presence of a coupling agent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, optionally in the presence of 1-hydroxy-7-azabenzotriazole, etc. Optionally, in the presence of a base such as triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, and in the presence of a solvent such as N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, 1,2-dimethoxyethane, and the like, optionally by heating and optionally by microwave irradiation, a compound of general formula (a8) is obtained by reaction with a compound of general formula (a7). Compounds according to general formula (a8) are reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, etc. in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, optionally with heating, optionally with microwave irradiation, to give compounds of general formula (a9).

[0608] The compound of general formula (a9) is reacted with a known compound of general formula (a10) or a compound prepared by a known method in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give the compound of general formula (a10-a). Alternatively, the compound of general formula (a9) can be converted into a compound of general formula (a10-1), wherein X is a group represented by the formula (a10-1), in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation. 1is chlorine to obtain a compound of general formula (a10-b). Alternatively, the compound of general formula (a9) can be reacted with a known compound or a compound prepared by a known method, in which R is chlorine, in the presence of a coupling agent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, and optionally with 1-hydroxy-7-azabenzotriazoline. in the presence of a base such as triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, and in the presence of a solvent such as N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, 1,2-dimethoxyethane, and optionally by heating and optionally by microwave irradiation, to give a compound of general formula (a10-1), wherein X 1 is OH, to give a compound of general formula (a10b).

[0609] Alternatively, a compound of general formula (a9) can be reacted with a compound of general formula (a10-2), a known compound or a compound prepared by a known method, in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a10-c). Scheme 4. [ka]

[0610] Alternatively, the compound of general formula (a6) can be reacted with, for example, N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethylformamide, dimethylformamide, etc. in the presence of a coupling agent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, optionally in the presence of 1-hydroxy-7-azabenzotriazole, etc., and optionally in the presence of a base such as triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, etc. Reaction with a compound of general formula (a7-1) in the presence of a solvent such as sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, or 1,2-dimethoxyethane, optionally with heating and optionally with microwave irradiation, gives a compound of general formula (a8-1). Scheme 5. [ka]

[0611] The compound of general formula (a6) can be reacted with, for example, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, optionally in the presence of 1-hydroxy-7-azabenzotriazole, and optionally with, for example, triethylamine. In the presence of a base such as N,N-diisopropylethylamine, pyridine, or 2,6-dimethylpyridine, in the presence of a solvent such as N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, or 1,2-dimethoxyethane, optionally with heating and optionally with microwave irradiation, a compound of general formula (a12) is obtained. Compounds according to general formula (a12) are reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, optionally with heating, optionally with microwave irradiation, to give compounds of general formula (a13).

[0612] The compound according to the general formula (a13) can be reacted with, for example, triethylamine, diisopropyl ethyl amine,

[0047] Alternatively, the compound of general formula (a13) may be reacted with a known compound of general formula (a14) or a compound prepared by a known method in the presence of a base such as triethylamine, diisopropylethylamine, pyridine, or the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a14a). Alternatively, the compound of general formula (a13) may be reacted with a known compound of general formula (a14) or a compound prepared by a known method in the presence of a base such as triethylamine, diisopropylethylamine, pyridine, or the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a14-1), wherein X 1 is chlorine to give a compound of general formula (a14b). Alternatively, the compound of general formula (a13) can be reacted with a known compound or a compound prepared by a known method, in the presence of a coupling agent such as 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, and optionally with 1-hydroxy-7-azabenzotriazoline. in the presence of a base such as triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, and in the presence of a solvent such as N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, 1,2-dimethoxyethane, and optionally by heating and optionally by microwave irradiation, to give a compound of general formula (a14-1), wherein X1 is OH to give a compound of general formula (a14b). Alternatively, a compound of general formula (a13) is reacted with a compound of general formula (a14-2) where X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsulfonate, in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a14c). Scheme 6. [ka]

