Deuterated tryptamine derivatives and methods of use

Abstract

To provide a composition for use in the treatment of neuropsychiatric diseases or disorders, or inflammatory diseases or disorders.SOLUTION: An injectable composition comprising a compound according to formula (III-b) and a liquid pharmaceutically acceptable vehicle, or an optically pure stereoisomer, pharmaceutically acceptable salt, or solvate thereof. (Wherein R2, R6 and R7 are hydrogen, R8 is deuterated methyl or ethyl, R9 is hydrogen, deuterium or the like.) SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates generally to compounds, and in some embodiments, to compounds that inhibit serotonin 5-HT2 receptors. agonists and their use in the treatment of diseases associated with the 5-HT2 receptor. [Background technology]

[0002] Serotonin 5-HT2 receptors (5-HT2Rs) contain 5-HT 2A , 5-HT 2B , and 5-HT 2C There are three closely related subtypes of lysergic acid LSD, psilocybin, and 2,5-dimethoxy-4-bromoamphetamine They are the primary target of classical serotonergic hallucinogens such as diazepam (DOB). They share 60% transmembrane amino acid homology, which means they share one subtype more frequently than other subtypes. This poses the challenge of designing molecules with selectivity for each subtype. They are expressed and stimulated in specific patterns in animals (both peripheral tissues and the central nervous system). These hormones produce unique biochemical, physiological, and behavioral effects. 2A Activation of Rs primarily mediates hallucinogenic effects and causes anti-inflammatory effects, whereas 5-HT2 C Activation of Rs reduces feeding behavior. However, 5-HT 2B Chronic activity of Rs Activation is associated with valvular heart disease (VHD), a life-threatening adverse event (AE). In addition, 5-HT 2A Patients who may benefit from medication experience hallucinatory effects There are also concerns that there may be resistance to this.

[0003] Tryptamines are a class of serotonergic hallucinogens that act on serotonin 5-HT2Rs They have very high potency (in some cases, sub-nanomolar affinity). Tammin is a 5-HT 2B Rs and 5-HT 2C 5-HT than Rs 2A Selection against Rs Its selectivity—in some cases 100-fold—makes it superior to typical hallucinogens and other serotonin receptors. They are distinguished from psychedelic hallucinogens.

[0004] AEs caused by tryptamines and other serotonergic hallucinogens are comparatively associated with high-dose intake of 5-HT 2A Rs and 5-HT 2C Non at Rs. Due to their consistently high potency, the active oral dose of tryptamines is extremely low. BOMe(2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) (phenyl)methyl)ethan-1-amine) is orally active at doses as low as 25 μg and is non- The consistently strong hallucinogenic doses are in the 500-700 μg range. Misuse or abuse of these or higher doses can cause visual and auditory hallucinations, excitement, and aggression. It can cause shock and psychosis, and intoxication can lead to toxicity (e.g., rhabdomyolysis) and Furthermore, tryptamine can undergo extensive first-pass metabolism. , and is orally inactive.

[0005] 5-HT 2B Serotonin 5-HT overcomes the R problem and hallucinogenic effects 2A R Agoni The need for new drugs and the need to improve their bioavailability and enhance oral activity It is important to have a drug that does not produce neurologically toxic (e.g., psychotomimetic) plasma concentrations; There is a further need for effective, more convenient, and controllable tryptamine formulations. Summary of the Invention

[0006] The present disclosure provides methods for identifying compounds that modulate the serotonin 5-HT2 receptor and for administering serotonin 5 - at least in part, in a method for using it to treat a disease associated with the HT2 receptor More specifically, the present disclosure provides a method for producing hallucinogenic effects, for example, by administering once a day. Without 5-HT 2A Selective engagement of Rs and neuropsychiatric and inflammatory The present invention provides novel compounds that enable the treatment of rheumatoid arthritis and other disorders related to rheumatoid arthritis.

[0007] Without being bound to any particular theory, selective The novel compounds described herein with suitable deuteration may provide improved exposure (i.e., Significant delay in enzymatic degradation due to prevention of acute high drug concentration (spike) observed after administration and increased blood / brain ratio, which is thought to result in improved oral bioavailability Some compounds described herein can be prepared by selective deuteration of the phenyl ring to give similar Bring profit.

[0008] As used herein, the compounds of formula (III) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0009] In some embodiments, X1 and X2 are deuterium.

[0010] In some embodiments, Y 1 and Y 2 are hydrogen or deuterium.

[0011] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0012] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0013] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0014] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0015] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0016] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0017] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0018] In some embodiments, when R4 is hydroxyl, R9 is hydrogen.

[0019] In some embodiments, when R4 is hydroxyl, R9 is deuterium.

[0020] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0021] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0022] In some embodiments, the compound of formula (III) has formula (III-a), as described below: Formula (III-b), Formula (III-c), Formula (III-d), Formula (III-e), Formula (II If), formula (III-g), formula (III-h), formula (III-i), formula (III-j) , formula (III-k), formula (III-l), formula (III-m), formula (III-n), formula (I II-o), Formula (III-p), Formula (III-q), Formula (III-r), Formula (III-s ), formula (III-t), formula (III-u), formula (III-v).

[0023] As used herein, the compound according to formula (III-a) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0024] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0025] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0026] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0027] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0028] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0029] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0030] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0031] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium.

[0032] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0033] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0034] As used herein, the compound according to formula (III-b) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0035] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0036] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0037] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0038] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0039] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R9 are not unsubstituted methyl.

[0040] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0041] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0042] As used herein, the compound according to formula (III-c) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0043] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0044] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0045] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0046] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0047] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0048] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0049] As used herein, the compounds according to formula (III-d) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0050] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0051] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0052] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0053] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0054] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R 9 are both -CD3.

[0055] In some embodiments, R9 is hydrogen.

[0056] In some embodiments, R9 is hydrogen or deuterium.

[0057] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0058] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0059] As used herein, the compounds according to formula (III-e) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0060] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0061] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0062] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0063] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0064] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0065] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0066] As used herein, the compounds of formula (III-f) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0067] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0068] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0069] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0070] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0071] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0072] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0073] As used herein, the compound according to formula (III-g) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0074] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0075] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0076] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0077] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0078] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0079] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0080] As used herein, the compounds of formula (III-h) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0081] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0082] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0083] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0084] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0085] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0086] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0087] As used herein, the compounds according to formula (III-i) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0088] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0089] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0090] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0091] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0092] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0093] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0094] As used herein, the compound according to formula (III-j) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0095] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0096] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0097] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0098] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0099] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0100] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0101] As used herein, the compounds of formula (III-k) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0102] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or selected from substituted aryl, and unsubstituted or substituted heteroaryl;

[0103] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0104] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0105] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0106] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0107] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0108] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0109] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. .

[0110] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0111] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0112] As used herein, the compounds according to formula (III-1) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0113] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0114] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0115] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0116] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0117] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R9 are not unsubstituted methyl.

[0118] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0119] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0120] As used herein, the compounds of formula (III-m) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0121] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0122] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0123] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0124] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0125] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0126] As used herein, the compounds of formula (III-n) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0127] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0128] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0129] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0130] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0131] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R 9 are both -CD3.

[0132] In some embodiments, R9 is hydrogen.

[0133] In some embodiments, R9 is deuterium.

[0134] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0135] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0136] As used herein, the compounds of formula (III-o) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0137] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0138] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0139] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0140] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0141] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0142] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0143] As used herein, the compounds of formula (III-p) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0144] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0145] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0146] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0147] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0148] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0149] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0150] As used herein, the compounds of formula (III-q) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0151] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0152] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0153] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0154] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0155] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0156] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0157] As used herein, the compounds of formula (III-r) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0158] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0159] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. ,

[0160] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0161] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0162] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0163] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0164] As used herein, the compounds of formula (III-s) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0165] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0166] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0167] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0168] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0169] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0170] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0171] As used herein, the compounds of formula (III-t) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0172] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0173] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0174] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0175] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0176] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0177] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0178] As used herein, the compounds of formula (III-u) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0179] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0180] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0181] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0182] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0183] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0184] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0185] As used herein, the compounds according to formula (III-v) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0186] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0187] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0188] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0189] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0190] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0191] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0192] In some embodiments, the compound is: [ka] [ka] [ka] [ka]

[0193] In some embodiments, the compound has the structure: [ka]

[0194] In some embodiments, the compound is an agonist of the serotonin 5-HT2 receptor.

[0195] In some embodiments, the compound is serotonin 5-HT 2A may be an agonist of the receptor do.

[0196] Pharmaceutical compositions comprising the compounds disclosed herein and a pharmaceutically acceptable vehicle are also disclosed herein. Disclosed in the specification.

[0197] Also disclosed are methods for treating a disease or condition comprising administering to a subject a therapeutically effective amount of a compound disclosed herein. Disclosed herein are methods for treating a subject having a steroid or disorder.

[0198] Also disclosed are methods for treating a disease or condition comprising administering to a subject a therapeutically effective amount of a compound disclosed herein. Disclosed herein are methods for treating a subject having a steroid or disorder.

[0199] Also disclosed are methods for treating serotonin, including administering to a subject a therapeutically effective amount of a compound disclosed herein. Methods for treating a subject having a disease or disorder associated with the 5-HT2 receptor are described herein. In some embodiments, the compound has the structure: [ka]

[0200] In some embodiments, the disease or disorder is, for example, post-traumatic stress disorder (PTSD). ), major depressive disorder (MDD), treatment-resistant depression (TRD), suicidal ideation, suicidal behavior, Major depressive disorder with homicidal ideation or suicidal behavior, non-suicidal self-injury disorder (NSSID), bipolar disorder, and related disorders (including, but not limited to, bipolar I disorder, bipolar II disorder, and cyclothymic disorder) Obsessive-Compulsive Disorder (OCD), Generalized Anxiety Disorder (GAD), Social Anxiety Disorder, Substance Abuse Use disorders (alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder) use disorder, and cocaine use disorder), anorexia nervosa Alzheimer's disease, cluster headaches and migraines, attention deficit hyperactivity disorder (ADHD), DHD), pain and neuropathic pain, aphantasia, childhood-onset dysphagia, significant neurocognitive disorders Central nervous system (CNS) disorders such as intellectual disability, mild neurocognitive impairment, sexual dysfunction, and obesity In some embodiments, the disease or disorder is alcohol use disorder. In some embodiments, the disease or disorder may involve a condition of the autonomic nervous system (ANS). In embodiments, the disease or disorder is a pulmonary disorder (e.g., asthma and chronic obstructive pulmonary disorder (COPD)). In some embodiments, the disease or disorder may include cardiovascular disorders (e.g., atherosclerosis, pulmonary embolism, pulmonary edema ... This may include rheumatoid arteriosclerosis.

[0201] Also, treating subjects with alcohol use disorders associated with the serotonin 5-HT2 receptor. 1. A method for treating a cancer, comprising administering to a subject a therapeutically effective amount of a compound having the structure: A method is disclosed. [ka]

[0202] As used herein, trimethoprim-containing compounds such as DMT, 5-MeO-DMT, psilocybin, and psilocin are used. or any of the compounds described herein, or a pharmaceutically acceptable salt thereof. Also disclosed is a single-layer orally administered tablet composition comprising a tolerable salt and a polymer. In the form, the compound has the following structure: [ka]

[0203] In some embodiments, the composition is adapted for maximum sustained release.

[0204] In some embodiments, the tablet composition comprises: (i) a water-insoluble, neutrally charged non-ionic matrix; (ii) a polymer bearing one or more negatively charged groups, and (iii) DMT, 5-MeO - tryptamine derivatives such as DMT, psilocybin, and psilocin, or any of the compounds described herein The present invention includes combinations of any of the compounds listed above, or pharmaceutically acceptable salts thereof.

[0205] In some embodiments, the non-ionic matrix is ​​a cellulosic polymer alone or Starch, wax, neutral rubber, polymethacrylate, PVA, PVA / PVP blend, or mixtures thereof. is selected from

[0206] In some embodiments, the cellulosic polymer is hydroxypropyl methylcellulose. (HPMC).

[0207] In some embodiments, the polymer carrying one or more negatively charged groups is polyacrylic acid, poly(ethylene glycol). Polylactic acid, polyglycolic acid, polymethacrylate carboxylate, cation exchange resin, Clay, zeolite, hyaluronic acid, anionic gums, their salts, or mixtures thereof is.

[0208] In some embodiments, the anionic rubber may be a natural material, a semi-synthetic material, or a combination thereof. It is a combination.

[0209] In some embodiments, the natural materials include alginic acid, pectin, xanthan gum, and caramel. Geenan, locust bean gum, gum arabic, karaya gum, guar gum, tragacanth rubber, or a combination thereof.

[0210] In some embodiments, the semi-synthetic material is carboxymethyl-chitin, cellulose gum, or or a combination thereof.

[0211] In some embodiments, the tablet composition comprises DMT, 5-MeO-DM1 for the treatment of pain. Tryptamine derivatives such as T, psilocybin, and psilocin, or any of the compounds described herein The present invention includes a therapeutically effective amount of any of the compounds listed above, or a pharmaceutically acceptable salt thereof.

[0212] In some embodiments, the tablet composition comprises a compound selected from the group consisting of DMT, 5-MeO-D, and 5-MeO-D for the treatment of brain injury. Tryptamine derivatives such as MT, psilocybin, and psilocin, or any of the compounds described herein The present invention includes a therapeutically effective amount of any of the compounds described above, or a pharmaceutically acceptable salt thereof.

[0213] In some embodiments, the tablet composition comprises DMT, 5-MeO-D Tryptamine derivatives such as MT, psilocybin, and psilocin, or any of the compounds described herein The present invention includes a therapeutically effective amount of any of the compounds described above, or a pharmaceutically acceptable salt thereof.

[0214] In some embodiments, the tablet composition is used to treat a disease or condition associated with the serotonin 5-HT2 receptor. is seeking approval of DMT, 5-MeO-DMT, psilocybin, and psilocybin for use in the treatment of psychotropic psychosis. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or and a therapeutically effective amount of a pharmaceutically acceptable salt thereof.

[0215] In some embodiments, the disease or disorder is major depressive disorder (MDD), suicidal ideation or Major depressive disorder with suicidal behavior (MDD), suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSI) SSID), Treatment-Resistant Depression (TRD), Post-Traumatic Stress Disorder (PTSD), Bipolar Bipolar and related disorders, including bipolar I disorder, bipolar II disorder, and cyclothymic disorder; obsessive-compulsive disorder (OCD); CD), generalized anxiety disorder (GAD), social anxiety disorder, alcohol use disorder, opioids substance use disorder, including use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headaches and migraines, Attention-deficit hyperactivity disorder (ADHD), pain and neuropathic pain, aphantasia, childhood onset Fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, leukemia from the group consisting of central nervous system (CNS) disorders, including rheumatoid arthritis, obesity, or a combination thereof. In some embodiments, the disease or disorder is an alcohol use disorder.

[0216] In some embodiments, the disease or disorder comprises a condition of the autonomic nervous system (ANS).

[0217] In some embodiments, the disease or disorder includes asthma and chronic obstructive pulmonary disorder (COPD). Including lung disorders.

[0218] In some embodiments, the disease or disorder is a cardiovascular disorder, including atherosclerosis. include.

[0219] In some embodiments, the composition comprises DMT, 5-MeO-DMT, psilocybin, psilocin or any of the compounds described herein, or The combined concentration of the pharmaceutically acceptable salt is adjusted to 10 to 500 (e.g., about 10, 20, 3 0, 40, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500 ng / ml or more (or, for example, about 100 to about 300 ng / ml , about 10 to about 250 ng / ml, or about 50 to about 400 ng / ml, The concentration is achieved in the range of 500 ng / ml (any range of 500 ng / ml) and maintained at this concentration for the duration of the release period.

[0220] In some embodiments, the polymer comprises one or more negatively charged groups.

[0221] Also, tryptamines such as DMT, 5-MeO-DMT, psilocybin, and psilocin Derivatives, or any of the compounds described herein, or pharmaceutically acceptable derivatives thereof Disclosed herein is a tablet composition formulated for oral administration, comprising a salt and a polymer. In some embodiments, the compound has the structure: [ka]

[0222] In some embodiments, the polymer comprises one or more negatively charged groups.

[0223] In some embodiments, the polymer comprises one or more acid groups.

[0224] In some embodiments, the polymer comprises a water-insoluble, neutrally charged non-ionic matrix.

[0225] In some embodiments, the non-ionic matrix is ​​a cellulosic polymer alone or Starch, wax, neutral rubber, polymethacrylate, PVA, PVA / PVP blend, or mixtures thereof. is selected from

[0226] In some embodiments, the cellulosic polymer is hydroxypropyl methylcellulose. (HPMC).

[0227] Also described herein are: 1) the monolayer orally administered tablet compositions disclosed herein; and 2) a kit for treating a subject, the kit including instructions for use in treating pain. is.

[0228] Also described herein are: 1) the monolayer orally administered tablet compositions disclosed herein; and 2) a kit for treating the subject, including instructions for use in treating brain injury. It is.

[0229] Also described herein are: 1) the monolayer orally administered tablet compositions disclosed herein; and 2) a kit for treating the subject, including instructions for use in treating depression. It is.

[0230] Also described herein are: 1) the monolayer orally administered tablet compositions disclosed herein; and 2) use in treating diseases or disorders associated with the serotonin 5-HT2 receptor. and instructions for administering the compound to a subject. DETAILED DESCRIPTION OF THE INVENTION

[0231] The following detailed description of the embodiments of the present disclosure provides a thorough understanding of the embodiments of the present disclosure. For purposes of illustration, numerous specific details are set forth. However, it should be understood that the embodiments of the present disclosure may be modified in various ways without departing from the spirit and scope of the present invention. It will be apparent to one skilled in the art that the present invention may be practiced without these specific details. It is to be understood that well-known methods, procedures, and components may be used interchangeably to avoid unnecessarily obscuring aspects of the embodiments of the present disclosure. , and the circuit is not described in detail.

[0232] Unless otherwise defined, all technical and scientific terms used herein are understood to be within the meaning of the present disclosure. It has the same meaning as commonly understood by a person skilled in the art to which it pertains.

[0233] "Alkyl" refers to an alkyl group having, for example, 1 to 6 carbon atoms, or 1 to 5, or 1 to 4, or is a monovalent saturated aliphatic hydrocarbon having 1 to 10 carbon atoms, such as 1 to 3 carbon atoms. This term refers to the alkyl group. Examples include methyl (CH3-), ethyl (CH3CH2-) and methyl (CH3CH2-). ), n-propyl (CH3CH2CH2-), isopropyl ((CH3)2CH-), n -butyl (CH3CH2CH2CH2-), isobutyl ((CH3)2CHCH2-), sec-butyl ((CH3)(CH3CH2)CH-), t-butyl ((CH3)3C- ), n-pentyl (CH3CH2CH2CH2CH2-), and neopentyl ((CH 3) 3CCH2-) and other linear and branched hydrocarbyl groups.

[0234] The term "substituted alkyl" refers to an alkyl group, as defined herein, having a substituent in the alkyl chain. One or more carbon atoms may optionally be -O-, -N-, -S-, -S(O) n -(n is 0 to 2 -NR- (where R is hydrogen or alkyl), or Alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl aryl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, aminoacyl aryl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxy aryl, oxo, thioketo, carboxyl, carboxyl alkyl, thio aryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thio alkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, hetero aryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxy -amino, nitro, -SO-alkyl, -SO-aryl, -SO-heteroaryl, - SO2-alkyl, -SO2-aryl, -SO 2- Heteroaryl, and -NR a R b , where R ’ and R ’ ’ may be the same or different and are hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, 1 to 5 groups selected from the group consisting of heteroaryl and heterocyclic groups It has a substituent.

[0235] "Alkylene" is -O-, -NR 10 -, -NR 10 C(O)-, -C(O)NR 1 0 -, optionally interrupted by one or more groups selected from a divalent aliphatic hydrocarbyl group having 1 to 6 carbon atoms, including 1 to 3 carbon atoms, This term includes, by way of example, methylene (-CH2-), ethylene (-CH2CH2- ), n-propylene (-CH2CH2CH2-), iso-propylene (-CH2CH(C H3)-), (-C(CH3)2CH2CH2-), (-C(CH3)2CH2C(O) -), (-C(CH3)2CH2C(O)NH-), (-CH(CH3)CH2-), etc. Includes:

[0236] "Substituted alkylene" refers to a group that is substituted as described for carbon in the definition of "substituted" below. It refers to an alkylene group having 1 to 3 hydrogen atoms substituted with a group.

