Prodrugs of ketamine, compositions and uses thereof

Abstract

This invention relates to ( S)-or ( R)-K ketamine (including isotopically labeled ketamine) prodrugs, their components, and uses. S)-or ( Compounds having formula (Ia) or (Ib) of prodrugs of ketamine (including isotopically labeled ketamine) and pharmaceutical compositions comprising compounds provided herein are intended for the treatment or prevention of CNS diseases. More specifically, these diseases include depression and pain.

Description

Prodrug of ketamine, its composition and use The present invention relates to the field of medical technology, and more specifically to ( S)-or( R)-ketamine (including isotope-labeled ketamine) prodrugs and their compositions and uses. More specifically, the compounds disclosed herein can be used as NMDA ( N-methyl-D-aspartate (NMDA) receptor antagonists are used to treat, prevent, or alleviate neurological and psychiatric disorders or diseases of the central nervous system associated with NMDA receptors. The pharmaceutical compositions disclosed herein also have the function of preventing, treating, or alleviating diseases associated with NMDA receptors. More specifically, related diseases include depression and pain. Related applications This application claims priority to and the benefit of U.S. patent application Ser. No. 62 / 615,948, filed in the U.S. Patent and Trademark Office on Jan. 10, 2018, the entire contents of which are incorporated herein by reference. Antidepressants are central nervous system therapies used to treat conditions such as major depressive disorder (MDD), dysthymic disorder, and seasonal affective disorder. MDD, also known as clinical depression, is a condition that lasts two weeks or longer and interferes with a person's ability to perform daily tasks and enjoy activities that previously brought them pleasure. Glutamate is the primary excitatory neurotransmitter in the brain. Similar to conventional neurotransmitters, glutamate is released from nerve cells, binds to receptors, and is removed via reuptake transporters. The glutamate receptor system is highly complex and can be separated into various receptor subtypes based on their molecular and pharmacological properties. Most clinical studies across a variety of CNS indications have focused on drugs that modulate glutamate function via the NMDA receptor. Glutamate and its receptor subtypes play a fundamental role in synaptic plasticity and influence processes fundamental to human mood, cognition, and reward. Additional roles include neurodevelopmental and neurotrophic effects, as well as neurodegeneration. Ketamine is classified as an NMDA receptor antagonist, although its pharmacological profile is complex and it binds to many receptors. It was first approved by the US FDA as a general anesthetic 50 years ago. Chemically, ketamine is ( R)-and( S)-K-he racemic mixture. In 1998, ( S)-ketamine is approved in the EU for general anesthesia. Repeated administration of ketamine is a potential continuation strategy for antidepressant treatment in patients who show an initial response to ketamine infusions. In 10 patients with TRD who had not responded to an average of eight antidepressants in their lifetime, repeated intravenous administration of ketamine over two weeks (six infusions) resulted in a mean reduction of 85% in the Montgomery-Asberg Depression Rating Scale (MADRS) after the sixth infusion. Although intravenous ( iv) While infusion of ketamine is effective and advantageous compared to other medications for treatment-resistant depression, this dosing regimen requires patients to be treated in a clinic. Ketamine has been studied in humans to assess its oral bioavailability. It was found that due to extensive first-pass metabolism, ketamine exhibited only 17% oral bioavailability in humans, which has prevented the development of an oral regimen. Furthermore, ketamine's side effects may be related to its high Cmax after bolus dosing. To overcome the pharmacokinetic deficiencies of ketamine, a prodrug approach will be used to identify viable ketamine derivatives that can significantly improve the pharmacokinetic profile of ketamine via oral administration. Sustained-release formulations may be desirable to eliminate peaks and troughs in drug plasma concentrations to avoid potential side effects. The following is only an overview of some aspects of the present invention, but is not limited thereto. All references in this specification are incorporated herein by reference in their entirety. When the disclosure of this specification differs from the cited case, the disclosure of this specification shall prevail. The present invention provides compounds and pharmaceutical compositions that regulate antagonistic NMDA receptors, their preparation and corresponding pharmaceutical compositions. The compounds and / or pharmaceutical compositions of the