[0613] The compound of general formula (a6) can be reacted in the presence of a palladium catalyst such as palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II) to produce, for example, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, or Phenyl, (2-biphenyl)dicyclohexylphosphine, (2-biphenyl)di-tert-butylphosphine, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, sodium In the presence of an organophosphine such as 2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 2-di-tert-butylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2'-(di-tert-butylphosphino)-N,N-dimethylbiphenyl-2-amine, 2'-(diphenylphosphino)-N,N'-dimethyl-(1,1'-biphenyl)-2-amine, optionally in the presence of, for example, sodium carbonate, lithium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide, triethylamine, N,N-diphenylphosphino In the presence of a base such as isopropylethylamine, pyridine, or 2,6-dimethylpyridine, in a solvent such as tetrahydrofuran, 1,4-dioxane, acetonitrile, methylene chloride, chloroform, 1,2-dichloroethane, or 1,2-dimethoxyethane, optionally with heating and optionally with microwave irradiation, a compound of general formula (a15), wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate, is reacted with a known compound prepared by a known method, to obtain a compound of general formula (a15-1). Scheme 7. [ka]

[0614] The compound of general formula (a6) can be reacted with, for example, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N'-dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, optionally in the presence of a hydroxybenzotriazole, optionally in the presence of 1-hydroxy-7-azabenzotriazole, and optionally with, for example, triethylamine. In the presence of a base such as N,N-diisopropylethylamine, pyridine, or 2,6-dimethylpyridine, in the presence of a solvent such as N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, methylene chloride, chloroform, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, or 1,2-dimethoxyethane, optionally with heating and optionally with microwave irradiation, a compound of general formula (a17) is obtained. Scheme 8. [ka]

[0615] The compound of general formula (a6) is reacted with a known compound of general formula (a10-3) or a compound prepared by a known method in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a10-4). Scheme 9. [ka]

[0616] The compound of general formula (a6) is reacted with a known compound of general formula (a10-5) or a compound prepared by a known method in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a10-6). Scheme 10. [ka]

[0617] The compound of general formula (a6) is reacted with a known compound of general formula (a10-7) or a compound prepared by a known method in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (a10-8). Scheme 11. [ka]

[0618] The compound of general formula (a6) can be converted into a known compound, which is a compound of general formula (a10-9), in the presence of a base such as triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or acetonitrile, optionally by heating and optionally by microwave irradiation. or a compound prepared by a known method to obtain a compound of general formula (a10-10). Scheme 12. [ka]

[0619] A compound of general formula (a18), a known compound or a compound prepared by a known method, is reacted with a compound of general formula (a19), wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate and para-tolylsufonate, in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a20). Alternatively, the compound of general formula (a18) can be reacted with, for example, a palladium catalyst such as palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II). 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, (2-biphenyl)dicyclohexylphosphine, (2-biphenyl)di-tert-butylphosphine, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl, 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-1,1'-biphenyl, sodium 2'-Dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 2-di-tert-butylphosphino-2'-methylbiphenyl, 2-dicyclohexylphosphino-2'-methylbiphenyl, 2'-(di-tert-butylphosphino)-N,In the presence of an organophosphine such as N-dimethylbiphenyl-2-amine, 2'-(diphenylphosphino)-N,N'-dimethyl-(1,1'-biphenyl)-2-amine, optionally in the presence of a base such as sodium carbonate, lithium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide, potassium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine, 2,6-dimethylpyridine, for example, tetrahydrofuran, 1,4-dioxane, The compound of general formula (a20) is obtained by reacting the compound of general formula (a19) with a known compound prepared by a known method, wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsulfonate, in a solvent such as acetonitrile, methylene chloride, chloroform, 1,2-dichloroethane, or 1,2-dimethoxyethane, optionally with heating and optionally with microwave irradiation. The compound of general formula (a20) is then reacted with a known compound prepared by a known method, for example, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, hydrogenation, In the presence of a base such as potassium or lithium hydride, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, or the like, optionally with heating and optionally with microwave irradiation, a compound of general formula (a21) in which X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate is reacted to obtain a compound of general formula (a22). The compound of general formula (a22) is reacted with a compound of general formula (a23) wherein X is selected from the group consisting of iodine, bromine, chlorine, methanesulfonate, and para-tolylsufonate in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, or isopropanol, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (a24). Scheme 13. [ka]