[0237] The term "alkane" refers to alkyl and alkylene groups as defined herein.

[0238] The terms "alkylaminoalkyl," "alkylaminoalkenyl," and "alkyl "Aminoalkynyl" is R ’ NHR ” - refers to the group R ’ is an alkyl group as defined herein. is a methyl group, R ” is alkylene, alkenylene, or alkynylene as defined herein. It is a hydroxyl group.

[0239] The term "alkaryl" or "aralkyl" refers to alkylene, substituted alkylene, and aralkyl. -alkylene-aryl and -substituted alkylene-aryl, where aryl is defined herein. It refers to the alkyl group.

[0240] "Alkoxy" refers to an -O-alkyl group, where alkyl is as defined herein. Examples of alkoxy include methoxy, ethoxy, n-propoxy, isopropoxy, and the like. oxy, n-butoxy, t-butoxy, sec-butoxy, n-pentoxy, etc. The term "alkoxy" also includes alkenyl-O-, cycloalkyl-O-, cycloalkane ... It refers to the groups alkenyl, cycloalkyl, cycloalkyl-O-, and alkynyl-O-. Alkenyl, and alkynyl are as defined herein.

[0241] The term "substituted alkoxy" refers to substituted alkyl-O-, substituted alkenyl-O-, substituted cyclo ... It refers to alkyl-O-, substituted cycloalkenyl-O-, and substituted alkynyl-O- groups. , substituted alkyl, substituted alkenyl, substituted cycloalkyl, substituted cycloalkenyl, and Substituted alkynyl is as defined herein.

[0242] The term "alkoxyamino" refers to the group -NH-alkoxy, where alkoxy is as defined herein. As defined.

[0243] The term "haloalkoxy" refers to an alkyl-O- group in which one or more hydrogen atoms on the alkyl group have been removed. An atom is substituted with a halo group, examples of which include groups such as trifluoromethoxy.

[0244] The term "haloalkyl" refers to an alkyl group substituted as described above, One or more hydrogen atoms are replaced with a halo group. Examples of such groups include trifluoro Fluoroalkyl groups such as methyl, difluoromethyl, and trifluoroethyl are included. However, the present invention is not limited to these.

[0245] The term "alkylalkoxy" refers to -alkylene-O-alkyl, alkylene-O-substituted Alkyl, substituted alkylene-O-alkyl, and substituted alkylene-O-substituted alkyl The groups alkyl, substituted alkyl, alkylene, and substituted alkylene are used herein to refer to the groups alkyl, substituted alkyl, alkylene, and substituted alkylene. As defined.

[0246] The term "alkylthioalkoxy" refers to an -alkylene-S-alkyl group, an alkylene-S -substituted alkyl groups, substituted alkylene-S-alkyl groups, and substituted alkylene-S-substituted groups The term "alkyl" refers to an alkyl group, and alkyl, substituted alkyl, alkylene, and substituted alkylene are used herein. As defined in the Subsection.

[0247] "Alkenyl" has 2 to 6 carbon atoms, such as 2 to 4 carbon atoms, e.g., A straight or branched hydrocarbon having at least one, such as one or two, double bond unsaturation sites. This term refers to the aryl group. Examples of such groups include bivinyl, allyl, and but-3-ene- The term includes cis and trans isomers, or derivatives thereof. It includes a mixture of

[0248] The term "substituted alkenyl" includes alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, and substituted cycloalkyl. alkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyl Oxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl , azide, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carbo oxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy oxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, hydroxy Heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxy dimethylamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -S O-aryl, -SO-heteroaryl, -SO2-alkyl, -SO2-substituted alkyl , -SO2-aryl and -SO2-heteroaryl; or an alkenyl group, as defined herein, having one to three substituents.

[0249] "Alkynyl" has 2 to 6 carbon atoms, such as 2 to 3 carbon atoms, e.g., A straight or branched monovalent alkyl group having at least one, e.g., one or two, triple bond unsaturation sites. Examples of such alkynyl groups include acetylenyl (-C≡CH). and propargyl (-CHC≡CH).

[0250] The term "substituted alkynyl" includes alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, and substituted cycloalkyl. alkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyl Oxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl , azide, cyano, halogen, hydroxyl, oxo, thioketo, carboxyl, carbo oxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy oxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, hydroxy Heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxy dimethylamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -S O-aryl, -SO-heteroaryl, -SO2-alkyl, -SO2-substituted alkyl , -SO2-aryl and -SO2-heteroaryl; or an alkynyl group, as defined herein, bearing one to three substituents.

[0251] "Alkynyloxy" refers to the group -O-alkynyl, where alkynyl is defined herein. Examples of alkynyloxy include ethynyloxy, propynyloxy, and the like. This includes shi, etc.

[0252] "Acyl" refers to the HC(O)- group, alkyl-C(O)- group, substituted alkyl-C(O)- group, - group, alkenyl-C(O)- group, substituted alkenyl-C(O)- group, alkynyl-C(O )- group, substituted alkynyl-C(O)- group, cycloalkyl-C(O)- group, substituted cycloalkynyl-C(O)- group, alkyl-C(O)- group, cycloalkenyl-C(O)- group, substituted cycloalkenyl-C( O)- group, aryl-C(O)- group, substituted aryl-C(O)- group, heteroaryl-C(O)- group (O)- group, substituted heteroaryl-C(O)- group, heterocyclyl-C(O)- group, and and substituted heterocyclyl-C(O)- groups, including alkyl, substituted alkyl, alkenyl, and substituted heterocyclyl-C(O)- groups. Substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkyl cycloalkenyl, substituted cycloalkenyl, aryl, substituted aryl, heteroaryl, Substituted heteroaryl, heterocyclic, and substituted heterocyclic are as defined herein. For example, acyl contains the "acetyl" group CH3C(O).

[0253] "Acylamino" is -NR 20 C(O) alkyl group, -NR 20 C(O) substituted alkyl NR 20 C(O)cycloalkyl group, -NR 20C(O)-substituted cycloalkyl groups, -NR 20 C(O) cycloalkenyl group, -NR 20 C(O)-substituted cycloalkenyl groups, -NR 20 C(O) alkenyl group, -NR 20 C(O)-substituted alkenyl group, -NR 20 C (O) Alkynyl group, -NR 20 C(O)-substituted alkynyl group, -NR 20 C(O) Ally -NR 20 C(O) substituted aryl group, -NR 20 C(O) heteroaryl group, -N R 20 C(O)-substituted heteroaryl groups, -NR 20 C(O) heterocyclic groups, and -NR 2 0 C(O)-substituted heterocyclic groups, R 20 is hydrogen or alkyl, and alkyl, Substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkenyl alkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, substituted Aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are included herein. As defined in the Subsection.

[0254] "Aminocarbonyl" or the term "aminoacyl" refers to -C(O)NR 21 R 22 The base Point, R 21 and R 22 are independently hydrogen, alkyl, substituted alkyl, alkenyl, Substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl , substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroaryl, R is selected from the group consisting of substituted heteroaryl, heterocyclic, and substituted heterocyclic; 21 Oh BiR 22 optionally, together with the nitrogen attached thereto, form a heterocyclic or substituted heterocyclic group; and alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted Substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloa alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are as defined herein.

[0255] "Aminocarbonylamino" is -NR 21 C(O)NR 22 R 23 R refers to the group 2 1 , R 22 , and R 23 are independently hydrogen, alkyl, aryl, or cycloalkyl. and two R groups are joined to form a heterocyclyl group.

[0256] The term "alkoxycarbonylamino" refers to the group -NRC(O)OR, where each R is independently and hydrogen, alkyl, substituted alkyl, aryl, heteroaryl, or heterocyclyl. and alkyl, substituted alkyl, aryl, heteroaryl, and heterocyclyl are As defined herein.

[0257] The term "acyloxy" refers to an alkyl-C(O)O- group, a substituted alkyl-C(O)O- group , cycloalkyl-C(O)O- group, substituted cycloalkyl-C(O)O- group, aryl- C(O)O- group, heteroaryl-C(O)O- group, and heterocyclyl-C(O)O - refers to the group alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl , heteroaryl, and heterocyclyl are as defined herein.

[0258] "Aminosulfonyl" is -SO2NR 21 R 22 R refers to the group 21 and R 22 is German In particular, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted Substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, cyclo alkenyl, substituted cycloalkenyl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic rings, R 21 and R 22 is optional and the nitrogen bonded to it and the alkyl, substituted ... alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, Substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, substituted aryl , heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic are defined herein. As it is justified.

[0259] "Sulfonylamino" is -NR 21 SO2R 22 R refers to the group 21 and R 22 is German In particular, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted Substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, cyclo alkenyl, substituted cycloalkenyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic, R21 and R 22 is optional, and optionally bonded together with the adjacent atoms to form a heterocyclic or substituted heterocyclic group, and , substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkenyl alkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, Substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are included herein. As defined in the specification.

[0260] "Aryl" or "ar" refers to a single ring (such as in a phenyl group) or If the point of attachment is through an atom of an aromatic ring, the fused ring may or may not be aromatic. ring systems having multiple fused rings (examples of such aromatic ring systems include naphthyl, anthryl, and refers to a monovalent aromatic carbocyclic group of 6 to 18 carbon atoms having a carbon atom selected from the group consisting of aryl, ... and indanyl. This term includes, by way of example, phenyl and naphthyl. Definition of Aryl Substituents Unless restricted by the above, such aryl groups may be acyloxy, hydroxy, thiol, , acyl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, Substituted cycloalkenyl, amino, substituted amino, aminoacyl, acylamino, alkaryl , aryl, aryloxy, azido, carboxyl, carboxyl alkyl, cyano, Halogen, nitro, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclo Chloroxy, aminoacyloxy, oxyacylamide, thioalkoxy, substituted thioalkenyl Koxy, thioaryloxy, thioheteroaryloxy, -SO-alkyl, -SO- Substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO2-alkyl, -S O2-substituted alkyl, -SO2-aryl, -SO2-heteroaryl and trihalome and optionally substituted with 1 to 5 substituents, or 1 to 3 substituents selected from methyl, do.

[0261] "Aryloxy" refers to the group -O-aryl, where aryl is defined herein. As such, includes, for example, phenoxy, naphthoxy, and the like, as also defined herein. Includes optionally substituted aryl groups.

[0262] "Amino" refers to the group NH2.

[0263] The term "substituted amino" refers to the group -NRR, where at least one R is not hydrogen. Each R is independently hydrogen, alkyl, substituted alkyl, cycloalkyl, or substituted cycloalkyl. , alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl , substituted alkynyl, aryl, heteroaryl, and heterocyclyl; It is selected.

[0264] The term "azido" refers to the group -N3.

[0265] "Carboxyl", "carboxy" or "carboxylate" refers to -CO2H or It refers to the salt.

[0266] "Carboxyl-ester" or "carboxy-ester" or the term "carbo "Oxyalkyl" or "carboxylalkyl" refers to a -C(O)O-alkyl group, -C (O)O-substituted alkyl group, -C(O)O-alkenyl group, -C(O)O-substituted alkenyl group -C(O)O-alkynyl group, -C(O)O-substituted alkynyl group, -C(O)O- ...alkynyl group, -C(O)O-alkynyl group, -C(O)O-alkynyl group, -C( Aryl group, -C(O)O-substituted aryl group, -C(O)O-cycloalkyl group, -C(O )O-substituted cycloalkyl groups, -C(O)O-cycloalkenyl groups, -C(O)O-substituted Cycloalkenyl group, -C(O)O-heteroaryl group, -C(O)O-substituted heteroaryl group -C(O)O-heterocyclic groups, -C(O)O-heterocyclic groups, and -C(O)O-substituted heterocyclic groups. aryl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cyclo Alkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, Substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are As defined herein.

[0267] "(Carboxyl-ester)oxy" or "carbonate" is -OC(O)O -alkyl group, -O-C(O)O-substituted alkyl group, -OC(O)O-alkenyl group, -OC(O)O-substituted alkenyl group, -OC(O)O-alkynyl group, -OC(O )O-substituted alkynyl group, -OC(O)O-aryl group, -OC(O)O-substituted aryl group -OC(O)O-cycloalkyl group, -OC(O)O-substituted cycloalkyl group, -OC(O)O-cycloalkenyl group, -OC(O)O-substituted cycloalkenyl group group, -O-C(O)O-heteroaryl group, -OC(O)O-substituted heteroaryl group, -OC(O)O- heterocyclic group and -OC(O)O- substituted heterocyclic group, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl , substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic is as defined herein.

[0268] "Cyano" or "nitrile" refers to the group --CN.

[0269] "Cycloalkyl" refers to a group consisting of single or multiple cyclic rings, including fused, bridged, and spiro ring systems. Examples of suitable cycloalkyl groups include: Examples of such aryl groups include adamantyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclopropyl. Such cycloalkyl groups include, for example, cyclopropyl, octyl, and the like. single ring structures such as cyclobutyl, cyclopentyl, cyclooctyl, or adamantane This includes multiple ring structures such as cyclohexane and cyclohexane.

[0270] The term "substituted cycloalkyl" refers to alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, Acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyl hydroxyl, oxyaminoacyl, azido, cyano, halogen, hydroxyl, oxo, thio Oketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryl thioloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, Heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkyl , -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO 2- Al Kill, -SO2- Substituted alkyl, -SO2-aryl and -SO2-heteroaryl It refers to a cycloalkyl group having 1 to 5 substituents or 1 to 3 substituents selected from the following: vinegar.

[0271] "Cycloalkenyl" refers to a group having a single or multiple rings, e.g., 1 to 2 double bonds. A non-aromatic cyclic alkyl group having 3 to 10 carbon atoms and at least one double bond Refers to...

[0272] The term "substituted cycloalkenyl" includes alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkenyl, and substituted cycloalkenyl. substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, Acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyamino Acyl, azido, cyano, halogen, hydroxyl, keto, thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclyl oxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy , heteroaryl, heteroaryloxy, heterocyclyl, heterocyclooxy, hydro alkoxyamino, alkoxyamino, nitro, -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO 2- Alkyl, -SO 2- Substituted Al 1 to 5 substituents selected from alkyl, -SO2-aryl and -SO2-heteroaryl; It refers to a substituted group or a cycloalkenyl group having 1 to 3 substituents.

[0273] "Cycloalkynyl" refers to a group having one or more rings and at least one triple bond. It refers to a non-aromatic cycloalkyl group having 5 to 10 carbon atoms.

[0274] "Cycloalkoxy" refers to -O-cycloalkyl.

[0275] "Cycloalkenyloxy" refers to -O-cycloalkenyl.

[0276] "Halo" or "halogen" refers to fluoro, chloro, bromo, and iodo.

[0277] "Hydroxy" or "hydroxyl" refers to the group --OH.

[0278] "Heteroaryl" refers to an alkyl group having 1 to 15 carbon atoms, such as 1 to 10 carbon atoms, and an aryl group having 1 to 15 carbon atoms within the ring. an aromatic group of 1 to 10 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; Such heteroaryl groups refer to groups containing a single ring within the ring system (e.g., pyridinyl, imidazoline, or furyl), or may have multiple condensed rings (e.g., indolizinyl , quinolinyl, benzofuran, benzimidazolyl, or benzothienyl groups. wherein at least one ring in the ring system is aromatic and the point of attachment is through an atom of the aromatic ring; In some embodiments, at least one ring in the ring system is aromatic. The nitrogen and / or sulfur ring atoms of the alkyl group may be optionally oxidized to give N-oxide (N→O), This term includes, for example, pyridinyl, sulfinyl, or sulfonyl moieties. Heteroaryl groups include aryl, pyrrolyl, indolyl, thiophenyl, and furanyl. Unless constrained by the definition of the substituent, such heteroaryl groups include acyloxy, hydroxy, hydroxy, thiol, acyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkenyl alkyl, cycloalkenyl, substituted alkyl, substituted alkoxy, substituted alkenyl, substituted alkenyl quinyl, substituted cycloalkyl, substituted cycloalkenyl, amino, substituted amino, aminoacid aryl, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxylalkyl, cyano, halogen, nitro, heteroaryl, heteroaryloxy , heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamide, Thioalkoxy, substituted thioalkoxy, thioaryloxy, thioheteroaryloxy , -SO-alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl Le, -SO 2- Alkyl, -SO 2- Substituted alkyl, -SO2-aryl and -SO2 - 1 to 5 substituents selected from heteroaryl and trihalomethyl, or 1 to 3 It can be optionally substituted with one or more substituents.

[0279] The term "heteroaralkyl" refers to the group alkylene-heteroaryl, and heteroaryl are defined herein. This term includes, by way of example, pyridylmethyl, Examples include pyridylethyl, indolylmethyl, and the like.

[0280] "Heteroaryloxy" refers to -O-heteroaryl.

[0281] "Heterocycle", "heterocyclic", "heterocycloalkyl", and "heterocyclyl" are , having a single ring or multiple condensed rings, including fused bridges and spiro ring systems, and having 1 to 10 hydroxyl groups. It refers to a saturated or unsaturated group having 3 to 20 ring atoms, including the teratom. is selected from the group consisting of nitrogen, sulfur, or oxygen, and in fused ring systems, the point of attachment is non-aromatic. If via a ring, one or more of the rings may be cycloalkyl, aryl, or heteroaryl. In certain embodiments, the nitrogen and / or sulfur atoms of the heterocyclic group can be any Optionally, it is oxidized to provide an N-oxide, -S(O)-, or -SO2- moiety.

[0282] Examples of heterocycles and heteroaryls include, but are not limited to, azetidine, Pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, Indolizine, isoindole, indole, dihydroindole, indazole, purine quinolizine, isoquinoline, quinoline, phthalazine, naphthylpyridine, quinoxalin quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridinium amine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, Phenoxazine, phenothiazine, imidazolidine, imidazoline, piperidine, pipera Dinylene, indoline, phthalimide, 1,2,3,4-tetrahydroisoquinoline, 4,5 ,6,7-tetrahydrobenzo[b]thiophene, thiazole, thiazolidine, thiophene benzo[b]thiophene, morpholinyl, thiomorpholinyl (also known as thiamorpholinyl) (also called), 1,1-dioxothiomorpholinyl, piperidinyl, pyrrolidine, tetrahydrofuran Drofranil and others are included.

[0283] Unless constrained by the definition of a heterocyclic substituent, such heterocyclic groups include alkoxy, Substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted alkyl aryl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, amino Acyloxy, oxyaminoacyl, azide, cyano, halogen, hydroxyl, oxo , thioketo, carboxyl, carboxylalkyl, thioaryloxy, thioheteroa Aryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl aryl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, -SO-alkoxy alkyl, -SO-substituted alkyl, -SO-aryl, -SO-heteroaryl, -SO 2- Alkyl, -SO 2- Substituted alkyl, -SO2-aryl, -SO2-heteroaryl and and fused heterocycles, or 1 to 5 substituents, or 1 to 3 substituents, optionally substituted can be exchanged.

[0284] "Heterocyclyloxy" refers to the group --O-heterocyclyl.

[0285] The term "heterocyclylthio" refers to the group heterocyclic -S-.

[0286] The term "heterocyclene" refers to a dicyclic ring formed from a heterocycle, as defined herein. Refers to the dicarboxylic group.

[0287] The term "hydroxyamino" refers to the group --NHOH.

[0288] "Nitro" refers to the NO2 group.

[0289] "Oxo" refers to the (=O) atom.

[0290] "Sulfonyl" refers to an SO2 alkyl group, an SO2-substituted alkyl group, or a SO 2- Alkenyl group, SO2-substituted alkenyl group, SO 2- Cycloalkyl groups, SO2-substituted cycloalkyl groups Group, SO 2-Cycloalkenyl groups, SO2-substituted cycloalkenyl groups, SO 2- Aryl group, SO2-substituted aryl group, SO 2- Heteroaryl groups, SO2-substituted heteroaryl Group, SO 2- Heterocyclic groups and SO2-substituted heterocyclic groups, including alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, substituted aryl, Heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are defined herein. Examples of sulfonyl include methyl-SO2-, phenyl-SO2 -, and 4-methylphenyl-SO2-.