present invention can potentially be used to manufacture drugs for preventing, treating or improving (ameliorate) certain disorders or diseases (including depression and pain) associated with NMDA receptors in patients. Specifically, in one aspect, the present invention relates to a compound having a structure of formula (Ia) or (Ib) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: Where R is -C(=O)R 1 、-C(=O)OR 2 、 -C(=O)O(CHR 3 )OC(=O)R 4 or -CD 3; and X is -CH 3 or -CD 3; where R 1 is an optionally substituted or unsubstituted aryl-OH, aryl-NH 2. Alkenyl-OH, Alkenyl-NH 2. Alkyl-NH 2. Alkyl-OH, carbocyclic group or heterocyclic group containing one or more N or O; and X is -CH 3 or -CD 3; where R 2 is an optionally substituted or unsubstituted alkyl, aryl, carbocyclic group or heterocyclic group containing one or more O; and X is -CH 3 or -CD 3; where R 4 are independently substituted or unsubstituted alkyl, aryl, nitrogen heteroaryl, carbocyclic group or heterocyclic group containing one or more O or N, and R 3 is H or substituted or unsubstituted alkyl; and X is -CH 3 or -CD 3. One object of the present invention is that the compound having the structure of formula (Ia) or (Ib) is ( S)-or( R)-ketamine prodrugs, wherein the "NR" moiety can be cleaved in vivo by chemical hydrolysis or metabolic processes by endogenous enzymes. Compounds of Formula (Ia) or (Ib) may have the following properties: i) significantly improved oral bioavailability compared to ketamine; and ii) suitable for sustained-release formulations suitable for QD or BID administration to meet patient compliance and convenience. In another aspect, provided herein is a compound having a structure of Formula (IIa) or (IIb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: ; where R 1is an optionally substituted or unsubstituted aryl-OH, aryl-NH 2. Alkenyl-OH, Alkenyl-NH 2. Alkyl-NH 2. Alkyl-OH, carbocyclic group or heterocyclic group containing one or more N or O; and X is -CH 3 or -CD 3. In one embodiment, R 1 Amino C 1-6 Alkyl, -R 1a NHCOR 1b 、-R 1a OCOR 1b 、-R 1a COOR 1b 、 , or C 3-6 Heterocyclic group, wherein R 1 As needed, C 1-6 Alkyl, -OH or pendant oxy (=O) substituted, wherein R 1a and R 1b Independent H, C 1-6 Alkyl or C 2-6 Alkenyl, and R 1c -OH, C 1-3 Hydroxyalkyl, -OCOR 1b or -CH 2OCOR 1b . In one embodiment, the heterocyclic group containing one or more N or O is 、 、 or . In another aspect, provided herein is a compound having a structure of formula (IIIa) or (IIIb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: where R 2 is an optionally substituted or unsubstituted alkyl, aryl, carbocyclic group or heterocyclic group containing one or more O; and X is -CH 3 or -CD 3. In one embodiment, R 2 C 1-6 Alkyl, C 1-6 Hydroxyalkyl, amino C 1-6 Alkyl, -R 2a S(O) n1 R 2b 、-R 2a COOR 2b 、C 3-6 Aryl or C 3-6 Heterocyclic group, wherein R 2 As needed, C 1-6 Alkyl, -OH, C 1-6 Hydroxyalkyl, 、 、 、 or -R 2a COOR 2b Replace, but C 1-6 Alkyl 、 、 or Replace; R 2a C 1-6 Alkyl, where R 2a As needed, C 1-6 Alkyl or -NH 2 substituted; R 2b H or C 1-6 Alkyl; and n 1 is 0, 1, 2. In another aspect, provided herein is a compound having the structure of Formula (IVa) or (IVb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: , where R 4 are independently substituted or unsubstituted alkyl, aryl, nitrogen heteroaryl, carbocyclic group or heterocyclic group containing one or more O or N, and R 3 is H or substituted or unsubstituted alkyl; and X is -CH 3 or -CD 3. In one embodiment, R 3 H or C 1-6 alkyl. In one embodiment, R 4 C 1-6 Alkyl, amino C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -R 4a NCOR 4b 、-R 4a OCOR 4b 、 -R 4a S(O) n2 R 4b 、C 1-6 Heterocyclic group, C 1-5 Azaaryl or , where R 4 As needed, C 1-6 Alkyl, -NH 2. Pendant oxygen group (=O), C 1-6 Hydroxyalkyl, ,or Replace, but C 1-6 Alkyl or substituted; wherein R 4a C 1-6 Alkyl, R 4b C 1-6 Alkyl or C 1-6 Haloalkyl; R 4c is benzyl, R 4d H, or R 4c and R 4d Together with the carbon atom to which they are attached, they form C 5-6 heterocyclic group; and n 2 is 0, 1, or 2. In one embodiment, C 1-6 Heterocyclic groups are 、 、 、 or . In one embodiment, C 1-5 Azaaryl is ,in Optionally, one or more methyl groups or -NH 2 or a combination thereof. In one embodiment, for or . In another aspect, provided herein is a compound having the structure of Formula (Va) or (Vb) or (Vc) or (Vd) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: . In another aspect, provided herein is a pharmaceutical composition comprising a compound of the present invention. In one embodiment, the pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient carrier, adjuvant, vehicle, or combination thereof. In one embodiment, the pharmaceutical composition further comprises one or more pharmaceutically effective amounts of adjunctive therapeutic agents, wherein the adjunctive therapeutic agents are used to treat neurological