[0620] The compound of general formula (a24) is reacted with an acid such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and / or microwave irradiation, to obtain a compound of general formula (a25). Alternatively, the compound of general formula (a24) is reacted with tetrabutylammonium fluoride in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and / or microwave irradiation, to obtain a compound of general formula (a25). The compound of general formula (a25) is reacted with 4-methylbenzenesulfonyl chloride in the presence of a base such as triethylamine, N,N-diisopropylethylamine, pyridine, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, optionally with heating, optionally with microwave irradiation, and optionally in the presence of 4-dimethylaminopyridine to give a compound of general formula (a26). The compound of general formula (a26) is reacted with a known compound of general formula (a27) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, or the like, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, or the like, optionally with heating and optionally with microwave irradiation. This gives a compound of general formula (a28).

[0621] Still further exemplary syntheses are provided herein. One of ordinary skill in the art would be able to synthesize N-substituted pyrrolidine compounds (e.g., R N These syntheses can be readily adapted for the preparation of still further compounds of the invention, including the preparation of compounds according to any of the general formulae described herein where is not hydrogen.

[0622] Compounds of the present disclosure may be prepared according to the methods outlined in the following schemes. Scheme 14. [ka]

[0623] A known compound or a compound prepared by a known method, which is a suitably substituted compound of general formula (1), wherein PG is a protecting group selected from the group consisting of benzyl, tert-butyl carbonate, benzyl carbonate, and tert-butyldimethylsilyl, is reacted with a known compound of general formula (2), or a compound prepared by a known method, in the presence of BnNEt3Cl in the presence of a base, such as potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium hydroxide, and in the presence of a solvent, such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, methanol, ethanol, isopropanol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (3). The compound of general formula (3) is converted into a compound of general formula (4), Z, in the presence of a base such as pyridine, 2,6-dimethylpyridine, 2,6-di-tert-butylpyridine, triethylamine, diisopropylethylamine, or the like, in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, or the like, optionally by heating and optionally by microwave irradiation.1 is reacted with a known compound or a compound prepared by known methods, wherein the aryl group is selected from the group consisting of methyl, trifluoromethyl, para-tolyl, and para-NO2-phenyl, to obtain a compound of general formula (5). The compound of general formula (5) is reacted with a base, such as potassium carbonate, sodium carbonate, cesium carbonate, or lithium carbonate, in a solvent, such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (6). Scheme 15. [ka]

[0624] The compound of general formula (6) is reacted with a known compound or a compound prepared by a known method, which is a compound of general formula (7), in the presence of a base such as, for example, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (8). The compound of general formula (8) is reacted with an acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, para-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and the like in a solvent such as benzene, toluene, para-xylylene, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and the like, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (9). The compound of general formula (9) is reacted with a compound of general formula (10), a known compound or a compound prepared by a known method, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, in the presence of a base such as, for example, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (11). Scheme 16. [ka]

[0625] Compounds of general formula (11) are reacted with sodium in the presence of naphthalene in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to give compounds of general formula (12). Compounds of general formula (12) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide, optionally with heating, to give compounds of general formula (13). Alternatively, a compound of general formula (12) can be reacted with an acid, such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid, in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and / or microwave irradiation, to obtain a compound of general formula (13). Alternatively, a compound of general formula (12) can be reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and / or microwave irradiation, to obtain a compound of general formula (13). Reaction with carbon tetrabromide in the presence of methyl phosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, gives compounds of general formula (14). The compound of general formula (14) is reacted with a known compound of general formula (15) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (16). Scheme 17. [ka]

[0626] Alternatively, a compound of general formula (6) is reacted with a known compound of general formula (17) or a compound prepared by a known method in the presence of a base such as, for example, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride in a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (18). The compound of general formula (18) is reacted with an acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, para-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and the like in a solvent such as benzene, toluene, para-xylylene, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and the like, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (19). The compound of general formula (19) is reacted with a compound of general formula (20), a known compound or a compound prepared by a known method, wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, in the presence of a base such as, for example, lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (21).The compound of general formula (21) can be converted into a compound of general formula (22) in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation. ) where LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, to obtain a compound of general formula (11). Scheme 18. [ka]