[0291] "Sulfonyloxy" refers to an OSO2 alkyl group, an OSO2-substituted alkyl group, an OSO2 - Alkenyl group, OSO2-substituted alkenyl group, OSO 2- Cycloalkyl groups, OSO2 Substituted cycloalkyl groups, OSO 2- Cycloalkenyl group, OSO2-substituted cycloalkenyl group, OSO 2- Aryl group, OSO2-substituted aryl group, OSO 2- Heteroaryl Groups , OSO2-substituted heteroaryl group, OSO 2- Heterocyclic groups and OSO2-substituted heterocyclic groups It refers to a cyclic group, and includes alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, and substituted alkyl groups. Substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloa alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are as defined herein.

[0292] The term "aminocarbonyloxy" refers to a group in which each R is independently hydrogen, alkyl, substituted alkyl, or substituted alkyl. , aryl, heteroaryl, or heterocyclic, and alkyl, substituted alkyl, aryl -OC(O) wherein aryl, heteroaryl, and heterocyclic are as defined herein; ) refers to the NRR group.

[0293] "Thiol" refers to the group --SH.

[0294] The term "thioxo" or "thioketo" refers to the atom (=S).

[0295] The term "alkylthio" or "thioalkoxy" refers to an -S-alkyl group, In certain embodiments, sulfur is oxidized to —S(O)—. Sulfoxides may exist as one or more stereoisomers.

[0296] The term "substituted thioalkoxy" refers to an --S-substituted alkyl group.

[0297] The term "thioaryloxy" refers to the group aryl-S-, where aryl is as defined herein. As defined, it includes optionally substituted aryl groups as defined herein.

[0298] The term "thioheteroaryloxy" refers to the group -S-heteroaryl, The aryl group is as defined herein and optionally substituted aryl, as defined herein. Contains a group.

[0299] The term "thioheterocyclooxy" refers to the group -S-heterocyclyl, The group is as defined herein, optionally substituted heterocycle as defined herein. Contains an alkyl group.

[0300] In addition to the disclosure herein, when used to modify a particular group or radical, The term "substituted" also refers to the situation where one or more hydrogen atoms of a particular group or radical are substituted with each other. is meant to be independently substituted with the same or different substituents as defined below. It is possible.

[0301] In addition to the groups disclosed for each individual term herein, the saturated groups in a particular group or radical may also be Substituents to replace one or more hydrogens on a saturated carbon atom (any two hydrogens on a single carbon) The elements are =O and =NR 70 , =N-OR 70 , which can be replaced by =N2 or =S) , unless otherwise specified, ‐R 60 , halo, =O, -OR 70 , ‐SR 70 , ‐NR 80 R 80 , trihalomethyl, -CN, -OCN, -SCN, -NO, -NO2, =N2, - N3, ‐SO2R 70 , ‐SO2O-M + , -SO2OR 70 , ‐OSO2R 70 , -O SO2O-M + , -OSO2OR 70 , -P(O)(O-)2(M + )2, -P(O)( OR 70 )OM + , -P(O)(OR 70 )2, ‐C(O)R 70 , ‐C(S)R 70 , -C(NR 70 )R 70 , ‐C(O)OM + , -C(O)OR 70 , -C(S)OR 70 , -C(O)NR 80 R80 , -C(NR 70 )NR 80 R 80 , ‐OC(O)R 7 0 , ‐OC(S)R 70 , ‐OC(O)O‐M + , -OC(O)OR 70 , -OC(S) OR 70 , ‐NR 70 C(O)R 70 , ‐NR 70 C(S)R 70 , ‐NR 70 CO2- M + , ‐NR 70 CO2R 70 , -NR 70 C(S)OR 70 , ‐NR 70 C(O)NR 80 R 80 , ‐NR 70 C(NR 70 )R 70 and -NR 70 C(NR 70 )NR 80 R 80 and R 60 is an optionally substituted alkyl group, cycloalkyl group, heteroalkyl group, alkyl groups, heterocycloalkylalkyl groups, cycloalkylalkyl groups, aryl groups, a heteroaryl group, a heteroarylalkyl group, and a heteroarylalkyl group; Each R 70 are independently hydrogen or R 60 and each R 80 are independent, R 70 Also Alternatively, two R taken together with the nitrogen atom to which they are attached 80’ 5, 6 or a 7-membered heterocycloalkyl, optionally consisting of O, N, and S and N is -H or may have C1-C3 alkyl substitution, and each M + is a carboxyl group with a net single positive charge Each M + are independently, e.g., K + , Na + , Li + Alka such as Lyon, + N(R 60 )4, or ammonium ions such as [Ca 2+ 〕 0.5 , [ Mg 2+ 〕 0.5 , or [Ba 2+ 〕 0.5 Alkaline earth ions such as (subscript 0. 5 is a compound in which one of the counter ions of the divalent alkaline earth ion is the ion of the compound of the present disclosure. The ionized form may be a chloride or other ionized compound such as the two ionized compounds disclosed herein. Typical counterions of the divalent alkaline earth ions are: or the doubly ionized compounds disclosed herein can serve such a purpose. This means that the cation can act as a counter ion to the valent alkaline earth ion. ) A specific example is -NR 80 R 80 is -NH2, -NH-alkyl, N-pyrrolidinyl, N-piperazinyl, 4N-methyl-piperazin-1-yl and N- It is intended to include morpholinyl.

[0302] In addition to the disclosure herein, "substituted" alkenes, alkynes, aryls and heteroaryls are also Substituents for hydrogen on unsaturated carbon atoms in aryl groups are -R, unless otherwise specified. 60 , Halo, -O - M+ 、‐OR 70 、‐SR 70 、-S - M + 、‐NR 80 R 80 、トリハロ メチル、-CF3、‐CN、‐OCN、‐SCN、-NO、‐NO2、‐N3、‐SO2 R 70 、‐SO3 - M + 、-SO3R 70 、‐OSO2R 70 、-OSO3 - M + 、-O SO3R 70 、-PO3 -2 (M + )2、-P(O)(OR 70 )O - M + 、-P(O) (OR 70 )2、-C(O)R 70 、-C(S)R 70 、-C(NR 70 )R 70 、-C O2 - M + 、-CO2R 70 、-C(S)OR 70 、-C(O)NR 80 R 80 、-C( NR 70 )NR 80 R 80 、-OC(O)R 70 、-OC(S)R 70 、-OCO2 - M + 、-OCO2R 70 、‐OC(S)R 70 、‐NR 70 C(O)R 70 、‐NR 70 C (S)R 70 、‐NR 70 CO2 - M + 、‐NR 70 CO2R 70, -NR 70 C(S) OR 70 , ‐NR 70 C(O)NR 80 R 80 , ‐NR 70 C(NR 70 )R 70 and -NR 70 C(NR 70 )NR 80 R 80 and R 60 , R 70 , R 80 and M + teeth , as previously defined, except that in the case of a substituted alkene or alkyne, the substituents are -O - M + , -OR 70 , ‐SR 70 , or -S - M + isn't it.

[0303] In addition to the groups disclosed for each individual term herein, "substituted" heteroalkyl groups are also The hydrogen substituents on a nitrogen in cycloheteroalkyl and cycloalkyl groups are, unless otherwise specified, -R 60 , -OM + , -OR 70 , -SR 70 , -SM + , -NR 80 R 80 , Tori Halomethyl, -CF3, -CN, -NO, -NO2, -S(O)2R 70 , -S(O)2 OM + , -S(O)2OR 70 , -OS(O)2R 70 , -OS(O)2O-M + ,- OS(O)2OR 70 , -P(O)(O-)2(M + )2, -P(O)(OR 70 )O- M +, -P(O)(OR 70 )(OR 70 ), -C(O)R 70 , -C(S)R 70 ,- C(NR 70 )R 70 , -C(O)OR 70 , -C(S)OR 70 , -C(O)NR 80 R 80 , -C(NR 70 )NR 80 R 80 , -OC(O)R 70 , -OC(S)R 70 , -OC(O)OR 70 , -OC(S)OR 70 , -NR 70 C(O)R 70 , -NR 70 C(S)R 70 , -NR 70 C(O)OR 70 , -NR 70 C(S)OR 70 , -NR 7 0 C(O)NR 80 R 80 , -NR 70 C(NR 70 )R 70 and -NR 70 C(NR 70 )NR 80 R 80 and R 60, R 70 , R 80 and M + is a previously defined That's right.

[0304] Further to the disclosure herein, in certain embodiments, the substituted group may be 1, 2, 3, or 4 substituents, 1, 2, or 3 substituents, 1 or 2 substituents, or 1 substituent It has.

[0305] Any of the above defined substituents may be defined to have further substituents attached thereto. This is achieved by defining the aryl group as a substituent group (e.g., a substituent group that is itself substituted with a substituted aryl group). a substituted aryl having a substituted aryl group as the aryl group, which is further It is understood that polymers (substituted, etc.) are not intended for inclusion herein. In such cases, the maximum number of such substitutions is three. For example, The successive substitution of substituted aryl groups is limited to substituted aryl-(substituted aryl)-substituted aryl. will be done.

[0306] Unless otherwise indicated, the naming of substituents not expressly defined herein is indicative of the functional group This is achieved by naming the terminal portion of the For example, the substituent "arylalkyloxycarbonyl" is (aryl)-( It refers to the -OC(O)- group.

[0307] It is understood that any of the groups disclosed herein that contain one or more substituents However, such groups may be used in conjunction with any sterically infeasible and / or synthetically infeasible group. It is understood that the subject compounds do not include substitutions or substitution patterns. All stereochemical isomers arising from the substitution of the compounds are included.

[0308] The term "pharmaceutically acceptable salt" refers to a compound that is acceptable to a mammal (e.g., a mammalian species) for a given administration regimen. A salt acceptable for administration to a patient, such as a salt having a counter ion that is mammalian safe. Such salts are derived from pharmaceutically acceptable inorganic or organic bases and A "pharmaceutically acceptable salt" can be obtained from a pharmaceutically acceptable inorganic or organic acid. The term "aromatic" refers to pharmaceutically acceptable salts of the compound of the formula (I), which salts include a variety of organic and inorganic salts well known in the art. Derived from counter ions, by way of example only, sodium, potassium, calcium , magnesium, ammonium, tetraalkylammonium, etc., and the molecule is basic If it contains a functional group, for example, hydrochloride, hydrobromide, formate, tartrate, besylate, mesylate, These include salts of organic or inorganic acids such as phosphates, acetates, maleates, oxalates, and the like.

[0309] The term "salt thereof" refers to a compound in which the proton of an acid is bonded to a cation, such as a metal cation or an organic cation. Where applicable, salts are pharmaceutically acceptable salts. Although acceptable salts are acceptable salts, this is not required for salts of intermediate compounds that are not intended for administration to patients. By way of example, salts of the present compounds include those in which the compounds are protonated with an inorganic or organic acid. to form a cation and a conjugate of an inorganic or organic acid as the anionic component of the salt. These include those having a base.

[0310] A "solvate" is a compound formed by the combination of solvent molecules with solute molecules or ions. The solvent can be an organic compound, an inorganic compound, or a mixture of both. Some examples of solvents include, but are not limited to, methanol, N,N-dimethylformamide, Examples of solvents include methyl amide, tetrahydrofuran, dimethyl sulfoxide, and water. When water is present, the solvate formed is a hydrate.

[0311] "Stereoisomer" and "stereoisomers" are groups of atoms that have the same atom connectivity but are different in space. Stereoisomers include cis-trans isomers, E and C isomers, and This includes A and Z isomers, enantiomers, and diastereomers.

[0312] "Tautomers" refer to tautomers that are different only in the electronic bonding of atoms and / or in enol-keto and and alternative forms of molecules that differ in the position of the protons, such as imine-enamine tautomers; or pyrazole, imidazole, benzimidazole, triazole, and tetrazole refers to tautomeric forms of heteroaryl groups containing the -N=C(H)-NH- ring atom configuration, such as One skilled in the art will recognize that other tautomeric ring atom arrangements are possible.

[0313] The term "or a salt or solvate or stereoisomer thereof" refers to a stereoisomeric form of the subject compound. All configurations of salts, solvates and stereoisomers thereof, including pharmaceutically acceptable salt solvates of the compound. It will be understood that the term "interchangeable" is intended to include interchangeable terms.

[0314] As used herein, the term "maximum sustained release" refers to increasing the release period to a maximum value. This describes the release window of certain formulations of the present disclosure formulated as follows: The digestive tract is restricted by the time it naturally expels all of the drug with food.

[0315] The term "tamper-resistant" refers to the extraction for intravenous use or the crushing for free base use. Aspects of a drug formulation that make it more difficult to use the formulation to abuse the drug portion of the formulation through and thus reducing the risk of drug abuse.

[0316] As used herein, the term "steady state" refers to a molecular concentration, e.g., a concentration of a molecule ... Describes the stable or steady-state level of a molecule concentration, such as the concentration of any compound present in a sample.

[0317] As used herein, the term "composition" is equivalent to the term "formulation."

[0318] As used herein, the term "administration event" refers to a short, e.g., less than 10 minutes, It describes administering a given dose to a subject in the form of one or more tablets within a time frame.

[0319] As used herein, the term "release period" refers to the period during which any compound described herein The time frame for the release of the compound from the matrix to achieve plasma concentrations of the compounds described herein is described. The start of the release period is defined from the time of oral administration to the subject, which is the time of gastric penetration. The initial dissolution rate is considered to be approximately equivalent to the initial dissolution rate due to gastric enzymes and acid. The end time is defined as the point at which the entire loaded drug is released. The period is more than approximately 4 hours, more than 8 hours, more than 12 hours, more than 16 hours, more than 20 hours, or approximately 24 hours. More than 28 hours, more than 32 hours, more than 36 hours, or more than 48 hours, or about 4 Less than 8 hours, less than 36 hours, 4 hours or less, 3 hours or less, 2 hours or less, or 1 hour or less It is possible.

[0320] As used herein, the term "treat" or "treatment" refers to the treatment of a mammal, e.g., means to treat or cure a disease or medical condition in a patient, especially a human, is a disease-causing agent, e.g., causing the elimination or regression of a disease or medical condition in a patient. or improving a medical condition, e.g., alleviating a disease or medical condition in a patient. To inhibit by slowing or halting the onset of a medical condition, or to improve the patient's In one embodiment, prophylactic treatment includes alleviating the symptoms of a disease or medical condition. , may prevent the occurrence of a disease or medical condition in a subject.

[0321] "Patient" refers to human and non-human subjects, particularly mammalian subjects.

[0322] As used herein, unless otherwise specified, the terms "prevent" and "not preventing" are used interchangeably. "Prevent" and "prevent" refer to the prevention of the onset of a disease, disorder, or condition, or one or more symptoms thereof. The term refers to the prevention of the onset, recurrence, or spread of a particular disease, disorder, or condition. Subjects with a family history of a disease, disorder, or condition may be particularly In certain embodiments, patients are candidates for prophylactic regimens. Elephants are also potential candidates for prevention. In this regard, the term "prevention" is used interchangeably with the term "prophylactic treatment." may be used interchangeably with.

[0323] As used herein, and unless otherwise specified, the terms "manage," "manage" and "manage" are used interchangeably. "Managing" and "managing" refer to the management of a disease, disorder, or condition, or one or more of these symptoms. It refers to preventing or slowing the progression, spread, or worsening of a condition. The beneficial effects obtained from the therapeutic agent(s) may not result in a cure of the disease, disorder, or condition. In this context, the term "managing" means preventing or reducing the recurrence of a disease, disorder, or condition. It involves treating a subject with a specific disease, disorder, or condition in order to minimize or eliminate the Includes.

[0324] A "pharmaceutically effective amount" and a "therapeutically effective amount" refer to a dose or amount of a compound or compound that is effective for a particular disorder or disease, or one thereof. The compound is sufficient to treat the above symptoms and / or prevent the occurrence of a disease or disorder. Refers to the amount of mixture.

[0325] As used herein, and unless otherwise specified, a "prophylactically effective amount" of an active agent. " is an amount sufficient to prevent or prevent the recurrence of a disease, disorder, or condition. The term "prophylactically effective amount" refers to an amount that improves overall prophylaxis or is more effective than the prophylaxis of another prophylactic agent. The amount of the active ingredient may include an amount that enhances the therapeutic effect.

[0326] The term "neurologically toxic spike" is used herein to refer to sedation or hallucinations, dizziness, and psychotomimetic effects such as nausea and vomiting, as described herein. It is used to describe a spike in the concentration of any compound that has an immediate effect. Not only do they cause side effects, but they also affect treatment compliance. g / L (e.g., about 300, 400, 500, 600, or more ng / L) This may be more pronounced at blood concentration levels that are higher than normal.

[0327] As used herein, and unless otherwise specified, "neuropsychiatric disorders or A "psychiatric disorder" is a behavioral or psychological problem associated with a known neurological condition, typically , defined as a constellation of coexisting symptoms. Examples of neuropsychiatric disorders include but are not limited to: Although not widely used, schizophrenia, cognitive impairment in schizophrenia, attention deficit disorder, and attention deficit hyperactivity disorder Attention Deficit Hyperactivity Disorder, Bipolar Disorder and Manic Depression, Depression, or any combination thereof Examples include combinations of

[0328] As used herein, an "inflammatory condition" or "inflammatory disease" refers broadly to any condition, whether chronic or acute. Inflammatory conditions and diseases include, but are not limited to, rheumatoid arthritis, rheumatoid arthritis, and inflammatory conditions and diseases. diseases (e.g., rheumatoid arthritis, osteoarthritis, psoriatic arthritis), spondyloarthropathies (e.g., ankylosing spondylitis, reactive arthritis, Reiter's syndrome), crystal arthropathy (e.g., gout, pseudogout) , calcium pyrophosphate deposition disease), multiple sclerosis, Lyme disease, polymyalgia rheumatica, Synthetic tissue diseases (e.g., systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, Sjögren's syndrome), vasculitis (e.g., polyarteritis nodosa, Wegener's granulomatosis, inflammatory conditions, including those resulting from trauma or ischemia; sarcoidosis; Atherosclerosis, atherosclerosis, and vascular occlusive diseases (e.g., arteriovenous arteriosclerosis, ischemic heart disease, myocardial infarction, stroke, peripheral vascular disease), and vascular stroke Vascular disease including tentorial restenosis, uveitis, corneal disease, iritis, iridocyclitis, and erythematous cornea Eye diseases including cataracts are included.

[0329] As used herein, the term "and / or" refers to any or all of the associated listed items. This includes any and all combinations of one or more of the following: As used throughout the claims, unless the context clearly indicates otherwise, "a," The meaning of "an" and "the" includes plural reference as well as singular reference. The term "about" in this context means that the value varies above and below 5%. For example, for a value of about 100, means 95 to 105 (or any value between 95 and 105).

[0330] compound

[0331] As used herein, the compounds of formula (I) or their optically pure stereoisomers, and a commercially acceptable salt, solvate, or prodrug thereof, wherein X1 and X2 are is deuterium, and Y1 and Y2 are deuterium. [ka]

[0332] In some embodiments, R is [ka] is.

[0333] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0334] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0335] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0336] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0337] In some embodiments, when R4 is hydroxyl, R8 and R9 are both -C If not D3, then R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, Unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkyl nyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl .

[0338] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. Then, R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or The aryl is selected from unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl.

[0339] In some embodiments, when R4 is hydroxyl, R9 is unsubstituted or substituted alkyl. If not, R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, non- It is selected from substituted or substituted aryl, and unsubstituted or substituted heteroaryl.

[0340] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0341] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0342] As used herein, a compound according to formula (Ia), or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed, wherein X and X 2 is deuterium, and Y1 and Y2 are deuterium. [ka]

[0343] In some embodiments, R is [ka] is.

[0344] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0345] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0346] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0347] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0348] In some embodiments, when R4 is hydroxyl, R8 and R9 are both -C If not D3, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkyl aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or Substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted alkyl The aryl is selected from aryl, and unsubstituted or substituted heteroaryl.