[0627] Compounds of general formula (19) can be reacted in the presence of a base, such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent, such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to produce compounds of general formula (23), in which LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, and in which Q 1is reacted with a known compound or a compound prepared by known methods selected from the group consisting of 1 and 2 to obtain a compound of general formula (24). The compound of general formula (24) is reacted with a compound of general formula (25), wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, in the presence of a base such as lithium diisopropylamide, sodium diisopropylamide, potassium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, sodium hydride, potassium hydride, or lithium hydride, in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (25), wherein LG is selected from the group consisting of bromine, chlorine, methanesulfonate, and para-tolylsufonate, and wherein Q 2is reacted with a known compound or a compound prepared by known methods selected from the group consisting of 1 and 2 to give a compound of general formula (26). The compound of general formula (26) can be reacted with, for example, benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium, (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium, dichloro(2-isopropoxyphenylmethylene)ruthenium, or the like in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide, optionally by heating and optionally by microwave irradiation, to produce a compound such as benzylidene-bis(tricyclohexylphosphine)dichlororuthenium, (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium, (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium, or dichloro(2-isopropoxyphenylmethylene)ruthenium. (phenylmethylene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)bis(3-bromopyridine)ruthenium (II), dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2-butenylidene)(tricyclohexylphosphine)ruthenium(II), dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), [1,3-dimesityl-2-imidazolidinylidene] dichloro[3-(2-pyridinyl)propylidene]ruthenium(II), dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II), dichloro(tricyclohexylphosphine)[(tricyclohexylphosphoranyl)methylidene]ruthenium tetrafluoroborate, dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(tricyclohexylphosphoranyl)methylidene]ruthenium(II) tetrafluoroborate, [2-(1-methylethoxy-O)phenylmethyl-C](nitrato-O,O'){rel-(2R,5R,7R)-azathiol The compound of general formula (27) is obtained by reacting with a ruthenium catalyst such as damantane-2,1-diyl[3-(2,4,6-trimethylphenyl)-1-imidazolidinyl-2-ylidene]}ruthenium, dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II), [1,3-bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium(II), or dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][3-(2-pyridinyl)propylidene]ruthenium(II). Scheme 19. [ka]

[0628] Compounds of general formula (27) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of general formula (28). Compounds of general formula (28) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of general formula (29). Alternatively, a compound of general formula (28) can be reacted with an acid such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (29). Alternatively, a compound of general formula (28) can be reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and optionally with microwave irradiation, to obtain a compound of general formula (29). The compound of general formula (29) is reacted with, for example, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,2-diene in the presence of naphthalene. Reaction with sodium in a solvent such as ethanol, optionally with heating and optionally with microwave irradiation, provides compounds of general formula (30). Scheme 20. [ka]

[0629] Alternatively, compounds of general formula (27) can be reacted with sodium in the presence of naphthalene in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and optionally with microwave irradiation, to provide compounds of general formula (31). Compounds of general formula (31) can be reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide, optionally with heating, to provide compounds of general formula (32). Compounds of general formula (32) are reacted with hydrogen gas in the presence of a palladium catalyst, such as, for example, palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as, for example, methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of general formula (30). Alternatively, compounds of general formula (32) can be reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, and the like in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to provide compounds of general formula (30).Alternatively, compounds of general formula (32) are reacted with tetrabutylammonium fluoride in the presence of a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, optionally with heating, and optionally with microwave irradiation, to provide compounds of general formula (30). Scheme 21. [ka]

[0630] The compound of formula (30) is reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to give compounds of formula (33 The compound of general formula (33) is reacted with a known compound of general formula (34) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, or pyridine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, or isopropanol, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (35). Scheme 22. [ka]

[0631] Compounds of general formula (31) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of general formula (36). Alternatively, a compound of general formula (31) can be reacted with an acid, such as trifluoroacetic acid, hydrochloric acid, or sulfuric acid, in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (36). Alternatively, a compound of general formula (31) can be reacted with tetrabutylammonium fluoride in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (36). Compounds of formula (36) are reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to give compounds of formula (37).The compound of general formula (37) is reacted with a known compound of general formula (38) or a compound prepared by a known method in the presence of a base such as sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (39). Scheme 23. [ka]

[0632] A compound of general formula (26) is reacted with a compound of general formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating, which may be by microwave irradiation. The resulting material is then treated with triphenylphosphine in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating, which may be by microwave irradiation, to provide a compound of general formula (40). Alternatively, a compound of general formula (26) is reacted with a compound of general formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating, which may be by microwave irradiation. The resulting material is then treated with dimethyl sulfide in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating, which may be by microwave irradiation, to provide a compound of general formula (40). Alternatively, compounds of general formula (26) are reacted with ruthenium chloride in the presence of sodium periodate in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water, and optionally with heating, which may be by microwave irradiation, to provide compounds of general formula (40).Alternatively, compounds of general formula (26) can be reacted with potassium osmate dehydrate in the presence of potassium ferricyanide, optionally in the presence of potassium carbonate, optionally in the presence of a base such as potassium hydroxide, sodium hydroxide, lithium hydroxide, and in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, acetone, ethyl acetate, benzene, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water, and optionally by heating, which may be by microwave irradiation, to give compounds of general formula (40). Alternatively, a compound of general formula (26) can be reacted with osmium tetroxide in the presence of sodium periodate in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, acetone, ethyl acetate, benzene, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, optionally in the presence of a base such as pyridine, 2,6-lutidine, 2,6-di-tert-butylpyridine, optionally in the presence of water, optionally with heating, and optionally with microwave irradiation, to give a compound of general formula (40). Alternatively, the compound of general formula (26) may be optionally heated in the presence of N-methylmorpholine N-oxide in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, acetone, ethyl acetate, benzenetoluene, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water. with osmium tetroxide, optionally with microwave irradiation, to give a compound of general formula (40). Compounds of general formula (40) are reacted with benzylamine in the presence of a reducing agent, such as sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, lithium borohydride, lithium triacetoxyborohydride, or lithium cyanoborohydride, in the presence of a solvent, such as methylene chloride, 1,2-dichloroethane, methanol, ethanol, isopropanol, tert-butanol, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, benzene, toluene, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating and optionally with microwave irradiation, to give a compound of general formula (41). The compound of general formula (41) is reacted with hydrogen gas in the presence of a palladium catalyst such as palladium on carbon, palladium barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II) in an organic solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, or N,N-dimethylformamide to obtain a compound of general formula (42). Scheme 24. [ka]

[0633] Compounds of general formula (42) are reacted with di-tert-butyl dicarbonate in the presence of a base such as pyridine, 2,6-lutidine, triethylamine, or diisopropylethylamine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, methanol, ethanol, or isopropanol, optionally with heating and / or microwave irradiation, to give compounds of general formula (43). Compounds of general formula (43) are reacted with sodium in the presence of naphthalene in a solvent such as tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, or 1,2-diethoxyethane, optionally with heating and / or microwave irradiation, to give compounds of general formula (44). Compounds of general formula (44) are reacted with hydrogen gas in the presence of a palladium catalyst, such as palladium on carbon, palladium on barium sulfate, palladium(II) acetate, tetrakis(triphenylphosphine)palladium(0), dichlorobis(triphenylphosphine)palladium(II), palladium on carbon, or bis(acetonitrile)dichloropalladium(II), in an organic solvent, such as methanol, ethanol, ethyl acetate, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, 1,2-dichloroethane, N,N-dimethylformamide, and the like, optionally with heating, to provide compounds of general formula (45). Alternatively, compounds of general formula (44) can be reacted with an acid such as trifluoroacetic acid, hydrochloric acid, sulfuric acid, and the like in a solvent such as tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to provide compounds of general formula (45).Alternatively, compounds of general formula (44) are reacted with tetrabutylammonium fluoride in the presence of a solvent such as, for example, tetrahydrofuran, 1,4-dioxane, methylene chloride, 1,2-dichloroethane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, optionally with heating, and optionally with microwave irradiation, to provide compounds of general formula (45). Scheme 25. [ka]