[0349] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. then R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl ... substituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and and unsubstituted or substituted heteroaryl.

[0350] In some embodiments, when R4 is hydroxyl, R9 is unsubstituted or substituted alkyl. If R9 is not hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl and unsubstituted or substituted heteroaryl.

[0351] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0352] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0353] As used herein, a compound according to formula (Ib), or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed, wherein X and X 2 is deuterium, and Y1 and Y2 are deuterium. [ka]

[0354] In some embodiments, R is [ka] is.

[0355] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0356] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0357] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0358] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0359] In some embodiments, when R4 is hydroxyl, R8 and R9 are both -C If not D3, then R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, Unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkyl nyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl .

[0360] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. Then, R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or The aryl is selected from unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl.

[0361] In some embodiments, when R4 is hydroxyl, R9 is unsubstituted or substituted alkyl. If not, R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, non- It is selected from substituted or substituted aryl, and unsubstituted or substituted heteroaryl.

[0362] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0363] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0364] As used herein, the compounds of formula (Ic) or optically pure stereoisomers thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0365] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0366] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0367] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0368] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0369] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0370] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0371] As used herein, the compounds of formula (Id) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0372] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0373] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0374] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0375] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0376] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0377] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0378] As used herein, the compounds of formula (Ie) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0379] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0380] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0381] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0382] In some embodiments, if R8 and R9 are not both -CD3, then R9 is hydrogen. , unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkene aryl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted cycloalkyl; or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted aryl. substituted heteroaryl.

[0383] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0384] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0385] As used herein, the compounds of formula (If) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0386] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0387] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0388] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0389] In some embodiments, if R8 and R9 are not both -CD3, then R9 and R 10 are independently hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted substituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and and unsubstituted or substituted heteroaryl.

[0390] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0391] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0392] As used herein, the compounds of formula (Ig) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0393] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0394] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0395] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0396] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0397] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0398] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0399] As used herein, the compounds of formula (Ih) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0400] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0401] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0402] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0403] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0404] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0405] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0406] As used herein, the compounds of formula (Ii) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0407] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0408] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0409] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0410] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0411] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0412] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0413] As used herein, the compounds of formula (Ij) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0414] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0415] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0416] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0417] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0418] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0419] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0420] As used herein, the compounds of formula (Ik) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0421] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0422] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0423] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0424] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0425] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0426] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0427] As used herein, the compounds of formula (II) or optically pure stereoisomers thereof, and a physiologically acceptable salt, solvate, or prodrug thereof, wherein X1 and X2 is deuterium, and Y1 and Y2 are hydrogen. [ka]

[0428] In some embodiments, R is [ka] is.

[0429] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0430] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0431] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0432] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0433] In some embodiments, R and R 10 are independently hydrogen, unsubstituted or substituted alkyl unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted aryl alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl aryl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; can be.

[0434] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0435] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0436] As used herein, a compound according to formula (II-a) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed, and X1 and X1 and X2 are deuterium, Y1 and Y2 are hydrogen, and R is [ka] is.

[0437] [ka]

[0438] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0439] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0440] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0441] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0442] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0443] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0444] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0445] As used herein, the compounds according to formula (II-b) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed, and X1 and X1 and X2 are deuterium, Y1 and Y2 are hydrogen, and R is [ka] is.

[0446] [ka]

[0447] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0448] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0449] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0450] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R8 is a partially or fully deuterated alkyl. In embodiments, R8 is partially or fully deuterated methyl or ethyl.

[0451] In some embodiments, R and R 10 are independently hydrogen, unsubstituted or substituted alkyl unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted aryl alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl aryl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; can be.

[0452] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0453] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0454] As used herein, the compounds according to formula (II-c) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed, and X1 and X1 and X2 are deuterium, Y1 and Y2 are hydrogen, and R is [ka] is.

[0455] [ka]

[0456] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0457] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0458] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0459] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. In some embodiments, R 10 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl. In the embodiment, R 10 is a partially or fully deuterated methyl or ethyl.

[0460] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0461] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0462] As used herein, the compound according to formula (II-d) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0463] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0464] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0465] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0466] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0467] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0468] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0469] As used herein, the compound according to formula (II-e) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed.

[0470] [ka]

[0471] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0472] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0473] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0474] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0475] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0476] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0477] As used herein, the compound according to formula (II-f) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0478] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0479] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0480] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0481] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0482] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0483] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0484] As used herein, the compound according to formula (II-g) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0485] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0486] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0487] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0488] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0489] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0490] As used herein, the compound according to formula (II-h) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0491] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0492] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0493] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0494] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0495] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0496] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0497] As used herein, the compounds according to formula (II-i) or optically pure stereoisomers thereof are Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0498] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0499] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0500] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0501] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0502] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0503] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0504] As used herein, the compound according to formula (II-j) or an optically pure stereoisomer thereof, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0505] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0506] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0507] In some embodiments, R8 is a partially or fully deuterated alkyl. In the form, R8 is a partially or fully deuterated methyl or ethyl.

[0508] In some embodiments, R9 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted substituted allyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted substituted aryl, and unsubstituted or substituted heteroaryl.

[0509] In some embodiments, unsubstituted or substituted alkyl is unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0510] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0511] As used herein, the compounds of formula (III) or their optically pure stereoisomers, Pharmaceutically acceptable salts, solvates, or prodrugs are disclosed. [ka]

[0512] In some embodiments, X1 and X2 are deuterium.

[0513] In some embodiments, Y 1 and Y 2 are hydrogen or deuterium.

[0514] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or In some embodiments, the aryl group is selected from substituted aryl, and unsubstituted or substituted heteroaryl. wherein R2 is independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely substituted. It is selected from fully deuterated methyl or ethyl.

[0515] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0516] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0517] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0518] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. In some embodiments, R8 is a partially or fully deuterated methyl or ethyl. Or ethyl.

[0519] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0520] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0521] In some embodiments, when R4 is hydroxyl, R9 is hydrogen.

[0522] In some embodiments, when R4 is hydroxyl, R9 is deuterium.

[0523] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0524] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0525] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0526] In some embodiments, the compound of formula (III) has formula (III-a), as described below: Formula (III-b), Formula (III-c), Formula (III-d), Formula (III-e), Formula (II If), formula (III-g), formula (III-h), formula (III-i), formula (III-j) , formula (III-k), formula (III-l), formula (III-m), formula (III-n), formula (I II-o), Formula (III-p), Formula (III-q), Formula (III-r), Formula (III-s ), formula (III-t), formula (III-u), formula (III-v).

[0527] As used herein, the compound according to formula (III-a) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0528] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0529] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0530] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0531] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0532] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0533] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0534] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0535] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. .

[0536] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0537] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0538] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0539] As used herein, the compound according to formula (III-b) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0540] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0541] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0542] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0543] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0544] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R9 are not unsubstituted methyl.

[0545] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0546] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0547] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0548] As used herein, the compound according to formula (III-c) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0549] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0550] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0551] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0552] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0553] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0554] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0555] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0556] As used herein, the compounds according to formula (III-d) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0557] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0558] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0559] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0560] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0561] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R 9 are both -CD3.

[0562] In some embodiments, R9 is hydrogen.

[0563] In some embodiments, R9 is deuterium.

[0564] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0565] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0566] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0567] As used herein, the compounds according to formula (III-e) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0568] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0569] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0570] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0571] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0572] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0573] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0574] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0575] As used herein, the compounds of formula (III-f) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0576] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0577] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0578] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0579] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0580] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0581] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0582] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0583] As used herein, the compound according to formula (III-g) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0584] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0585] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0586] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0587] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0588] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0589] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0590] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0591] As used herein, the compounds of formula (III-h) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0592] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0593] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0594] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0595] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0596] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0597] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0598] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0599] As used herein, the compounds according to formula (III-i) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0600] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0601] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0602] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0603] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0604] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0605] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0606] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0607] As used herein, the compound according to formula (III-j) or an optically pure stereoisomer thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0608] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0609] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0610] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0611] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0612] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0613] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0614] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0615] As used herein, the compounds of formula (III-k) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0616] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or selected from substituted aryl, and unsubstituted or substituted heteroaryl;

[0617] In some embodiments, R4 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy.

[0618] In some embodiments, R5 is independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted. The alkyl group is selected from substituted alkoxy, and phosphoryloxy.

[0619] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0620] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0621] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0622] In some embodiments, R4 is hydroxyl and R2, R5, R6, and R7 are all hydrogen, R8 and R9 are not both -CD3, and R2, R4, R5 When R, R, and R are all hydrogen, R and R are both unsubstituted methyl. do not have.

[0623] In some embodiments, when R4 is hydroxyl, R9 is hydrogen or deuterium. .

[0624] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0625] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0626] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. In some embodiments, the alkoxy is methoxy or ethoxy.

[0627] As used herein, the compounds according to formula (III-1) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0628] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0629] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0630] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0631] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0632] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R9 are not unsubstituted methyl.

[0633] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0634] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0635] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0636] As used herein, the compounds of formula (III-m) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0637] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0638] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0639] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0640] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0641] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0642] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0643] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0644] As used herein, the compounds of formula (III-n) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0645] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0646] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0647] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0648] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0649] In some embodiments, when R2, R6, and R7 are all hydrogen, R8 and R 9 are both -CD3.

[0650] In some embodiments, R9 is hydrogen.

[0651] In some embodiments, R9 is deuterium.

[0652] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0653] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0654] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0655] As used herein, the compounds of formula (III-o) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0656] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0657] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0658] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0659] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0660] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0661] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0662] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0663] As used herein, the compounds of formula (III-p) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0664] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0665] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0666] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0667] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0668] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0669] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0670] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0671] As used herein, the compounds of formula (III-q) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0672] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0673] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0674] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0675] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0676] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0677] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0678] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0679] As used herein, the compounds of formula (III-r) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0680] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0681] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. ,

[0682] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0683] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0684] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0685] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0686] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0687] As used herein, the compounds of formula (III-s) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0688] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0689] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0690] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0691] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0692] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0693] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0694] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0695] As used herein, the compounds of formula (III-t) or optically pure stereoisomers thereof are , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0696] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0697] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0698] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0699] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0700] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0701] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0702] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0703] As used herein, the compounds of formula (III-u) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0704] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0705] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0706] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0707] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0708] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0709] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0710] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0711] As used herein, the compounds according to formula (III-v) or optically pure stereoisomers thereof , pharmaceutically acceptable salts, solvates, or prodrugs thereof are disclosed. [ka]

[0712] In some embodiments, R2 is independently hydrogen, deuterium, unsubstituted or substituted alkyl, non Substituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, non substituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or It is selected from substituted aryl, and unsubstituted or substituted heteroaryl.

[0713] In some embodiments, R6 and R7 are selected from hydrogen, deuterium, and halogen. do.

[0714] In some embodiments, R8 is an unsubstituted or partially or fully deuterated methyl group. It is methyl or ethyl.

[0715] In some embodiments, R9 is hydrogen, deuterium, or unsubstituted or partially or fully substituted. It is a fully deuterated methyl or ethyl.

[0716] In some embodiments, R2 is independently selected from hydrogen, deuterium, halogen, and unsubstituted or It is selected from partially or fully deuterated methyl or ethyl.

[0717] In some embodiments, R8 and R9 are both unsubstituted or partially or fully substituted. It is not hydrogenated ethyl.

[0718] In some embodiments, "substituted" refers to partial or complete substitution with deuterium. For example, substituted alkyl is partially or fully deuterated alkyl. .

[0719] In some embodiments, the compound is selected from the following: [ka] [ka] [ka] [ka]

[0720] In some embodiments, the compound has the structure: [ka]

[0721] In some embodiments, the compounds described herein are deuterium or deuterium substituted. R2, R4, R5, R6, R7, R9, and R 10 At least one of Has.

[0722] In some embodiments, the compounds described herein are selected from the group consisting of R2, R4, R5, R6, and R At least one of the seven is deuterium or is substituted with deuterium.

[0723] In some embodiments, R2 in the compounds described herein is deuterium or is replaced by .

[0724] In some embodiments, R4 in the compounds described herein is deuterium or is replaced by .

[0725] In some embodiments, R5 in the compounds described herein is deuterium or is replaced by .

[0726] In some embodiments, R6 in the compounds described herein is deuterium or is replaced by .

[0727] In some embodiments, R7 in the compounds described herein is deuterium or is replaced by .

[0728] In some embodiments, R9 in the compounds described herein is deuterium or is replaced by .

[0729] In some embodiments, R of the compounds described herein 10 is deuterium or heavy water It is replaced by an element.

[0730] In some embodiments, R6 and / or R7 of the compounds described herein are halogen. be.

[0731] In some embodiments, R4 and / or R5 of the compounds described herein are deuterium. or substituted with deuterium.

[0732] In some embodiments, the compound is an agonist of the serotonin 5-HT2 receptor.

[0733] In some embodiments, the compound is serotonin 5-HT 2A may be an agonist of the receptor do.

[0734] Without being bound to any particular theory, selective The novel compounds described herein with suitable deuteration may provide improved exposure (i.e., Significant delay in enzymatic degradation due to prevention of acute high drug concentration (spike) observed after administration and increased blood / brain ratio, which is thought to result in improved oral bioavailability Some compounds described herein can be prepared by selective deuteration of the phenyl ring to give similar Bring profit.

[0735] Pharmaceutical compositions comprising the compounds disclosed herein and a pharmaceutically acceptable vehicle are also disclosed herein. Disclosed in the specification.

[0736] A "pharmaceutically acceptable vehicle" is a vehicle approved by a federal or state government regulatory agency. or as otherwise specified in the United States Pharmacopoeia or other commonly used The vehicle may be any vehicle described in a recognized pharmacopoeia. a diluent, adjuvant, excipient with which the compound is formulated for administration to a mammal, or Such pharmaceutical vehicles may be derived from petroleum, animal, vegetable, or plant oils, such as peanut oil, soybean oil, or other vegetable oils. It may be a liquid such as water and oil, including those of synthetic origin such as oil, mineral oil, sesame oil, etc. Pharmaceutical vehicles include saline, gum acacia, gelatin, starch paste, talc, It may be keratin, colloidal silica, urea, etc. In addition, auxiliary agents, stabilizers, thickeners, moisturizers, etc. Lubricating and coloring agents can be used.

[0737] When administered to a mammal, the compounds and compositions of the present disclosure, as well as pharmaceutically acceptable The vehicle, excipient, or diluent may be sterile. When administered intravenously, water, saline, and aqueous dextrose and glycerol An aqueous medium such as roll solution is used as the vehicle.

[0738] The pharmaceutical composition may be in the form of a capsule, tablet, pill, pellet, throat lozenge, powder, granule, syrup, Elixirs, solutions, suspensions, emulsions, suppositories, or sustained-release formulations thereof, or oral It may take the form of any other suitable form for administration to a mammal. The composition may be administered in a routine manner as a pharmaceutical composition adapted for oral or intravenous administration to humans. Examples of suitable pharmaceutical vehicles and methods of their formulation are: Law, Remington: The Science and Practice o f Pharmacy, Alfonso R. Gennaro ed., Mack Publishing Co. Easton, Pa., 19th ed., 1995 ,Chapters 86, 87, 88, 91, and 92, which are described in The choice of excipient will depend on the particular compound and on the composition. The amount of time that the drug is administered will be determined in part by the particular method used to administer the drug. Accordingly, there is a wide variety of suitable formulations of the subject pharmaceutical compositions.

[0739] Administration of the subject compounds can be systemic or local. In some embodiments, the subject compounds are administered to a mammal. Administration of results in systemic release (e.g., into the bloodstream) of the compounds of the present disclosure. , enteral routes such as buccal, sublingual, and rectal; topical administration such as transdermal and intradermal; Administration by inhalation via a bladder or inhaler, and parenteral administration may be included.

[0740] In some embodiments, the composition comprises at least 50% of the total amount of isotopologues of the formula present. In some embodiments, the compounds disclosed herein contain deuterium. Any position in the compound must have a minimum deuterium incorporation of at least 45% deuterium. In some embodiments, the composition is substantially free of other isotopologues of the compound.

[0741] In some embodiments, the pharmaceutical composition comprises: (i) a water-insoluble, neutrally charged non-ionic matrix; and (ii) comprising a polymer bearing one or more negatively charged groups.

[0742] In some embodiments, the non-ionic matrix is ​​a cellulosic polymer such as HPMC. Alone or with starch, wax, neutral rubber, polymethacrylate, PVA, PVA / P H reinforced by blending with components such as VP blends or mixtures thereof In some embodiments, the cellulosic polymer is selected from the group consisting of cellulose-based polymers such as PMC. The polymer is hydroxypropyl methylcellulose (HPMC).

[0743] In some embodiments, the polymer carrying one or more negatively charged groups is polyacrylic acid, poly(ethylene glycol). Polylactic acid, polyglycolic acid, polymethacrylate carboxylate, cation exchange resin, Clay, zeolite, hyaluronic acid, anionic gums, their salts, or mixtures thereof is.

[0744] In some embodiments, the anionic rubber is a natural or semi-synthetic material. In an embodiment, the natural material is alginic acid, pectin, xanthan gum, carrageenan Locust bean gum, gum arabic, gum karaya, guar gum, gum tragacanth or a mixture thereof. In some embodiments, the semi-synthetic material is carboxymethyl chitin, cellulose gum, or a mixture thereof.

[0745] In some embodiments, a modified release oral formulation is provided. The agents may be constructed using either deuterated or non-deuterated tryptamine. This allows for the administration of low-dose maintenance drugs that utilize tryptamine's ability to bind to anionic polymers. It is for chronic treatment.

[0746] The pharmaceutical compositions may be prepared and administered in a wide variety of dosage forms. Orally, rectally, by inhalation, or by injection (e.g., intravenously, intramuscularly, intradermally, subcutaneously, It may be administered intravenously (intradenally, intravenously, or intraperitoneally).

[0747] To prepare pharmaceutical compositions from the compounds described herein, a pharmaceutically acceptable carrier may be used. The bodies can be either solid or liquid. Solid form preparations include powders, tablets, pills, etc. Solid carriers include diluents, flavorings, and dispersible granules. One or more substances that may also function as flavoring agents, binders, preservatives, tablet disintegrating agents, or encapsulating materials may be.

[0748] In powders, the carrier is a finely divided solid in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary binding properties in suitable proportions. The mixture may be compressed into a desired shape and size.

[0749] The powders and tablets may contain from about 5% to about 70% of the active compound. Suitable carriers are carbonated Magnesium, magnesium stearate, talc, sugars, lactose, pectin, dextrin , starch, gelatin, tragacanth, methylcellulose, carboxymethylcellulose The term "preparation" does not include other carriers such as sodium hydroxide, a low melting wax, cocoa butter, etc. A carrier that provides a capsule in which the active ingredient, with or without, is surrounded by the carrier. It is intended to include formulations of active compounds having an encapsulating material as an active ingredient, and therefore Also included are cachets and lozenges. Tablets, powders, capsules Cells, pills, cachets, and lozenges are used as solid dosage forms suitable for oral administration. It is possible.

[0750] To prepare suppositories, low melting water such as a mixture of fatty acid glycerides or cocoa butter is used. The solvent is first dissolved and the active ingredient is dispersed uniformly therein by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby and solidify.

[0751] Liquid preparations include, for example, solutions such as water or water / propylene glycol solutions; For parenteral injection, liquid preparations include aqueous suspensions and emulsions. It can also be formulated in solution in polyethylene glycol solution.

[0752] Aqueous solutions suitable for oral use may be prepared by dissolving the active ingredient in water and adding suitable colorants, flavors, or other additives, if desired. It can be prepared by adding flavoring agents, stabilizers, and thickeners. The aqueous suspension contains natural or synthetic rubbers, resins, methylcellulose, carboxymethylcellulose, finely divided suspensions using viscous materials such as sodium cellulose and other well-known suspending agents. The dispersion may be prepared by dispersing the active ingredient in water.

[0753] Also, solid forms that are intended to be converted, shortly before use, into liquid form preparations for oral administration may be used. Liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active ingredient, colorants, flavors, stabilizers, buffers, artificial colors, and artificial flavors. and natural sweeteners, dispersants, thickeners, solubilizers, etc.