[0634] Compounds of formula (45) are reacted with carbon tetrabromide in the presence of triphenylphosphine in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating and optionally with microwave irradiation, to give compounds of formula (46). A compound of general formula (46) is reacted with a known compound of general formula (47) or a compound prepared by a known method in the presence of a base such as, for example, sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, triethylamine, diisopropylethylamine, pyridine, and the like in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (48). Compounds of general formula (48) are reacted with an acid such as trifluoroacetic acid, formic acid, acetic acid, hydrochloric acid, sulfuric acid, and the like, optionally in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, isopropanol, and the like, optionally with heating and optionally with microwave irradiation, to provide compounds of general formula (49). Scheme 26. [ka]

[0635] The compound of general formula (49) is reacted with a known compound or a compound prepared by known methods, which is a compound of general formula (50), in the presence of a base such as, for example, triethylamine, diisopropylethylamine, pyridine, in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, optionally with heating, optionally with microwave irradiation, to provide a compound of general formula (51). Scheme 27. [ka]

[0636] Reaction of a compound of general formula (49) with a known compound or a compound prepared by known methods, which is a compound of general formula (52), in the presence of a base such as, for example, triethylamine, diisopropylethylamine, pyridine, in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, optionally with heating, optionally with microwave irradiation, provides a compound of general formula (53). Scheme 28. [ka]

[0637] Reaction of a compound of general formula (49) with a known compound or a compound prepared by known methods, which is a compound of general formula (54), in the presence of a base such as, for example, triethylamine, diisopropylethylamine, pyridine, in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, optionally with heating, optionally with microwave irradiation, provides a compound of general formula (55). Scheme 29. [ka]

[0638] Reaction of a compound of general formula (49) with a known compound or a compound prepared by known methods, which is a compound of general formula (56), in the presence of a base such as, for example, triethylamine, diisopropylethylamine, pyridine, in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, optionally with heating, optionally with microwave irradiation, provides a compound of general formula (57). Scheme 30. [ka]

[0639] The compound of general formula (49) is reacted with a known compound or a compound prepared by known methods, which is a compound of general formula (58), in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, and the like, optionally with heating and optionally with microwave irradiation, to provide a compound of general formula (59). Scheme 31. [ka]

[0640] The compound of general formula (49) is reacted with a known compound or a compound prepared by known methods, which is a compound of general formula (60), in the presence of a base such as, for example, triethylamine, diisopropylethylamine, pyridine, in a solvent such as, for example, methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, optionally with heating, optionally with microwave irradiation, to give a compound of general formula (61). Scheme 32. [ka]

[0641] A compound of general formula (62) is reacted with a compound of general formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating, which may be by microwave irradiation. The resulting material is then treated with triphenylphosphine in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating, which may be by microwave irradiation, to give a compound of general formula (63). Alternatively, a compound of general formula (62) can be reacted with a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, or N,N-dimethylacetamide, optionally with heating, which may be by microwave irradiation. The resulting material is then treated with dimethyl sulfide in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, or the like, optionally with heating, which may be by microwave irradiation, to give a compound of general formula (63). Alternatively, compounds of general formula (62) are reacted with ruthenium chloride in the presence of sodium periodate in a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water, and optionally with heating, which may be by microwave irradiation, to provide compounds of general formula (63). Alternatively, compounds of general formula (62) can be reacted with potassium osmate dehydrate in the presence of potassium ferricyanide, optionally in the presence of potassium carbonate, optionally in the presence of a base such as potassium hydroxide, sodium hydroxide, lithium hydroxide, and in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, acetone, ethyl acetate, benzene, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water, and optionally by heating, which may be by microwave irradiation, to provide compounds of general formula (63).Alternatively, a compound of general formula (62) can be reacted with osmium tetroxide in the presence of sodium periodate in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, acetone, ethyl acetate, benzene, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, optionally in the presence of a base such as pyridine, 2,6-lutidine, 2,6-di-tert-butylpyridine, optionally in the presence of water, optionally with heating, and optionally with microwave irradiation to give a compound of general formula (63). Alternatively, compounds of general formula (62) can be reacted with osmium tetroxide in the presence of N-methylmorpholine N-oxide in the presence of a solvent such as methanol, ethanol, isopropanol, tert-butanol, 1,4-dioxane, tetrahydrofuran, 1,2-dimethoxyethane, acetone, ethyl acetate, benzene, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally in the presence of water, optionally with heating, and optionally with microwave irradiation, to give compounds of general formula (63). Scheme 33. [ka]

[0642] The compound of general formula (64) is reacted with a compound of general formula ozone in the presence of a solvent such as methylene chloride, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, methanol, ethanol, 1,2-dimethoxyethane, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, optionally with heating, which may be by microwave irradiation. The resulting material is then reacted with a solvent such as methylen...

Claims

1. A compound having a structure according to general formula (I") or a pharmaceutically acceptable salt thereof: 【Chemical 691】 During the ceremony, R aa and R bb are each selected from the group consisting of hydrogen, C 1 -C 7 alkyl, and C 3 -C 7 branched alkyl; R N1' is hydrogen or C 1 -C 7 alkyl; Each R AA is independently a C 1 -C 7 straight chain alkyl; each R 2a is independently halogen, unsubstituted C 1 -C 7 alkyl, C 1 -C 7 perhaloalkyl, unsubstituted C 1 -C 7 alkoxy, C 1 -C 7 perhaloalkoxy, or CN; a is 1 or 2; aa is 0, 1, or 2, and wherein when R N1′ is hydrogen, aa is 1 or 2, or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1, wherein R N1′ is C 1 -C 7 alkyl.

3. The compound of claim 1, wherein R aa and R bb are each ethyl.

4. The compound described in claim 1, wherein aa is 0 or 1.

5. The compound of claim 1, wherein aa is 1 or 2, and each R AA is methyl.

6. The compound of claim 1, wherein each R 2a is independently halogen.

7. The compound of claim 6, wherein each R 2a is independently —F or —Cl.

8. The compound of claim 1, wherein the C5 carbon of the 2-pyrrolidinone has an (R)-configuration.

9. The compound of claim 1, wherein the C5 carbon of the 2-pyrrolidinone has an (S)-configuration.

10. 【Chemical 692】 【Chemical Formula 693】 【Chemical Formula 694】 1. A compound selected from the group consisting of: or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 11, further comprising at least one pharmaceutically acceptable excipient.

13. A composition comprising a compound described in any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described in claim 11 or 12, for treating a disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity.

14. The disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity is a peripherally selective disease, a nervous system disease, a circadian rhythm disorder, depression, schizophrenia, neurogenic inflammation, hypertension, peripheral vascular disease, migraine, neuropathic pain, peripheral pain, allodynia, thermoregulatory disorders, learning disabilities, memory disorders, hippocampal signaling disorders, sleep disorders, attention deficit / hyperactivity disorder, anxiety disorders, avoidant personality disorder, premature ejaculation, eating disorders, premenstrual syndrome, premenstrual dysphonia, 14. The composition of claim 13, wherein the therapeutic agent is selected from the group consisting of: inflammatory bowel disease (IBD), seasonal affective disorder, bipolar disorder, inflammatory bowel disease (IBD), enteritis, epilepsy, seizure disorders, drug addiction, alcohol addiction, breast cancer, liver fibrosis, chronic liver injury, hepatocellular carcinoma, small intestinal neuroendocrine tumors, and lung injury.

15. The composition described in claim 14, wherein the disease associated with dysregulation of 5-hydroxytryptamine receptor 7 activity is inflammatory bowel disease (IBD) or enteritis.

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