[0754] The pharmaceutical preparations may be in unit dosage form. In such form, the preparation contains the active ingredient The unit dosage form may be a packaged preparation, e.g., a portioned preparation, containing an appropriate amount of the active ingredient. Preparing discrete doses such as packaged tablets, capsules, and powders in vials or ampoules The unit dosage form may also be a capsule, tablet, cachet, or The lozenges may be the lozenges themselves, or any suitable number of these in a packaged form. That's fine.

[0755] The quantity of active ingredient in a unit dose preparation may range from about 0 to 100 mg, depending on the particular application and the potency of the active ingredient. 0.001 mg to about 10 mg (e.g., about 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 mg or more, or any range from about 0.001 to about 10.0 mg (e.g. , about 0.0001 to about 0.1, about 0.1 to 1.0, about 0.0005 to 0.5, or about 0 The amount of hydroxybenzoates may be varied or adjusted, for example, from about 0.01 to about 2.0 mg. The composition may be, if desired, Other compatible therapeutic agents may also be included.

[0756] Some compounds have limited solubility in water and therefore require surfactants in the composition. or other suitable co-solvents may be required. Such co-solvents include polysorbate 20, 60, , and 80, Pluronic F-68, F-84, and P-103, cyclodextrin Such co-solvents typically include: It is used at a level of about 0.01% to about 2% by weight. It has a viscosity greater than that of a simple aqueous solution. The stability reduces variability in dispensing the formulation and improves the physical properties of the components of the formulation suspension or emulsion. It may be desirable to reduce environmental segregation and / or otherwise improve the formulation. Such viscosity building agents include, for example, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, Carboxymethylcellulose, hydroxypropylcellulose, chondroitin sulfate, and salts thereof, hyaluronic acid and salts thereof, and combinations of the foregoing. Typically, it is used at a level of about 0.01% to about 2% by weight.

[0757] The pharmaceutical composition may include additional components to provide sustained release and / or sustained comfort. Such components may include high molecular weight, anionic mucus-mimetic polymers, gels, and the like. These components include: cellulose polysaccharides, and a finely divided drug carrier substrate. National Patent Nos. 4,911,920, 5,403,841, 5,212,162, and and 4,861,760, the entire contents of which are incorporated herein by reference. and is hereby incorporated herein in its entirety for all purposes.

[0758] The pharmaceutical composition may be intended for intravenous use. The pharmaceutically acceptable excipients may be pH Buffers may be included to adjust the concentration to a desired range for intravenous use. Phosphate, boric acid Many buffers are known, including salts and salts of inorganic acids such as sulfates.

[0759] A pharmaceutical composition may comprise a composition, wherein the active ingredient is present in a therapeutically effective amount, i.e., It is contained in an amount effective to achieve the intended purpose. The actual amount will depend, inter alia, on the condition being treated.

[0760] The dose and frequency (single or multiple doses) of the compound administered will depend on the route of administration, the recipe, the size, age, sex, health, weight, body mass index, and diet of the patient, and the symptoms of the disease being treated. the nature and severity of the condition, the presence of other illnesses or other health problems, the type of concomitant medication, and and complications from any disease or treatment regimen. Other therapeutic regimens or agents may be used in conjunction with the methods and compounds disclosed herein. It is possible.

[0761] Therapeutically effective amounts for use in humans may be determined from animal models. Doses for the compound are formulated to achieve concentrations found to be effective in animals. The dosage in humans may be determined based on the response to treatment of constipation or dry eye, as described above. can be monitored and adjusted by adjusting the dose upward or downward.

[0762] Dosages may vary depending on the requirements of the subject and the compound used. In the context of a pharmaceutical composition, the dose administered to a subject is such that a beneficial therapeutic response is achieved in the subject over time. The size of the dose should also be considered to determine the presence of adverse side effects, Generally, treatment will be initiated at a dose lower than the optimum dose of the compound. The dose is then increased to the optimum effect under the circumstances. Increase in small increments until it is reached.

[0763] Dosage amounts and intervals are determined to provide levels of the administered compound that are effective for the particular clinical indication being treated. This allows for individualized treatment to be tailored to the severity of an individual's disease state. A suitable treatment regimen will be provided.

[0764] Utilizing the teachings provided herein, it is possible to achieve a therapeutic effect in certain patients without causing substantial toxicity. effective prophylactic or therapeutic agent that is completely effective in treating the clinical symptoms indicated by the A treatment regimen can be designed, which will depend on the potency, relative bioavailability, and other factors of the compounds. The patient's weight, the presence and severity of adverse side effects, the preferred mode of administration, and the type of drug selected will all be taken into consideration. Careful selection of active compounds is ensured by considering factors such as the toxicity profile of the selected drug. This should include choosing

[0765] Also disclosed are methods for treating a disease, comprising administering to a subject a therapeutically effective amount of a compound disclosed herein. Alternatively, methods of treating a subject having a disorder are disclosed.

[0766] Also disclosed are methods for treating a disease, comprising administering to a subject a therapeutically effective amount of a compound disclosed herein. Alternatively, methods of treating a subject having a disorder are disclosed.

[0767] Also disclosed are methods for treating cerebrovascular disease, including administering to a subject a therapeutically effective amount of a compound disclosed herein. Methods of treating a subject having a disease or disorder associated with the tonic 5-HT2 receptor are disclosed. In some embodiments, the compound has the structure: [ka]

[0768] In some embodiments, administration of the disclosed methods is by oral, sublingual, buccal, parenteral, topical, nasal, or the like. Administration by cavity, inhalation, or injectable routes.

[0769] In some embodiments, the disease or disorder is major depressive disorder (MDD), suicidal ideation or Major depressive disorder with suicidal behavior (MDD), suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSI) SSID), Treatment-Resistant Depression (TRD), Post-Traumatic Stress Disorder (PTSD), Bipolar Bipolar and related disorders, including bipolar I disorder, bipolar II disorder, and cyclothymic disorder; obsessive-compulsive disorder (OCD); CD), generalized anxiety disorder (GAD), social anxiety disorder, alcohol use disorder, opioids substance use disorder, including use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headaches and migraines, Attention-deficit hyperactivity disorder (ADHD), pain and neuropathic pain, aphantasia, childhood onset Fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, leukemia from the group consisting of central nervous system (CNS) disorders, including rheumatoid arthritis, obesity, or a combination thereof. In some embodiments, the disease or disorder is an alcohol use disorder.

[0770] In some embodiments, the disease or disorder comprises a condition of the autonomic nervous system (ANS).

[0771] In some embodiments, the disease or disorder includes asthma and chronic obstructive pulmonary disorder (COPD). Including lung disorders.

[0772] In some embodiments, the disease or disorder is a cardiovascular disorder, including atherosclerosis. include.

[0773] Also, treating subjects with alcohol use disorders associated with the serotonin 5-HT2 receptor. 1. A method for treating a cancer, comprising administering to a subject a therapeutically effective amount of a compound having the structure: A method is disclosed. [ka]

[0774] formulation Also disclosed herein are compounds that have reduced neurological adverse effects compared to existing oral formulations, For example, pills (e.g., tablets, capsules, caplets, lozenges, cough drops, etc.) , gel caps, caps, pellets, boluses, pastilles, orally disintegrating tablets, sublingual tablets and Pharmaceutical compositions formulated for oral administration, such as oral tablets, DMT, 5-MeO-DMT , a tryptamine derivative such as psilocybin, psilocin, or a compound described herein or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions, such as formulated pharmaceutical compositions, are disclosed. Any of the compounds listed above (e.g., DMT, 5-MeO-DMT, psilocybin, and psilocin) a liptamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof Oral administration of benzodiazepine (a possible salt) without analgesic or psychotomimetic toxicity spikes in plasma concentrations Ensuring a steady release of therapeutically effective concentrations of the tryptamine derivatives described herein from the pharmaceutical composition. Such spikes in plasma concentrations can cause hallucinations, dizziness, and side effects. May have serious psychotomimetic side effects, including but not limited to: This has been documented in the literature, which has immediate impacts on treatment compliance as well. In this regard, the present disclosure provides, for example, a method for reducing analgesic and psychotomimetic side effects. Tryptophan, such as DMT, 5-MeO-DMT, psilocybin, and psilocin, with reduction or any of the compounds described herein, or pharmaceutically acceptable salts thereof. for oral administration, containing the optimal matrix discovered for long-term steady release of soluble salts. To provide a new and original formulation.

[0775] In some embodiments, the pharmaceutical composition (e.g., a monolayer tablet composition formulated for oral administration) The tablet composition contains the compounds described herein (DMT, 5-MeO-DMT, silico). tryptamine derivatives such as psilocin, and psilocin, or the compounds described herein In some embodiments, the compound includes either benzophenone-3, benzophenone-4, benzodibenzofuranone ... The compound has the following structure: [ka]

[0776] In some embodiments of the present disclosure, the tablet composition is adapted for sustained release, e.g., maximum sustained release. It is a modified release tablet.

[0777] In some embodiments of the present disclosure, the tablet composition is adapted to be tamper-resistant. In the form of a tablet composition, for example, about 2,000 to about 7,000 hydroxybenzoates in combination with HPMC. In some embodiments, the tablet contains polyethylene oxide (PEO) with a MW of 1000 MPa. The composition may further comprise polyethylene glycol (PEG), such as, for example, PEG8K. In some embodiments, the tablet composition comprises one or more negatively charged polymers, such as, for example, polyacrylic acid. In certain embodiments, the tablet composition may further comprise a polymer carrying a loading group. The article may be further subjected to heating / annealing, such as extrusion conditions.

[0778] In some embodiments of the present disclosure, the pharmaceutical composition comprises: (i) a water-insoluble, neutrally charged, non-ionic matrix; (ii) a polymer bearing one or more negatively charged groups, and (iii) DMT, 5 -Tryptamine derivatives such as MeO-DMT, psilocybin, and psilocin, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof, include.

[0779] In some embodiments of the present disclosure, the polymer carrying one or more negatively charged groups is a polyacrylic Polylactic acid, polyglycolic acid, polymethacrylate carboxylate, cation exchange Resins, clays, zeolites, hyaluronic acid, anionic gums, their salts, or In some embodiments, the anionic rubber is a mixture of natural, semi-synthetic, or In some embodiments, the natural material is alginic acid, PEG-100, or a combination thereof. Cutin, xanthan gum, carrageenan, locust bean gum, gum arabic, karaya gum, guar gum, gum tragacanth, or a combination thereof. In this study, semi-synthetic materials were carboxymethyl-chitin, cellulose gum, or combinations thereof. It's a combination.

[0780] Furthermore, without intending to be bound by theory, in some embodiments, e.g. For example, one or more loads bearing moieties of acidic nature, such as the acidic polymers described herein. The role of the polymer carrying the charge groups is surprisingly similar to that of the matrix containing DMT, 5-Me. Tryptamine derivatives such as O-DMT, psilocybin, and psilocin, or resulting in significant retention of any of the compounds described, or pharmaceutically acceptable salts thereof. In some embodiments, this negative charge is based on, for example, the release of a proton due to the pKa. , and generated in situ under specific pH conditions or via electrostatic interactions / negative charge generation Additionally, acidic polymers can be used to inhibit the release of corresponding weak acids that become the relevant protonated acids in the stomach. It is also noted that, without intending to be bound by theory, this may be a salt. Neutralizes the charge and prevents triphosphatidylcholine (TPP) synthesis, such as DMT, 5-MeO-DMT, psilocybin, and psilocin. a methamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof In addition, the release matrix may contain a filler. Preparation of suitable solid dosage forms, including additives such as disintegrants, flow improvers, lubricants, colorants, and taste masking agents. It may be further supplemented with other inactive pharmaceutical ingredients to aid in manufacturing.

[0781] In some embodiments of the present disclosure, the tablet composition is adapted to be tamper-resistant. In the form of a tablet composition, for example, a polysaccharide having a MW of about 2,000 to about 7,000 kDa is used. ethylene oxide (PEO). In certain embodiments, the tablet composition comprising PEO is For example, further exposure to heating / annealing such as extrusion.

[0782] In some embodiments of the present disclosure, the non-ionic matrix is ​​a cellulosic matrix such as HPMC. Polymer alone or in combination with starch, wax, neutral rubber, polymethacrylate, PVA, P Reinforced by mixing with components such as VA / PVP blends or mixtures thereof The polymer is selected from cellulosic polymers such as HPMC.

[0783] In some embodiments of the present disclosure, the cellulosic polymer is hydroxypropyl methylcellulose. In some embodiments, the tablet composition comprises about 20-60% by weight of HPMC. hydroxypropyl methylcellulose, about 10 to 30% by weight of starch, or This includes any combination of:

[0784] In some embodiments, the tablet composition contains any of the compounds described herein for the treatment of pain. In some embodiments, the pain being treated is cancer pain, e.g., intractable pain. In some embodiments, the pain being treated is post-operative pain. In some embodiments, the pain being treated is orthopedic pain. In some embodiments, the pain being treated is neuropathic pain. In some embodiments, the pain being treated is toothache. The pain is chronic in opioid-tolerant patients.

[0785] In some embodiments, the tablet composition comprises any of the compounds described herein for the treatment of depression. The present invention includes a therapeutically effective amount of the compound.

[0786] In some embodiments, the tablet composition comprises any of the compounds described herein for the treatment of brain injury. The present invention includes a therapeutically effective amount of the compound.

[0787] In some embodiments, the tablet composition comprises any of the compounds described herein for the treatment of stroke. The present invention includes a therapeutically effective amount of the compound.

[0788] In some embodiments, the tablet composition is a composition for use in, for example, migraine with aura. It includes a therapeutically effective amount of any compound described herein.

[0789] In some embodiments, the tablet composition comprises a compound as described herein for use in refractory asthma. The present invention includes a therapeutically effective amount of any compound of the present invention.

[0790] In some embodiments, the tablet composition is a composition as described herein for use in treating alcoholism. The present invention includes a therapeutically effective amount of any compound described in

[0791] In some embodiments, the tablet composition is for the treatment of post-traumatic stress disorder (PTSD). The present invention includes a therapeutically effective amount of any compound described herein for the treatment of a patient with atopic dermatitis.

[0792] In some embodiments, the tablet composition is for treating depression (e.g., treatment-resistant depression (TRD) or or bipolar disorder, comprising a therapeutically effective amount of any compound described herein for use in the treatment of .

[0793] In some embodiments, the tablet composition is for use in the treatment of major depressive disorder (MDD). A therapeutically effective amount of any compound described herein is included.

[0794] In some embodiments, the tablet composition is for use in treating anxiety (e.g., generalized anxiety disorder). The present invention includes a therapeutically effective amount of any compound described herein for the treatment of a patient suffering from atopic dermatitis.

[0795] In some embodiments, the tablet composition comprises a compound as described herein for use in treating schizophrenia. The present invention includes a therapeutically effective amount of any compound of the present invention.

[0796] In some embodiments, the tablet composition comprises a compound as described herein for use in treating bipolar disorder. The present invention includes a therapeutically effective amount of any compound of the present invention.

[0797] In some embodiments, the tablet composition is for use in treating suicidal tendencies or suicidal ideation. It includes a therapeutically effective amount of any compound described herein.

[0798] In some embodiments, the tablet composition comprises any of the compounds described herein for use in treating autism. The term "therapeutically effective amount" includes a therapeutically effective amount of any compound.

[0799] In some embodiments, the tablet composition is a composition as described herein for use in treating diabetic neuropathy. The present invention includes a therapeutically effective amount of any compound described in

[0800] In some embodiments, the tablet composition comprises a compound according to any of the compounds described herein for use in treating neuropathic pain. The present invention includes a therapeutically effective amount of any of the compounds described above.

[0801] In some embodiments, the tablet composition is used to treat acute pain (e.g., acute trauma pain). The present invention also includes a therapeutically effective amount of any compound described herein for:

[0802] In some embodiments, the tablet composition comprises a composition comprising a compound as described herein for use in treating chronic pain. A therapeutically effective amount of any compound is included.

[0803] In some embodiments, the tablet composition is for use in treating levodopa-induced dyskinesia. A therapeutically effective amount of any compound described herein.

[0804] In some embodiments, the tablet composition is used to treat and regulate pseudobulbar effect or ocular function. The present invention also includes a therapeutically effective amount of any compound described herein for:

[0805] In some embodiments, the tablet composition is a compound that inhibits Alzheimer's disease or Alzheimer's disease (e.g., For the treatment of conditions associated with Alzheimer's disease (e.g., dementia or agitation due to Alzheimer's disease) The present invention includes a therapeutically effective amount of any compound described herein for use.

[0806] In some embodiments, the tablet composition comprises any of the compounds described herein for use in treating tinnitus. The term "therapeutically effective amount" includes a therapeutically effective amount of any compound.

[0807] In some embodiments, the tablet composition is used to treat a disease or condition associated with the serotonin 5-HT2 receptor. includes a therapeutically effective amount of any compound described herein for use in treating a disorder.

[0808] In some embodiments, the disease or disorder is major depressive disorder (MDD), suicidal ideation or Major depressive disorder with suicidal behavior (MDD), suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSI) SSID), Treatment-Resistant Depression (TRD), Post-Traumatic Stress Disorder (PTSD), Bipolar Bipolar and related disorders, including bipolar I disorder, bipolar II disorder, and cyclothymic disorder; obsessive-compulsive disorder (OCD); CD), generalized anxiety disorder (GAD), social anxiety disorder, alcohol use disorder, opioids substance use disorder, including use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headaches and migraines, Attention-deficit hyperactivity disorder (ADHD), pain and neuropathic pain, aphantasia, childhood onset Fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, leukemia from the group consisting of central nervous system (CNS) disorders, including rheumatoid arthritis, obesity, or a combination thereof. In some embodiments, the disease or disorder is an alcohol use disorder.

[0809] In some embodiments, the disease or disorder comprises a condition of the autonomic nervous system (ANS).

[0810] In some embodiments, the disease or disorder includes asthma and chronic obstructive pulmonary disorder (COPD). Including lung disorders.

[0811] In some embodiments, the disease or disorder is a cardiovascular disorder, including atherosclerosis. include.

[0812] Depression, anxiety, or stress can contribute to Alzheimer's disease, autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, and psoriasis), cancer, coronary heart disease, diabetes, seizures Cancer, HIV / AIDS, hypothyroidism, multiple sclerosis, Parkinson's disease, and stroke It may be common in patients with chronic and / or life-threatening illnesses such as diabetes. Symptoms of depression, anxiety, or stress may occur after the diagnosis of an illness or disease. Patients who have depression, anxiety, or stress at the same time as a chronic illness or disease may experience both. may have more severe symptoms of the disease and depression, anxiety, or stress may be present The effects of the compounds described herein may continue even as the patient's physical health improves. The preparation is used to treat depression associated with a chronic or life-threatening illness or disease. It can be used.

[0813] In some embodiments, the tablet composition is administered over a period of 12 to 24 hours, e.g., 24 hours. The compounds described herein are released from the matrix at a rate of 0.05 to 2 mg / kg / h. Contains any quantity of something.

[0814] In some embodiments of the present disclosure, the composition comprises DMT, 5-MeO-DMT, psilocybin, a tryptamine derivative such as psilocin, or any of the compounds described herein, or or its pharmaceutically acceptable salts, in plasma at a combined concentration of about 10 to 500 ng / ml (e.g., For example, approximately 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 35 0, 400, 450, 500 ng / ml or more (or, for example, about 100 ~ about 300ng / ml, about 250 to about 450ng / ml, or about 50 to about 400ng / The release period is achieved in the range of about 10 to about 500 ng / ml, for example, in any range of about 10 to about 500 ng / ml. This concentration is maintained. In some embodiments, the composition is in the range of about 10 to 300 ng / ml. Triple-chain amino acids such as DMT, 5-MeO-DMT, psilocybin, and psilocin in the plasma of a methamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof In some embodiments, the composition achieves a complex concentration of the salt and maintains this concentration for the duration of the release period. The substance is in the range of about 10-100 ng / ml, or about 50-100 ng / ml in plasma. Tryptamine derivatives such as psilocybin, DMT, 5-MeO-DMT, psilocybin, and psilocin or a combined concentration of any of the compounds described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the composition achieves a concentration of about 10 Plasma concentrations of DMT, 5-MeO-DMT, psilocybin, and tryptamine derivatives such as psilocin, or any of the compounds described herein; achieves a complex concentration of the pharmaceutically acceptable salt and maintains this concentration over the release period.

[0815] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is 4 hours or less, 3 hours or less, It is either 2 hours or less, or 1 hour or less.

[0816] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof has a release period of greater than 4 hours.

[0817] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is greater than about 8 hours.

[0818] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is greater than about 12 hours.

[0819] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof has a release period of greater than about 16 hours.

[0820] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof has a release period of greater than about 20 hours.

[0821] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is about 24 hours or longer.

[0822] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is about 28 hours or longer.

[0823] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is about 32 hours or longer.

[0824] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is about 36 hours or longer.

[0825] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, the release period is less than about 48 hours.

[0826] In some embodiments of the present disclosure, the DMT, 5-MeO-DMT, Tryptamine derivatives such as psilocybin and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof, has a release period of less than about 36 hours.

[0827] In some embodiments of the present disclosure, the tablet compositions of the present disclosure are administered twice daily (BID), three times daily (TID), or both. (TID) or four times a day (QID) filing.

[0828] In some embodiments of the present disclosure, the tablet compositions of the present disclosure are useful for once-daily (QD) use. It is used.

[0829] In some embodiments of the present disclosure, the tablet compositions of the present disclosure are utilized for overnight (QHS) use. will be done.

[0830] In some embodiments of the present disclosure, the tablet compositions of the present disclosure are for as-needed (PRN) use and It is used as such.

[0831] In some embodiments of the present disclosure, the oral pharmaceutical composition is fortified. With the given efficiency, it achieves the same effect as a comparative oral tablet not described by this disclosure. Therefore, the formulation contains smaller amounts of DMT, 5-MeO-DMT, psilocybin, and tryptamine derivatives such as psilocin can be utilized.

[0832] In some embodiments of the present disclosure, the oral administration event that provides the appropriate single unit dose is It may contain one single tablet or multiple tablets.

[0833] Additionally, in some embodiments, the tablet is formulated to protect the tablet from the acidic environment in the stomach and maintain extended release. In the present invention, various types of enteric coatings may be used.

[0834] In some embodiments of the present disclosure, the monolayer tablet or caplet provides protection for the inactive pharmaceutical ingredients. The matrix may be coated with a layer to ensure, for example, a steady release of the drug from the matrix and an early release point. To avoid a concentration burst at 2000 kJ / kg, a modified release formulation is formed.

[0835] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or The formulation of the pharmaceutically acceptable salt of is provided as a modified release formulation, which provides such oral release From the modulating formulation, any compound described herein (DMT, 5-MeO-DMT, psilocybin tryptamine derivatives such as psilocin, or any of the compounds described herein analgesia or psychotropic effects in plasma concentrations of DMT, 5-MeO-DMT, psilocybin, and psilocybin without toxic spikes in expression a tryptamine derivative such as tryptamine, or any of the compounds described herein, or The formulation ensures a steady release of therapeutically effective concentrations of its pharmaceutically acceptable salt. -Tryptamine derivatives such as MeO-DMT, psilocybin, and psilocin, or and / or a pharmaceutically acceptable salt thereof, e.g., a tablet, It is formulated in an osmotic controlled release pharmaceutical composition such as a caplet or granules. tryptamine-derived agonists such as DMT, 5-MeO-DMT, psilocybin, and psilocin or any of the compounds described herein, or a pharmaceutically acceptable salt thereof (e.g., A single core layer containing a drug (e.g., as defined by other tablet formulations described herein) The fluid is surrounded by a semi-permeable membrane with or without a drug delivery orifice. Although not intended to be used exclusively in the art, these systems are well suited for the controlled delivery of active ingredients. Because the osmolality of water is used for this purpose, delivery rates are expected to be independent of gastrointestinal conditions. In combination with the novel and inventive aspects of the present disclosure, permeable asymmetric membrane technology or AMT (e.g., For example, a monolayer tablet coated with an insoluble, asymmetric microporous membrane produced by controlled phase separation. , caplets, or granules) using the methods of treatment and described herein. The formulations can be made useful in kits such as those described above.

[0836] In some embodiments of the present disclosure, the counterion is a DMT, 5 -MeO-DMT, tryptamine derivatives such as psilocybin, psilocin, or The present invention does not significantly affect the formulation of any of the compounds described, or their pharmaceutically acceptable salts. or to achieve the desired therapeutic effect described herein, i.e., tablets, caplets, Therapeutic benefits from oral pharmaceutical compositions such as tablets, capsules, gelcaps, caps or granules. have a similar steady release of effective concentrations (e.g., symptom-based), and Tryptamine derivatives such as T, psilocybin, and psilocin, or any of the compounds described herein The compounds of the present invention, or their pharmaceutically acceptable salts, are effective in producing analgesia or psychotropic effects in the presence of analgesia or psychotropic effects. DMT, 5-MeO-DMT, and psilocybin to achieve a normal toxicity spike tryptamine derivatives such as psilocin, or any of the compounds described herein or its pharmaceutically acceptable salts thereof so as not to significantly affect the potency of -MeO-DMT, tryptamine derivatives such as psilocybin, psilocin, or Any of the compounds described, or a pharmaceutically acceptable salt thereof, may be used in the form of a hydrochloride, asparagine, or the like. It may also be formulated as a pharmaceutically acceptable salt thereof, such as a phosphate or succinate. Exemplary salts within the scope include, but are not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, Acid, salts with inorganic acids such as nitric acid, perchloric acid, sulfuric acid, or phosphoric acid, e.g., methanesulfonate Sulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-thiazolinone benzenesulfonic acid, fumaric acid, oxalic acid, maleic acid, citric acid, succinic acid, tartaric acid, etc. and other mineral and carboxylic acids known to those skilled in the art. Examples include sodium, potassium, calcium, magnesium, lithium, and aluminum. salts with inorganic cations such as ammonium, zinc, and salts with inorganic cations such as ammonia, alkylamines, Hydroxyalkylamines, lysine, arginine, N-methylglucamine, procaine, etc. In certain embodiments, the salts formed with any pharmaceutically acceptable amine are A commercially acceptable salt is the hydrochloride salt.

[0837] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or and a pill-like oral administration of any one of the formulations described herein, comprising a pharmaceutically acceptable salt of DMT, 5-MeO-DMT, psilocybin ... tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and and for example, the treatment, prevention or use of a disease, disorder or condition, such as pain, as described herein. Provide instructions for use regarding administration.

[0838] In some embodiments of the present disclosure, the pain being treated is cancer pain, e.g., intractable cancer pain. do.

[0839] In some embodiments of the present disclosure, the pain treated is post-operative pain.

[0840] In some embodiments of the present disclosure, the pain treated is orthopedic pain.

[0841] In some embodiments of the present disclosure, the pain treated is back pain.

[0842] In some embodiments of the present disclosure, the pain treated is neuropathic pain.

[0843] In some embodiments of the present disclosure, the pain treated is dental pain.

[0844] In some embodiments of the present disclosure, the pain treated is chronic pain in opioid-tolerant patients. is.

[0845] In some embodiments, the disease or disorder is a disease associated with the serotonin 5-HT2 receptor. Or a disability.

[0846] In some embodiments, the disease or disorder is major depressive disorder (MDD), suicidal ideation or Major depressive disorder with suicidal behavior (MDD), suicidal ideation, suicidal behavior, non-suicidal self-injury disorder (NSI) SSID), Treatment-Resistant Depression (TRD), Post-Traumatic Stress Disorder (PTSD), Bipolar Bipolar and related disorders, including bipolar I disorder, bipolar II disorder, and cyclothymic disorder; obsessive-compulsive disorder (OCD); CD), generalized anxiety disorder (GAD), social anxiety disorder, alcohol use disorder, opioids substance use disorder, including use disorder, amphetamine use disorder, nicotine use disorder, and cocaine use disorder use disorder, anorexia nervosa, bulimia nervosa, Alzheimer's disease, cluster headaches and migraines, Attention-deficit hyperactivity disorder (ADHD), pain and neuropathic pain, aphantasia, childhood onset Fluency disorder, major neurocognitive disorder, mild neurocognitive disorder, sexual dysfunction, chronic fatigue syndrome, leukemia from the group consisting of central nervous system (CNS) disorders, including rheumatoid arthritis, obesity, or a combination thereof. In some embodiments, the disease or disorder is an alcohol use disorder.

[0847] In some embodiments, the disease or disorder comprises a condition of the autonomic nervous system (ANS).

[0848] In some embodiments, the disease or disorder includes asthma and chronic obstructive pulmonary disorder (COPD). Including lung disorders.

[0849] In some embodiments, the disease or disorder is a cardiovascular disorder, including atherosclerosis. include.

[0850] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or Oral administration, such as a pill, of any one of the formulations herein comprising a pharmaceutically acceptable salt of and pharmaceutical compositions, such as pharmaceutical compositions of tablets, containing DMT, 5-MeO-DMT, psilocybin, tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and Instructions for use in the treatment of brain injury are provided.

[0851] Some embodiments of the present disclosure include tryptophan, such as DMT, psilocybin, and psilocin. or any of the compounds described herein, or pharmaceutically acceptable salts thereof. Medications for oral administration, such as pills, of any of the formulations herein, including the soluble salts thereof. and pharmaceutical compositions, such as compositions containing DMT, 5-MeO-DMT, psilocybin, and psilocybin. a tryptamine derivative such as tryptamine, or any of the compounds described herein, or Kits for treating a subject with pharmaceutically acceptable salts thereof, and methods for treating depression and Provide instructions for use in the

[0852] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or Oral administration, such as a pill, of any one of the formulations herein comprising a pharmaceutically acceptable salt of and pharmaceutical compositions, such as pharmaceutical compositions of tablets, containing DMT, 5-MeO-DMT, psilocybin, tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and and instructions for use in the treatment of, for example, migraine with aura.

[0853] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or Oral administration, such as a pill, of any one of the formulations herein comprising a pharmaceutically acceptable salt of and pharmaceutical compositions, such as pharmaceutical compositions of tablets, containing DMT, 5-MeO-DMT, psilocybin, tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and and instructions for use in the treatment of refractory asthma.

[0854] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or Oral administration, such as a pill, of any one of the formulations herein comprising a pharmaceutically acceptable salt of and pharmaceutical compositions, such as pharmaceutical compositions of tablets, containing DMT, 5-MeO-DMT, psilocybin, tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and and instructions for use in the treatment of stroke.

[0855] Some embodiments of the present disclosure include DMT, 5-MeO-DMT, psilocybin, and psilocybin. tryptamine derivatives such as tryptamine, or any of the compounds described herein, or Oral administration, such as a pill, of any one of the formulations herein comprising a pharmaceutically acceptable salt of and pharmaceutical compositions, such as pharmaceutical compositions of tablets, containing DMT, 5-MeO-DMT, psilocybin, tryptamine derivatives such as psilocin, or compounds described herein kits for treating a subject with either the compound or a pharmaceutically acceptable salt thereof; and and instructions for use in the treatment of alcoholism.

[0856] In some embodiments, the instructions for use are an integral component of the packaging for the tablet composition. Form an element.

[0857] In embodiments, the present disclosure provides a method for treating a patient in need of treatment, such as when tryptamine therapy may be suggested, considered, or recommended. a subject diagnosed as having, suffering from, or susceptible to a disease, disorder, or condition The present invention features an oral, modified release pharmaceutical composition for oral administration to a subject for treating an elephant in need of treatment with said oral, modified release pharmaceutical composition; The thing is, (a) To treat, prevent, and / or manage a disease, disorder, or condition in a subject Triple-active compounds such as DMT, 5-MeO-DMT, psilocybin, and psilocin are used in effective doses for a methamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof drugs containing suitable salts, and (b) a pharmaceutically acceptable excipient; Upon oral administration of the modified release pharmaceutical composition to a subject, the release period of the drug from the pharmaceutical composition is During this time, the release of the drug is controlled so as not to cause a neurotoxic spike in the subject's plasma. A steady release is maintained from the prepared pharmaceutical composition.

[0858] General tablet formulations The formulations of the present disclosure include tablets, capsules, caplets, gel caps, and cap compositions. This includes any orally administered pharmaceutical composition, including uncoated tablets or or coated tablets, caplets and caps (film-coated Includes tablets with or without sugar coating, and gastro-resistant / enteric coating. Oral pharmaceutical compositions for oral use may contain a diluent, a disintegrant, a binder, a suspending agent, a suspending agent, a disintegrant ... Pharmaceutically acceptable additives such as lubricants, powder flow improvers, wetting agents, sweeteners, flavoring agents, coloring agents and preservatives. DMT, 5-MeO-DMT, psilocybin, and tryptamine derivatives such as psilocin, or any of the compounds described herein Furthermore, the oral pharmaceutical compositions of the present disclosure may be prepared in the form of, for example, a powder or granules. Solid dosage forms intended for oral administration obtained by dry granulation by single or multiple compression of In some embodiments, the oral pharmaceutical composition may be obtained using a wet granulation technique. In some embodiments, the oral pharmaceutical composition is prepared by molding, heating / annealing, or extrusion techniques. It can be obtained by surgery.

[0859] In some embodiments, the oral tablet is a right cylinder, the end faces of which are flat or convex; The edges may be beveled. In some embodiments, the surfaces are convex. may have lines or break marks (scores), symbols, or other marks. do.

[0860] In some embodiments, the break mark is a square on the tablet to provide a sub-tablet dose. In some embodiments of the present disclosure, the tablet composition comprises , diluents, binders, disintegrants, glidants, lubricants, modifying the action of active ingredients in dosage forms and in the gastrointestinal tract substances that can be used for the purpose of The active ingredient may contain one or more excipients, such as tastants. When such excipients are used, they may be present in the active ingredient. have no adverse effect on the stability, dissolution rate, bioavailability, safety or efficacy of the drug. It must be ensured that there are no incompatibilities between the components of the dosage form.

[0861] Coated tablets are made from natural or synthetic resins, polymers, gums, fillers, sugars, Plasticizers, polyols, waxes, coloring substances approved by the appropriate national or regional authorities, and A tablet coated with one or more layers of a mixture of substances such as flavorings and flavoring substances. The drug is a tryptophan derivative of DMT, 5-MeO-DMT, psilocybin, and psilocin. or any of the compounds described herein, or pharmaceutically acceptable salts thereof. The tablet does not contain any active ingredients such as soluble salts. The tablet is resistant to the matrix, air, moisture, or light. protection of the active ingredient from burst release from the They may be coated for various reasons, such as to improve appearance. The material to be applied may be applied as a solution or suspension.

[0862] In some embodiments, the manufacturing process for oral pharmaceutical compositions, such as tablets, is in accordance with Good Manufacturing Practices. In some embodiments, the oral pharmaceutical composition may be manufactured by: The mixing with the excipients is carried out in a manner that ensures homogeneity. The oral pharmaceutical composition may be prepared by, for example, coating, preserving, and have adequate mechanical strength to avoid crushing or breaking during subsequent processing such as distribution ensure that the active ingredient is not degraded; minimize the risk of microbial contamination; Furthermore, it is intended to be split to provide sub-tablet doses. In the manufacture of divided tablets (tablets with a divided mark or multiple marks) that are Division with respect to uniformity of mass or content of divided parts so that the product receives the intended dose Steps will be taken, as necessary, to ensure the validity of the mark.

[0863] Generally, suitable doses range from, for example, about 0.1 to about 5 mg per kilogram of body weight per day. such as in the range of about 0.01 to about 100 mg per kilogram of body weight of the recipient per day. Additional details regarding formulation and administration techniques can be found in the scientific literature and It is described in detail in the patent literature, e.g., Remington's Pharmaceuticals utical Sciences, Maack Publishing Co, East See the latest issue of Remington's on Pa. ("Remington's"). Once formulated into a suitable carrier, it is placed in a suitable container and used for the treatment of the indicated condition. Any of the compounds described herein (DMT, 5-MeO-D Tryptamine derivatives such as MT, psilocybin, and psilocin, or any of the compounds described herein administration of a formulation containing any of the compounds described herein, or a pharmaceutically acceptable salt thereof; For example, such labeling may include information regarding the amount, frequency, method of administration, treatment regimen, and symptoms. Includes instructions to:

[0864] Monograph Compliance

[0865] In some embodiments, the formulations of the present disclosure are In particular, the formulations of the present disclosure conform to certain industry-recognized monographs. Acceptable under inspection, mass uniformity analysis, content uniformity analysis, and / or dissolution / disintegration analysis are considered possible, all of which are established by the relevant monographs.

[0866] In some embodiments, a procedure is performed throughout manufacturing to ensure proper in-process controls are in place. These are designed to ensure the effectiveness of each stage of manufacturing. In-process controls during tablet manufacturing include the moisture content of the final lubricant mixture, granule size, and , the flow of the final mixture, and, where relevant, the uniformity of the tablet core mass before coating. In-process controls during tablet manufacturing also include the consistency of the dimensions (thickness, diameter), mass, etc. of the final dosage form. consistency, hardness and / or crushing force, friability, disintegration, or dissolution rate (e.g., modified release Suitable test methods that may be used to demonstrate these properties include: It is known in the art.

[0867] In some embodiments, the packaging may protect the pharmaceutical composition, including the tablet, from light, moisture, and other elements during transportation. and may or may be required to be suitable to protect against damage.

[0868] In additional embodiments, the commercially available formulation (e.g., kit) is manufactured according to Good Manufacturing Practice (GMP) regulations. Comply with all established signage requirements, including the following: (1) Name of the drug (2) Name of the active ingredient: The International Nonproprietary Name (INN) should be used whenever possible. . (3) The amount of active ingredient in each tablet and the number of tablets in the container (4) Batch (lot) number assigned by the manufacturer (5) Expiration date and, if necessary, manufacturing date (6) Any special storage conditions or handling precautions that may be required. (7) Any instructions for use, warnings, and precautions that may be required. (8) The name and address of the manufacturer or person responsible for marketing the product. (9) For divided tablets, the directions for use include divisions to provide doses less than one tablet, the label shall not include: The storage conditions and duration of use of those parts that are not immediately collected or administered shall also be included. It won't happen.

[0869] In some embodiments, a pharmaceutical composition such as a tablet can be packaged and stored without losing its integrity. and be able to withstand handling, including transportation.

[0870] The formulations of the present disclosure can be used in the methods of the present disclosure, such as the therapeutic methods of the present disclosure. Thus, the present disclosure provides methods for the treatment of DMT, 5-MeO-DMT, and cyclosporin, for example, for the treatment of pain. tryptamine derivatives such as psilocin, and psilocin, or any of the compounds described herein or a pharmaceutically acceptable salt thereof. Therefore, in some embodiments, the present disclosure relates to methods of using different species of and providing a method for the management of various types of pain, including the management of intractable cancer pain, neuralgia, surgical pain, and the like, as described herein. pain after the injury, complex regional pain syndrome (CRPS), e.g., migraine with aura, and depression , alcoholism, intractable asthma, epilepsy, acute brain injury and stroke, Alzheimer's disease, and other conditions, including but not limited to, other disorders, including oral administration of the formulations of the present disclosure. In some embodiments, the use of the formulations of the present disclosure may be used as the sole therapy. In some embodiments, the use of the formulations of the present disclosure may be used as adjuvant / combination therapy. .

[0871] In some embodiments, the present disclosure provides for the management of different types of pain, including, for example: Cancer pain, including intractable cancer pain, neuropathic pain, opioid-induced hyperalgesia, and opioids Associated intolerance, neuralgia, post-operative / post-surgical pain, Complex Regional Pain Syndrome (CRPS), shock , limb amputations, severe chemical or thermal burns, sprains, torn ligaments, fractures, wounds, and other injuries. Tissue damage Dental surgery, procedures, and illnesses Labor and delivery, during physiotherapy, radiation poisoning, after Allergic Recurrent Immune Deficiency Syndrome (AIDS), epidural (or epidural) fibrosis, orthopedic pain, back pain Pain, failed back surgery and failed laminectomy, sciatica, painful sickle cell crisis , arthritis, autoimmune diseases, intractable bladder pain, e.g., shingles pain or herpes pain pain associated with certain viruses, such as nausea, acute nausea, e.g., pain that can cause nausea abdominal pain, often accompanied by severe nausea, migraine with aura, and depression ( For example, acute or chronic depression, depression accompanied by pain, alcoholism, acute agitation , refractory asthma, acute asthma (e.g., unrelated pain conditions may precipitate asthma), Other conditions, including epilepsy, acute brain injury and stroke, Alzheimer's disease and other disorders Additionally, the present disclosure provides a method for treating these types of pain or conditions. Includes any combination of treatment / management.

[0872] In some embodiments, the pain being treated / managed is acute breakthrough pain or chronic pain conditions. This is pain associated with winding up that can occur in this condition.

[0873] In some embodiments of the present disclosure, the pain being treated / managed is cancer pain, e.g., intractable cancer pain. It's pain.

[0874] In some embodiments of the present disclosure, the pain being treated / managed is post-operative pain.

[0875] In some embodiments of the present disclosure, the pain being treated / managed is orthopedic pain.

[0876] In some embodiments of the present disclosure, the pain being treated / managed is back pain.

[0877] In some embodiments of the present disclosure, the pain being treated / managed is neuropathic pain.

[0878] In some embodiments of the present disclosure, the pain being treated / managed is dental pain.

[0879] In some embodiments of the present disclosure, the condition being treated / managed is depression.

[0880] In some embodiments of the present disclosure, the pain treated / managed is pain in opioid-tolerant patients. It is chronic pain.

[0881] In embodiments, the present disclosure provides a method for treating a disease or condition by modulating NMDA activity. The method relates to a method of treating a patient with any of the compounds described herein (e.g., DMT, 5-M Tryptamine derivatives such as eO-DMT, psilocybin, and psilocin, or The method comprises administering an effective amount of a compound according to any one of the preceding claims to a subject in need thereof. In embodiments, the disease or condition is levodopa-induced dyskinesia, dementia (e.g., alopecia), Zheimer's dementia), tinnitus, treatment-resistant depression (TRD), major depressive disorder, neuropathic Pain, agitation due to or associated with Alzheimer's disease, pseudobulbar effect, autism, ocular function , generalized anxiety disorder, Alzheimer's disease, schizophrenia, diabetic neuropathy, acute pain, depression illness, bipolar depression, suicidal tendencies, neuropathic pain, or post-traumatic stress disorder (PTSD) In embodiments, the disease or condition is selected from a psychiatric disorder or mental disorder (e.g., For example, schizophrenia, mood disorders, substance-induced psychosis, major depressive disorder (MDD), and bipolar disorder , bipolar depression (BDep), post-traumatic stress disorder (PTSD), suicidal ideation, anxiety, Obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD). The disease or condition can be a neurological disorder (e.g., Huntington's disease (HD), Alzheimer's disease (AD), or (AD), or systemic lupus erythematosus (SLE).

[0882] For example, in some embodiments, the present disclosure provides a method for treating rheumatoid arthritis, including treating rheumatoid arthritis with DMT, 5-MeO-DMT, psilocybin, and tryptamine derivatives such as psilocin, or any of the compounds described herein. or a pharmaceutically acceptable salt thereof, These include tryptamine derivatives such as DMT, 5-MeO-DMT, psilocybin, and psilocin. or any of the compounds described herein, or a pharmaceutically acceptable salt thereof. an orally administered tablet composition described in the present disclosure, such as a matrix composition comprising A step of administering to a patient is included such that the subject is treated.

[0883] The administering physician may prescribe a DMT, Tryptamine derivatives such as 5-MeO-DMT, psilocybin, and psilocin, or The amount and type of any of the compounds described herein, or a pharmaceutically acceptable salt thereof, By modulating the timing of the treatment, prophylactic or therapeutic treatments can be provided. .

[0884] In some embodiments, the present disclosure provides a method for producing a tablet composition, such as a monolayer tablet composition, comprising: Tryptamine derivatives such as MT, 5-MeO-DMT, psilocybin, and psilocin, or any of the compounds described herein, or pharmaceutically acceptable salts thereof. A steady release of effective concentrations of DMT, 5-MeO-D, and 5-MeO-D was achieved from the oral tablet over the complete release period. Tryptamine derivatives such as MT, psilocybin, and psilocin, or any of the compounds described herein analgesic or A monolayer tablet that provides a drug without neurologically toxic spikes, such as psychotic toxic spikes. Drugs such as DMT, 5-MeO-DMT, psilocybin, and psilocin are administered in tablets containing a liptamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof and providing a method for oral continuous administration of acceptable salts of DMT, 5-MeO-DMT, scyllo. tryptamine derivatives such as psilocin, and psilocin, or compounds described herein or a pharmaceutically acceptable salt thereof. The present invention provides a method for orally administering a tablet composition to a subject, such that the tablet composition

[0885] In some embodiments of the present disclosure, the subject is a mammal.

[0886] In some embodiments of the present disclosure, the mammal is a human.

[0887] In some embodiments, the present disclosure provides a method for treating DMT, 5-MeO-DMT, psilocybin, and psilocybin-related disorders. a tryptamine derivative such as rosin, or any of the compounds described herein, toxic spikes in the plasma concentration of its pharmaceutically acceptable salts resulting in analgesic or psychotomimetic events Oral formulations without the neurotoxic spikes of DMT, 5-MeO-DM Tryptamine derivatives such as T, psilocybin, and psilocin, or any of the compounds described herein and ensuring a steady release of therapeutically effective concentrations of any of the compounds listed in claim 1 or a pharmaceutically acceptable salt thereof. To achieve this, triphosphatase inhibitors such as DMT, 5-MeO-DMT, psilocybin, and psilocin a methamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof In some embodiments, the method includes: (i) preparing a water-insoluble salt of (ii) a polymer bearing one or more negatively charged groups; and (iii) DMT, 5-, e.g., to produce a monolayer orally administered tablet composition. Tryptamine derivatives such as MeO-DMT, psilocybin, and psilocin, or or a pharmaceutically acceptable salt thereof. In some embodiments, the method includes (i) a polymeric polymer comprising HPMC, e.g., about 2,000 and (ii) polyethylene oxide (PEO), such as a MW of about 7,000 KDa. tryptamine derivatives such as DMT, 5-MeO-DMT, psilocybin, and psilocin, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof. combining to produce an orally administered, e.g., monolayer, tablet composition; In some embodiments, the method comprises: and tryptamine derivatives such as DMT, 5-MeO-DMT, psilocybin, and psilocin. or any of the compounds described herein, or a pharmaceutically acceptable salt thereof. The tablet composition includes a step of combining a polyethylene glycol (PEG) such as PEG8K. Polyethylene glycol (PEG), poly(acrylic acid), etc., which carry one or more negatively charged groups. and / or further heating / annealing, e.g., under extrusion conditions. In some embodiments, the formulations of the present disclosure may be administered in the presence of: It may also be administered in combination with other active therapeutic agents, such as opioids. Therefore, the formulations of the present disclosure help reduce the amount of opioids required to treat a patient. tsu.

[0888] In some embodiments, the formulations of the present disclosure are not administered in combination with other active therapeutic agents.

[0889] In some embodiments, the formulations of the present disclosure may be combined with another formulation of tryptamine or a derivative thereof, e.g. For example, it may be administered in combination with a fast-release formulation of tryptamine or a derivative thereof.

[0890] In some embodiments, the present disclosure provides a method for treating DMT, 5-MeO-DMT, psilocybin, and psilocybin-related disorders. a tryptamine derivative such as rosin, or any of the compounds described herein, toxic spikes in the plasma concentration of its pharmaceutically acceptable salts resulting in analgesic or psychotomimetic events DMT, 5-MeO-DMT, psilocybin, and psilocin from oral formulations without or any of the compounds described herein, or To ensure steady release of therapeutically effective concentrations of pharmaceutically acceptable salts, DMT, 5-Me Tryptamine derivatives such as O-DMT, psilocybin, and psilocin, or Methods for formulating any of the compounds described, or a pharmaceutically acceptable salt thereof, are provided. The method involves the use of triphosphatase inhibitors such as DMT, 5-MeO-DMT, psilocybin, and psilocin. a methamine derivative, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof These formulations include the formulation of DMT, 5-MeO-D, and other salts into osmotic controlled-release tablets. tryptamine derivatives such as MT, psilocybin, and psilocin, or the compounds described herein A single core layer containing either of the compounds, or a pharmaceutically acceptable salt thereof, is used as a drug delivery agent. In some embodiments, the membrane is surrounded by a semi-permeable membrane, which may or may not have an orifice. The novel and unique pharmaceutical compositions of the present disclosure (DMT, 5-MeO-DMT, psilocybin, psilocybin) a tryptamine derivative such as rosin, or any of the compounds described herein, or a pharmaceutically acceptable salt thereof) and permeable asymmetric membrane technology or AMT (e.g. coated with an insoluble, asymmetric microporous membrane produced by controlled phase separation (technology directed to monolayer tablets) as useful in the methods and kits described herein. A useful formulation can be prepared. [Example]

[0891] Example 1. Synthesis of PI-α,α-d2 The synthesis of PI-α,α-d2 was carried out by iminoformamide synthesis using formaldehyde / dimethylamine. was then converted to the 3-acetic acid derivative using potassium cyanide under acidic conditions. Starting with 4-oxybenzylindole, thionyl chloride and dimethylamine were used. Subsequent treatment yields the related amide, which is reduced with LiAlD4, which is located at the α-position. In the final step, the -OBz ​​protecting group is removed using a palladium catalyst. The product is then removed by hydrogen gas to produce the final compound. 1 HNM Confirmed by R and LC-MS. [ka]

[0892] Example 2. DMT-d 10 Synthesis of DMT-d 10 The synthesis of Starting with an indole, which is converted to the related amide by treatment with diaminodiamine-d6, Subsequent reduction with LiAlD4 leads to the final product. The structure of the material is 1 HN Confirmed by MR and LC-MS.

[0893] Example 3. Synthesis of 5-CD3O-DMP-α,α,5,5,5-d5

[0894] The synthesis of 5-CD3O-DMP-α,α,5,5,5-d5 was carried out using deuterated methyl iodide. 5-Deuterated methoxyindoles prepared by methylation of 5-hydroxyindoles using This was carried out similarly to DMT-α,α-d2 described in Example 2, starting with dhol. The structure of the product is 1 Confirmed by 1 H NMR and LC-MS.

[0895] Example 4. Synthesis of Aer-α,α,-d2

[0896] -OBz bis-deuterated tryptamine intermediate obtained as described in Example 1 The synthesis of Aer-α,α-d2 was carried out using the above method. The material was treated with methylamine to give alkyl and then reduced with hydrogen over palladium to give the final product as the iodide salt. (Scheme 2). The structure of the product is: 1 Confirmed by 1 H NMR and LC-MS. [ka]

[0897] Example 5. 5-HT Receptor Pharmacology Binding affinity (K i ) and functional ability (EC 50 ) value, These are summarized in Table 1. Deuteration has little effect on affinity and function at key receptor targets. It turned out that it didn't make a sound.

[0898] Receptor affinity assay: 5-HT 1A , 5-HT 2(A、B、C) Receptor affinity, The binding of serotonergic receptors to CHO-K1 cells was determined by competitive binding of serotonergic ligands. Collect membranes from HEK293 cells or HEK293 cells and inject radioligand K d Concentration of assay buffer After equilibration, the ligand was incubated in a broth and tested for compounds that compete for the receptor binding site. -Receptor-membrane complex (Microbeta, PerkinElmer) was collected. The reaction was terminated by this and the readings were counted in a scintillation counter (Microbeta2, Perk Radioactivity was measured by a chromatograph (inElmer). Data were fitted with a nonlinear curve and the K i The value is C was calculated according to the Heng-Prusoff equation.

[0899] Receptor Functional Assay: 5-HT 1A Receptor-mediated Gi stimulation (cyclic adenosine monophosphate ( Decreased levels of cAMP) and 5-HT 2(A、B、C) Receptor-mediated Gq stimulation (Inno Phosphoinositide hydrolysis leading to the production of inositol phosphate 1 (IP1) - standard signaling pathways—e.g., homogeneous time-resolved fluorescence (HTRF)-enabled microplates with a fluorescent detector (e.g., Mithras LB 940, Berthold). Resonance Energy Transfer (FRET) technology (e.g., LANCE Ultra cAMP T R-FRET (PerkinElmer) and IP-One HTRF (Cisbio ) kit) was measured as previously described (Canal et al., 201 Briefly, CHO-K1 cells or H cells expressing serotonergic receptors were cultured in vitro. EK293 cells were incubated with test compounds in stimulation buffer. After equilibration, the reaction was monitored by lysis. Terminate with fluorescent conjugates of donor and acceptor in buffer and measure FRET Data were collected to assess efficacy (e.g., EC 50 ) and efficacy (e.g., E MAX ) was fitted with a nonlinear curve to calculate the [Table 1]

[0900] Example 6. In vitro hepatic metabolism and kinetics Deuterium isotope effect 5-MeO-DMT and 5-MeO-DMT-α,α-d (10 μl of 2 μM solution) ) in 100 mg rat liver microsomes, NADPH regenerating system (1 mM NADP, 1 unit / ml isocitrate dehydrogenase, 5 mM isocitrate, 5 mM magnesium chloride In 200 μl of medium consisting of 25 mM phosphate buffer (pH 7.4), The reaction was stopped at different time points by adding 300 μl of acetonitrile. (0-60 min) was completed. For product analysis, precipitated salts and proteins were removed by centrifugation. The remaining solution was diluted with 300 μl of water and analyzed by LC / MS (ABS Sc Agilent iex 4000 QTRAP LC / MS / MS mass spectrometer interfaced The metabolic stability was assessed by assessing the rate of disappearance of the major parent peak. The observed overall kinetic deuterium isotope effect (deuterated vs. non-deuterated molecules) The reduction in the reaction rate of hydrogenated molecules was substantial, ranging from 150 to 200%. This assay for MT-α, α-d2 and DMT-α, α, β, β-d4 was similar. The effects of DMT-d 10 Further enhancement of metabolic stability of It showed superiority in the MAO-A enzyme assay and further demonstrated the -N(CD3)2 substituent The deuteration effect is emphasized. [Table 2] [Table 3] [Table 4] [Table 5]

[0901] Example 7. PK studies in rats and mice Key PK parameters (expressed as percentage changes relative to undeuterated material) The half-life (T 1 / 2 ), area under the curve (AUC), bioavailability (F), and The pharmacokinetics of deuterated tryptamine was studied in rats, including the blood plasma ratio (BPR). In a typical experiment, the cassette administration was performed via a surgically inserted jugular vein catheter (Cha). Five Wistars (Willows River, Andover, Massachusetts) Two groups of female rats (200-250 g) were fasted for 12 hours and then administered 5 mg / kg Deuterated analogs of 100 mg / kg and related non-deuterated analogs at 5 mg / kg were administered by oral gavage. The drugs were administered to each group via the catheter or at 0, 15, 30, 60 minutes and 2, Plasma obtained at 4, 8, and 24 hours was analyzed for parent molecules using LC / MS spectroscopy. Two separate groups of five animals were used to determine the blood-to-plasma ratio (BPR). Each group was sacrificed at 15 and 30 minutes, respectively, and the concentration of the parent drug was determined at LC in brain and plasma by I / MS spectroscopy. [Table 6]

[0902] Example 8. In vitro enzyme assay The metabolic consequences of selective deuteration of tryptamine-based compounds were investigated using two in vitro assays: Monoamine oxidase A (MAO-A) and rat liver microsomes (RLM) ) was confirmed. The rat liver microsome assay revealed that tryptamine is involved in the metabolic fate of tryptamine. It is considered a good proxy for in vivo hepatic metabolism. Similar deuteration results were detected in in vitro assays.

[0903] Without being bound by any particular theory, tryptamines, particularly tryptamine The major metabolic degradation pathway involving the exocyclic side chain of is hypothesized to be controlled by MAO-A enzymes. Thus, for some molecules, the outer ring of tryptamine (e.g., the N-CH2 fragment) Specific deuteration in the formula moiety is important for overall metabolic behavior, i.e., the triglycerides discussed herein. It is believed that this can have a significant effect on the significant delay in enzymatic degradation of glutamine derivatives. In these examples, the MAO-A and RLM assays showed significantly higher cytotoxicity compared to the base non-deuterated compound. Increased metabolic stability was observed in both the N-CH2 group and the hydroxylase in the absence of MAO-A metabolism. Deuteration did not affect the kinetics of RLM digestion. No metabolism was observed.

[0904] The results establish a set of exemplary compounds suitable for selective deuteration of the N-CH2 fragment. The results are summarized in Table 7, which also provides additional information on selective deuteration in other parts of the molecule. Comparisons between compounds were based on half-life, i.e., the time it takes for 50% of the compound to be digested in the assay. A best fit curve was used to calculate the time points.

[0905] hrMAO-A (Lot No. 8213001) and hrMAO control (Lot No. 10 67001) was purchased from XenoTech. The reaction mixture was prepared as follows: Co-administration TA was added to the reaction mixture at a final concentration of 1 μM each. Kynuramine (25 microM) was run simultaneously with TA in a separate reaction. (without TA or kynuramine) was equilibrated at 37°C for 5 minutes in a shaking water bath. The reaction is initiated by the addition of TA or kynuramine, and the mixture is incubated at 37°C in a shaking water bath. Aliquots (100 microliters) of the TA reaction mixture were added at 0, 5, 10, and 2 Aliquots of the positive control reaction mixture (100 Microliters (µL) were collected at 0 and 30 minutes. TA and kynuramine samples were diluted with 0.1% Immediately combine with 100 microL of ice-cold 100% MeCN containing formic acid and IS. The reaction was terminated by centrifugation. The sample was then mixed and centrifuged to precipitate the proteins. All TA samples were assayed by LC-HRAMS. R (sample to IS) was compared to the PARR at time 0 and the percent remaining at each time point. The reaction composition was determined as follows: hrMAO 0.02 mg / mL, potassium phosphate, pH 7.4 100 mM, magnesium chloride 5 mM, test substance (each) 1 microM.

[0906] The substrate was 100 mg rat liver microsomes, an NADPH-regenerating system (1 mM NADP, 1 Units / ml Isocitrate Dehydrogenase, 5mM Isocitrate, 5mM Magnesium Chloride nesium), and 200 μl of medium consisting of 25 mM phosphate buffer (pH 7.4) The reactions were incubated in different The analysis was completed at the following time points (0, 5, 10, 20, 30, 60, and 120 min). To remove precipitated salts and proteins, spin out the remaining solution in a centrifuge and The samples were diluted with 1 μL of water and analyzed by LC / MS (ABS Sciex 4000 QTRAP LC / MS) The samples were injected into an Agilent 1200 system interfaced with a S / MS mass spectrometer. Stability was estimated by assessing the rate of disappearance of the major parent peak. [Table 7] [Table 8]

[0907] Tryptamine-based substrates with N-Me and N-Et substituents, as seen in Table 7, and MAO- for asymmetrically substituted substrates such as N,N-Me, Et substituents. A metabolically active, but not MAO-, for tryptamine substrates containing the N,N-Et moiety. No metabolic activity of A was observed. As a result, for example, i-Pr and allylic, -NC H2-CH2 and deuterium in N-R8,R9 fragments, etc. Tryptamine-based substrates with hydroxyl chains are substituted in both MAO-A and RLM assays. No adverse effects were observed. Tetradeuteration of deuteration enhances the metabolic activity of its base undeuterated substrate, i.e., enzymatic degradation. The N-R8,R9 fragment stabilized the substrate against MAO-A action compared to the N-R8,R9 fragment. Hydrogenation further stabilized the substrate against MAO-A attack, as shown in Table 7. Deuterated DMT-d 15 per phenyl ring due to additional deuteration 、 RLM Up Selective deuteration at the exocyclic moiety observed in DMT-d 10 Compared to the half-life However, deuteration of the phenyl ring did not improve MAO-A metabolism. It has been observed that tryptamine plays a role in slowing down the RLM metabolism. Without being bound by any particular theory, it is believed that CYP isoforms other than MAO Enzymatic contribution to the metabolism of tryptamine substrates, producing ring-hydroxylated metabolites The involvement of CYP enzymes is thought to be related to the difference between deuterated 5-OMe and non-deuterated 5-OMe substituted cytochrome P450. It is also thought to be involved in the delayed RLM metabolism of liptamine.

[0908] All patents, patent applications, and other scientific or The technical literature is incorporated herein by reference in its entirety. The embodiments described herein may include any element or elements specifically or non-specifically disclosed herein. It can be properly practiced in the absence of any element, limitation, or limitations. Thus, for example, in each instance herein, while retaining its ordinary meaning: The terms "comprising," "consisting essentially of," and "consisting of" are interchangeable with the other two terms. The terms and expressions used are not limiting and may be replaced by any of the following: used as terms of description and in the use of such terms and expressions There is no intention to exclude any equivalents of the features or portions thereof, and various modifications may be made to the claimed invention. It is recognized that the present methods and compositions are capable of being used in a wide range of applications. While specifically disclosed by the various features and optional features, modifications and variations of the concepts of this disclosure will occur to those skilled in the art. and such modifications and variations are within the scope of the description and the appended claims. It is to be understood that these are considered to be within the scope of the compositions and methods defined.

[0909] Any single term, single element, single phrase, group of terms, or phrase described herein Each group or group of elements may be specifically excluded from the claims.

[0910] For example, ranges such as temperature ranges, time ranges, composition ranges, or concentration ranges may be provided herein. If a range is given, all intermediate and subranges and all individuals within the given range are included. Any range or ranges within the description herein are intended to be included within the present disclosure. Any subrange or individual value within a subrange may be excluded from the scope of the present invention. It will be understood that any element or It is understood that steps may be excluded from the claimed compositions or methods.

[0911] Additionally, features or aspects of the compositions and methods may be incorporated into other Markush groups or alternatives. When described in terms of a grouping of compounds, one of skill in the art will recognize that compositions and methods also Thus, any individual member or members of the Markush Group or any other group You will recognize that the information is described in terms of a subgroup of the

[0912] Accordingly, the foregoing merely illustrates the principles of the methods and compositions. Although not explicitly described or shown herein, it embodies the principles of the present disclosure and incorporates the spirit and scope of the present invention. It is to be understood that various arrangements can be devised that fall within the scope of the invention. All examples and conditional language recited herein are within the scope of the principles of the present disclosure and the art. To assist the reader in understanding the concepts contributed by the inventors to the advancement of It is intended primarily and not to be construed as being limited to such specifically recited examples and conditions. Furthermore, the principles, aspects, and embodiments of the present disclosure and their specific implementations should be understood as being within the scope of the present invention. All statements herein reciting embodiments encompass both structural and functional equivalents thereof. Additionally, such equivalents include both currently known equivalents and those developed in the future. and equivalents thereof, i.e., any element developed that performs the same function, regardless of structure. Accordingly, the scope of the present disclosure is intended to encompass all of the compounds and methods set forth herein. The present disclosure is not intended to be limited to the illustrative embodiments shown. The spirit is embodied in the following:

Claims

1. A compound according to formula (III): 【Chemistry 1】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: X １ and X ２ is deuterium, Y １ and Y ２ is hydrogen or deuterium, R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ４ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy; R ５ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, and phosphoryloxy; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ４ is hydroxyl, and R ２ , R ５ , R ６ , and R ７ are all hydrogen In this case, R ８ and R ９ Both are -CD ３ rather than and R ２ , R ４ , R ５ , R ６ , and R ７ are all hydrogen, then R ８ and R ９ both and unsubstituted methyl, the compound or its optically pure stereoisomer, pharmaceutically acceptable Possible salts, solvates, or prodrugs.

2. R ４ is hydroxyl, R ９ The compound of claim 1 , wherein is hydrogen.

3. R ４ is hydroxyl, R ９ The compound of claim 1 , wherein is deuterium.

4. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 2. The compound of claim 1, wherein the compound is selected from deuterated methyl or ethyl.

5. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl The compound of claim 1, wherein

6. A compound according to formula (III-a): 【Chemistry 2】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ４ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy; R ５ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, and phosphoryloxy; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ４ is hydroxyl, and R ２ , R ５ , R ６ , and R ７ are all hydrogen In this case, R ８ and R ９ Both are -CD ３ rather than and R ２ , R ４ , R ５ , R ６ , and R ７ are all hydrogen, then R ８ and R ９ both and unsubstituted methyl, the compound or its optically pure stereoisomer, pharmaceutically acceptable Possible salts, solvates, or prodrugs.

7. R ４ is hydroxyl, R ９ is hydrogen or deuterium. Compound.

8. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 7. The compound of claim 6, wherein the compound is selected from deuterated methyl or ethyl.

9. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl The compound of claim 6, wherein

10. A compound according to formula (III-b): 【Transformation 3】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ２ , R ６ , and R ７ When all are hydrogen, R ８ and R ９ are both non The compound or its optically pure stereoisomer, pharmaceutically acceptable, is not a substituted methyl. Salts, solvates, or prodrugs.

11. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 11. The compound of claim 10, selected from deuterated methyl or ethyl.

12. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl The compound of claim 10, wherein

13. A compound according to formula (III-c): 【Chemistry 4】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

14. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 14. The compound of claim 13, selected from deuterated methyl or ethyl.

15. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 14. The compound of claim 13, wherein

16. A compound according to formula (III-d): 【Transformation 5】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ２ , R ６ , and R ７ When all are hydrogen, R ８ and R ９ are both- CD ３ a compound or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, solvates, or prodrugs.

17. R ９ 17. The compound of claim 16, wherein is hydrogen.

18. R ９ 17. The compound of claim 16, wherein is deuterium.

19. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 17. The compound of claim 16, wherein the compound is selected from deuterated methyl or ethyl.

20. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 17. The compound of claim 16, wherein

21. A compound according to formula (III-e): 【Transformation 6】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

22. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 22. The compound of claim 21, selected from deuterated methyl or ethyl.

23. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 22. The compound of claim 21, wherein

24. A compound according to formula (III-f): 【Transformation 7】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

25. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 25. The compound of claim 24, selected from deuterated methyl or ethyl.

26. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 25. The compound of claim 24, wherein

27. A compound according to formula (III-g): 【Transformation 8】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

28. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 28. The compound of claim 27, selected from deuterated methyl or ethyl.

29. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 28. The compound of claim 27, wherein

30. A compound according to formula (III-h): 【Chemistry 9】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

31. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 31. The compound of claim 30, selected from deuterated methyl or ethyl.

32. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 31. The compound of claim 30, wherein

33. A compound according to formula (III-i): 【Chemistry 10】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

34. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 34. The compound of claim 33, selected from deuterated methyl or ethyl.

35. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 34. The compound of claim 33, wherein

36. A compound according to formula (III-j): 【Chemistry 11】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

37. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 37. The compound of claim 36, selected from deuterated methyl or ethyl.

38. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 37. The compound of claim 36, wherein

39. A compound according to formula (III-k): 【Chemistry 12】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ４ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, unsubstituted or substituted acetoxy, and phosphoryloxy; R ５ are independently hydrogen, deuterium, hydroxyl, unsubstituted or substituted alkoxy, and phosphoryloxy; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ４ is hydroxyl, and R ２ , R ５ , R ６ , and R ７ are all hydrogen In this case, R ８ and R ９ Both are -CD ３ rather than and R ２ , R ４ , R ５ , R ６ , and R ７ are all hydrogen, then R ８ and R ９ both and unsubstituted methyl, the compound or its optically pure stereoisomer, pharmaceutically acceptable Possible salts, solvates, or prodrugs.

40. R ４ is hydroxyl, R ９ is hydrogen or deuterium. compound.

41. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 40. The compound of claim 39, selected from deuterated methyl or ethyl.

42. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 40. The compound of claim 39, wherein

43. A compound according to formula (III-1): 【Chemistry 13】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ２ , R ６ , and R ７ When all are hydrogen, R ８ and R ９ are both non The compound or its optically pure stereoisomer, pharmaceutically acceptable, is not a substituted methyl. Salts, solvates, or prodrugs.

44. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 44. The compound of claim 43, selected from deuterated methyl or ethyl.

45. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 44. The compound of claim 43, wherein

46. A compound according to formula (III-m): 【Chemistry 14】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

47. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 47. The compound of claim 46, selected from deuterated methyl or ethyl.

48. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 47. The compound of claim 46, wherein

49. A compound according to formula (III-n): 【Chemistry 15】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl methyl or ethyl, However, R ２ , R ６ , and R ７ When all are hydrogen, R ８ and R ９ are both- CD ３ a compound or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, solvates, or prodrugs.

50. R ９ 50. The compound of claim 49, wherein is hydrogen.

51. R ９ 50. The compound of claim 49, wherein is deuterium.

52. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 50. The compound of claim 49, selected from deuterated methyl or ethyl.

53. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 50. The compound of claim 49, wherein

54. A compound according to formula (III-o): 【Chemistry 16】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

55. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 55. The compound of claim 54, selected from deuterated methyl or ethyl.

56. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 55. The compound of claim 54, wherein

57. A compound according to formula (III-p): 【Chemistry 17】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

58. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 58. The compound of claim 57, selected from deuterated methyl or ethyl.

59. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 58. The compound of claim 57, wherein

60. A compound according to formula (III-q): [Chemistry 18] or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

61. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 61. The compound of claim 60, selected from deuterated methyl or ethyl.

62. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 61. The compound of claim 60, wherein

63. A compound according to formula (III-r): 【Chemistry 19】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

64. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 64. The compound of claim 63, selected from deuterated methyl or ethyl.

65. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 64. The compound of claim 63, wherein

66. A compound according to formula (III-s): 【Chemistry 20】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted or partially or fully deuterated methyl or ethyl , and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

67. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 67. The compound of claim 66, selected from deuterated methyl or ethyl.

68. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 67. The compound of claim 66, wherein

69. A compound according to formula (III-t): 【Chemistry 21】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted or partially or fully deuterated methyl or ethyl , and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

70. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 70. The compound of claim 69, selected from deuterated methyl or ethyl.

71. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 70. The compound of claim 69, wherein

72. A compound according to formula (III-u): 【Chemistry 22】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted or partially or fully deuterated methyl or ethyl , and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

73. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 73. The compound of claim 72, selected from deuterated methyl or ethyl.

74. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 73. The compound of claim 72, wherein

75. A compound according to formula (III-v): 【Chemistry 23】 or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt, solvate, or proton thereof. A drug, comprising: R ２ are independently hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl , unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cyclo alkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl; R ６ and R ７ is selected from hydrogen, deuterium, and halogen; R ８ is unsubstituted, partially or fully deuterated methyl or ethyl, and R ９ is hydrogen, deuterium, or unsubstituted or partially or fully deuterated methyl or an optically pure stereoisomer thereof, a pharmaceutically acceptable salt thereof, A suitable salt, solvate, or prodrug.

76. R ２ are independently hydrogen, deuterium, halogen, and unsubstituted or partially or completely 76. The compound of claim 75, selected from deuterated methyl or ethyl.

77. R ８ and R ９ are both unsubstituted or partially or fully deuterated ethyl 76. The compound of claim 75, wherein

78. A compound which is as follows: 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemistry 27】

79. A compound of the following structure: 【Chemistry 28】

80. The compound is a serotonin 5-HT ２ 80. Any of claims 1 to 79 which is an agonist of a receptor. The compound according to any one of claims 1 to 4.

81. The compound is a serotonin 5-HT ２Ａ 81. The compound according to claim 1, which is an agonist of a receptor. The compound according to any one of claims 1 to 4.

82. A compound according to any one of claims 1 to 81 and a pharmaceutically acceptable excipient. , pharmaceutical compositions.

83. 82. A method of treating a subject having a disease or disorder comprising administering to a subject a compound according to any one of claims 1 to 81. administering to said subject a therapeutically effective amount of a compound of formula (I)

84. 82. A method of treating a subject having a disease or disorder comprising administering to a subject a compound according to any one of claims 1 to 81. administering to said subject a therapeutically effective amount of a compound according to To treat, a method.

85. Serotonin 5-HT ２ In a method of treating a subject having a disease or disorder associated with a receptor 82. A method for treating a rheumatoid arthritis comprising administering to said subject a therapeutically effective amount of a compound according to any one of claims 1 to 81. The method includes:

86. The disease or disorder is a neuropsychiatric disease or disorder, or an inflammatory disease or disorder.

86. The method of any one of claims 83 to 85, wherein the disorder is

87. The disease or disorder is selected from the group consisting of post-traumatic stress disorder (PTSD), major depressive disorder (MD), D), treatment-resistant depression (TRD), bipolar I disorder, bipolar II disorder, and cyclothymic disorder including bipolar and related disorders, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), Anxiety disorder, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine Substance use disorders, including use disorders and cocaine use disorders, anorexia nervosa, and bulimia nervosa , Alzheimer's disease, cluster headaches and migraines, attention deficit hyperactivity disorder (ADHD), pain and Neuropathic pain, aphantasia, childhood-onset dysphagia, significant neurocognitive impairment, mild dementia CNS disorders, including cognitive impairment, sexual dysfunction, obesity, or a combination thereof 86. The method according to claims 83 to 85, wherein the disorder is a rheumatoid arthritis disorder.

88. 86. The method of claim 83, wherein the disease or disorder comprises a condition of the autonomic nervous system (ANS). How to do it.

89. The disease or disorder comprises a pulmonary disorder, including asthma and chronic obstructive pulmonary disorder (COPD). The method according to claims 83 to 85.

90. 83. The method of claim 82, wherein the disease or disorder comprises a cardiovascular disorder, including atherosclerosis. The method according to any one of claims 1 to 85.

91. The method according to claims 83 to 85 and 87, wherein the disease or disorder is an alcohol use disorder. How to post.

92. A tryptamine derivative or a compound according to any one of claims 1 to 81, and a poly A single-layer oral tablet composition comprising a mer.

93. 93. The monolayer oral administration tablet composition of claim 92, wherein the composition is adapted for maximum sustained release. thing.

94. The tablet composition comprises: (i) a water-insoluble, neutrally charged non-ionic matrix; (ii) one or more and (iii) a polymer carrying a negatively charged group of the tryptamine derivative or claim 93. The monolayer oral administration method according to claim 92, comprising a combination of a compound according to any one of claims 1 to 81. Administered tablet composition.

95. The nonionic matrix may be a cellulose-based polymer alone, or may be a starch or a wax. , neutral rubber, polymethacrylate, PVA, PVA / PVP blends, or mixtures thereof 95. The cellulosic polymer of claim 94, wherein the cellulosic polymer is reinforced by mixing with a compound. A single-layer oral tablet composition.

96. The cellulose-based polymer is hydroxypropyl methylcellulose (HPMC).

96. The monolayer oral administration tablet composition of claim 95,

97. The polymer carrying one or more negatively charged groups may be polyacrylic acid, polylactic acid, polyglycolic acid, or the like. Cholic acid, polymethacrylate carboxylate, cation exchange resin, clay, zeolite hyaluronic acid, anionic gums, salts thereof, or mixtures thereof.

5. The monolayer oral tablet composition according to claim 4.

98. the anionic rubber is a natural material, a semi-synthetic material, or a combination thereof; 98. The monolayer oral dosage tablet composition of claim 97.

99. The natural ingredients include alginic acid, pectin, xanthan gum, carrageenan, and locust. Strawberry gum, gum arabic, gum karaya, guar gum, gum tragacanth, or other 99. The monolayer oral administration tablet composition of claim 98, which is a combination thereof.

100. The semi-synthetic material is carboxymethyl-chitin, cellulose gum, or a combination thereof.

99. The monolayer orally administered tablet composition of claim 98, which is a combination.

101. A therapeutically effective amount of the tryptamine derivative or any of claims 1 to 81 for the treatment of pain.

93. A monolayer orally administered tablet composition according to claim 92, comprising a compound according to any one of claims 92 to 93.

102. A therapeutically effective amount of the tryptamine derivative or the compound according to claims 1 to 81 for the treatment of brain injury.

93. The monolayer orally administered tablet composition of claim 92, comprising a compound according to any one of claims 92 to 93.

103. A therapeutically effective amount of the tryptamine derivative or the compound according to claims 1 to 81 for the treatment of depression.

93. The monolayer orally administered tablet composition of claim 92, comprising a compound according to any one of claims 92 to 93.

104. Serotonin 5-HT ２ Therapeutic for use in treating a receptor-associated disease or disorder an effective amount of the tryptamine derivative or the compound according to any one of claims 1 to 81 93. The monolayer oral dosage tablet composition of claim 92, comprising:

105. The disease or disorder is selected from the group consisting of post-traumatic stress disorder (PTSD), major depressive disorder (MD), D), treatment-resistant depression (TRD), bipolar I disorder, bipolar II disorder, and cyclothymic disorder including bipolar and related disorders, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), Anxiety disorder, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine Substance use disorders, including use disorders and cocaine use disorders, anorexia nervosa, and bulimia nervosa , Alzheimer's disease, cluster headaches and migraines, attention deficit hyperactivity disorder (ADHD), pain and Neuropathic pain, aphantasia, childhood-onset dysphagia, significant neurocognitive impairment, mild dementia CNS disorders, including cognitive impairment, sexual dysfunction, obesity, or a combination thereof 105. The monolayer orally administered tablet composition of claim 104, wherein the disorder is

106. 105. The method of claim 104, wherein the disease or disorder comprises a condition of the autonomic nervous system (ANS). Layered orally administered tablet composition.

107. The method according to claims 104 to 105, wherein the disease or disorder is an alcohol use disorder. Layered orally administered tablet composition.

108. The disease or disorder comprises a pulmonary disorder, including asthma and chronic obstructive pulmonary disorder (COPD).

105. The monolayer oral administration tablet composition of claim 104.

109. 10. The method of claim 10, wherein the disease or disorder comprises a cardiovascular disorder, including atherosclerosis.

5. The monolayer oral tablet composition according to claim 4.

110. The composition contains the tryptamine derivative or achieves a combined concentration of the compound according to any one of claims 1 to 81 and during the release period 93. The monolayer oral administration tablet composition of claim 92, wherein the monolayer or oral administration tablet composition maintains a concentration of

111. 93. The monolayer oral administration tablet composition of claim 92, wherein the polymer comprises one or more negatively charged groups. Finished product.

112. A tryptamine derivative or a compound according to any one of claims 1 to 81, and a poly A tablet composition formulated for oral administration comprising a medicament for the treatment of rheumatoid arthritis.

113. 113. The tablet composition of claim 112, wherein the polymer comprises one or more negatively charged groups.

114. 113. The tablet composition of claim 112, wherein the polymer comprises one or more acid groups.

115. 113. The method of claim 112, wherein the polymer comprises a water-insoluble, neutrally charged, non-ionic matrix. Tablet composition.

116. The nonionic matrix may be a cellulose-based polymer alone, or may be a starch or a wax. , neutral rubber, polymethacrylate, PVA, PVA / PVP blends, or mixtures thereof 116. The cellulosic polymer of claim 115, wherein the cellulosic polymer is reinforced by mixing with a compound. Tablet composition.

117. The cellulose-based polymer is hydroxypropyl methylcellulose (HPMC).

117. The tablet composition of claim 116.

118. 1) the monolayer orally administered tablet composition of claim 92, and 2) its use in the treatment of pain. A kit for treating a subject, comprising instructions for:

119. 1) the monolayer orally administered tablet composition of claim 92; and 2) its use in the treatment of brain injury. A kit for treating a subject, comprising instructions for use.

120. 1) the monolayer oral administration tablet composition of claim 92; and 2) its use in the treatment of depression. A kit for treating a subject, comprising instructions for use.

121. 1) the monolayer oral administration tablet composition of claim 92, and 2) serotonin 5-HT ２ Receiving a therapeutic method for the subject, including instructions for use in treating a disease or disorder associated with the condition; Kit for.

122. 119. The kit of claim 118, wherein the polymer comprises one or more negatively charged groups.

123. 120. The kit of claim 119, wherein the polymer comprises one or more negatively charged groups.

124. 121. The kit of claim 120, wherein the polymer comprises one or more negatively charged groups.

125. 122. The kit of claim 121, wherein the polymer comprises one or more negatively charged groups.

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