and psychiatric disorders or diseases of the central nervous system. In one embodiment, the neurological or psychiatric disorder or disease of the central nervous system is depression or pain. In one embodiment, the adjunctive therapeutic agent is selected from the group consisting of at least one member of lithium, pharmaceutical or herbal antidepressants, anticonvulsants, mood stabilizers, antipsychotics, and benzodiazepines. In another aspect, provided herein is the use of the compound or the pharmaceutical composition for the manufacture of a medicament for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient. In another aspect, provided herein is the use of the compound or the pharmaceutical composition for the manufacture of a medicament for antagonizing NMDA receptors. In another aspect, provided herein is the use of the compound or the pharmaceutical composition for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient. In another aspect, provided herein is a use of the compound or the pharmaceutical composition for antagonizing NMDA receptors. In another aspect, provided herein is a method for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient, comprising administering to a patient in need thereof a therapeutically effective amount of the compound or the pharmaceutical composition. In another aspect, provided herein is a method of antagonizing an NMDA receptor in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of the compound or the pharmaceutical composition. In another aspect, provided herein are methods for preparing, isolating, and purifying compounds represented by Formulae (Ia) to (Vd). The biological test results show that the compounds provided herein have good antagonistic effects on NMDA receptors and exhibit better pharmacokinetic properties and bioavailability. In certain embodiments of the compounds, pharmaceutical compositions, and methods of the present invention, the compound of Formula (Ia) to (Vd) is selected from the classes of compounds described or exemplified in the detailed description below, or a pharmaceutically acceptable salt of such a compound. In another preferred embodiment, the present invention relates to methods for preparing a plurality of pharmaceutical compositions, each comprising an effective amount of at least one compound of Formula (Ia)-(Vd) or a pharmaceutically acceptable salt of a compound of Formula (Ia)-(Vd). The pharmaceutical compositions according to the present invention may further comprise at least one pharmaceutically acceptable excipient, carrier, adjuvant, solvent, support, or a combination thereof. If formulated as a fixed dose, such combination products utilize a compound of the invention within the dosage ranges described herein (or as known to those skilled in the art) and another pharmaceutically active agent or therapeutic agent within those dosage ranges. When combination formulations are inappropriate, the compounds of the invention may also be administered sequentially with known antidepressants and analgesics. In any combination therapy, the present invention is not limited by the order of administration; the compounds of Formulas (Ia) to (Vd) may be administered before or after the known antidepressants and analgesics. Such techniques are within the skill of those skilled in the art and the attending physician. Yet another embodiment is a method of administering a compound of the present invention to a subject (eg, a human) in need thereof by administering to the subject a pharmaceutical formulation of the present invention. Yet another embodiment is a method of preparing a pharmaceutical formulation of the present invention by mixing at least one pharmaceutically acceptable compound of the present invention and, optionally, one or more pharmaceutically acceptable additives or excipients. To prepare pharmaceutical compositions from the compounds of the present invention, an inert pharmaceutically acceptable carrier can be a solid or liquid. Solid form formulations include powders, tablets, dispersible granules, capsules, beads, cachets, and suppositories. Powders and tablets can contain from about 5% to about 95% active ingredient. Suitable solid carriers are known in the art, such as magnesium carbonate, magnesium stearate, talc, sugar, or lactose. Tablets, powders, cachets, and capsules can be used as solid dosage forms suitable for oral administration. Examples of pharmaceutically acceptable carriers and methods for making various compositions can be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co., Easton, Pa. Liquid form preparations include solutions, suspensions, and emulsions. For example, there are water or water-propylene glycol solutions for parenteral injection or the addition of sweeteners and opacifiers for oral solutions, suspensions, and emulsions. Liquid form preparations may also include solutions for intranasal administration. Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutically acceptable carrier, such as an inert compressed gas, eg nitrogen. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration. Such liquid forms include solutions, suspensions, and emulsions. The compounds of the present invention may also be deliverable transdermally. Transdermal compositions may take the form of creams, lotions, aerosols and / or emulsions, and may be contained in a transdermal patch of the matrix or reservoir type, as conventionally used for this purpose in the art. The compounds of the present invention may also be delivered subcutaneously. Preferably delivery is oral or intravenous. Preferably, the pharmaceutical formulation is in unit dosage form. In this form, the formulation is divided into suitably sized unit doses containing appropriate quantities of the active ingredient, eg, an effective amount to achieve the desired purpose. The amount of active compound in a unit dose formulation can be varied or adjusted to the range of about 1 mg to about 1000 mg, preferably about 1 mg to about 500 mg, more preferably about 1 mg to about 300 mg, and even more preferably about 1 mg to about 200 mg, depending on the particular application. The actual dosage used may vary depending on the patient's requirements and the severity of the condition being treated. It is within the ability of those skilled in the art to determine the appropriate dosage regimen for a particular situation. For convenience, the total daily dose may be divided and administered in batches over the course of a day if necessary. The dosage and frequency of the compound of the present invention and / or its pharmaceutically acceptable salt will be adjusted based on the judgment of the attending clinician regarding factors such as the patient's age, condition, and size, as well as the severity of the symptoms being treated. The typical recommended daily dosage regimen for oral administration can be from about 1 mg / day to about 300 mg / day, preferably 10 mg / day to 200 mg / day, in one to two divided doses. Any embodiment disclosed herein may be combined with other embodiments, as long as they do not conflict with each other, and this applies even if the embodiments are described under different aspects of the present invention. In addition, any technical features in one embodiment may be applied to corresponding technical features in other embodiments, as long as they do not conflict with each other, and this applies even if the embodiments are described under different aspects of the present invention. The foregoing is merely an overview of certain aspects disclosed herein and is not intended to be limiting in nature. These and other aspects and implementations are described more fully below. Detailed description and specific implementation For the sake of brevity, the disclosures of publications (including patents and patent applications) cited in this specification are incorporated herein by reference in their entirety. Most chemical names are generated using IUPAC nomenclature. Some chemical names are generated using different nomenclatures or alternative or commercial names known in the art. If there is a conflict between a name and structure, the structure shall prevail. Definitions and General Terms Reference will now be made in detail to certain embodiments of the present invention, examples of which are described in the accompanying structures and formulas. The present invention is intended to encompass all substitutes, modifications, and equivalents that may be included within the scope of the present invention as defined by the scope of the claims. Those skilled in the art will recognize that many methods and materials similar to or equal to those described herein can be used to practice the present invention. The present invention is in no way limited to the methods and materials described herein. If one or more of the incorporated documents, patents, and similar materials (including but not limited to defined terms, term usage, described technology, etc.) are different from or contradictory to the present case, the present case shall prevail. It should also be understood that, for clarity, certain features of the present invention described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the present invention described in the context of a single embodiment may also be provided individually or in any suitable subcombination. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned are incorporated herein by reference in their entirety. As used herein, the following definitions apply unless otherwise indicated. For purposes of the present invention, chemical elements are identified according to the Periodic Table of the Elements, CAS version, and Handbook of Chemistry and Physics, 75th Ed. 1994. Additionally, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007, the entire contents of which are incorporated herein by reference. As used above and throughout this disclosure, unless otherwise indicated, the following terms should be understood to have the following meanings. In the absence of a definition, conventional definitions known to those of ordinary skill in the art will prevail. In the event that a definition provided herein conflicts or differs from a definition provided in any referenced disclosure, the definition provided herein will prevail. As used herein, the terms "including," "comprising," and "containing" are used in their open and non-limiting sense. As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. In order to provide a more concise description, some of the quantitative expressions given herein do not conform to the term "about". It should be understood that, regardless of whether the term "about" is explicitly used, each quantity given herein refers to the actual given value, and it also means that the approximate value of this given value can be reasonably inferred based on ordinary skills in the art, including the equivalents and approximate values ​​of this given value due to experimental and / or measurement conditions. Whenever the yield is given as a percentage, the yield refers to the mass of the entity for which the yield is given relative to the maximum amount of the same entity that can be obtained under specific stoichiometric conditions. Unless otherwise stated, the concentration given as a percentage refers to the mass ratio. The term "optionally" or "optionally" means that the subsequently described event or circumstance can but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. The terms "optionally substituted" and "unsubstituted or substituted" are used interchangeably herein to mean that the structure is unsubstituted or substituted with one or more substituents disclosed herein, wherein substitution occurs at any valence-permitted and reasonable position of the structure or group provided herein. In general, the term "substituted" refers to the replacement of one or more hydrogen radicals in a given structure or group with a radical of a specified substituent. Unless otherwise specified, a substituent may have a substituent at every substitutable and reasonable position of the group. When more than one position in a given structure can be substituted with more than one substituent selected from a specified group, the substituents may be the same or different at each position. The substituents disclosed herein include, but are not limited to, D, F, Cl, Br, I, -N 3. -CN, -NO 2. -OH, -SH, -NH 2. Alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, aminoalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, etc. Chemical definition As used herein, "alkyl" refers to a saturated straight or branched chain hydrocarbon group having 1 to 12 carbon atoms. Representative alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, butyl, isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and the like, and longer alkyl groups such as heptyl, octyl, and the like. At various places in this specification, substituents of the compounds disclosed herein are disclosed in groups or ranges. It is specifically intended that the invention include each and every individual subcombination of the members of such groups and ranges. For example, the term "C 1-6 "Alkyl" is specifically intended to disclose separately methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl and C 6 alkyl. The term "D" refers to a single deuterium atom. The term "alkenyl" refers to a straight or branched monovalent hydrocarbon group containing 2 to 12 carbon atoms and at least one carbon-carbon sp2 double bond, and includes Cis" and " trans" orientation, or, E" and " The alkenyl group may be optionally substituted with one or more substituents described herein. The term "alkynyl" refers to a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms and at least one carbon-carbon sp triple bond, wherein the alkynyl radical may be optionally substituted with one or more substituents described herein. The terms "halogen" or "halo" are used interchangeably herein and refer to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). The term "alkoxy" refers to an alkyl group, as defined above, attached to the parent molecular moiety via an oxygen atom. Unless otherwise indicated, an alkoxy group contains 1-12 carbon atoms. In one embodiment, an alkoxy group contains 1-6 carbon atoms. In other embodiments, an alkoxy group contains 1-4 carbon atoms. In yet another embodiment, an alkoxy group contains 1-3 carbon atoms. An alkoxy group may be optionally substituted with one or more substituents disclosed herein. As used herein, "alkoxyalkyl" refers to -(alkyl)-O-(alkyl), where each "alkyl" is independently an alkyl group as defined above. "Aryl" refers to a monocyclic, bicyclic, or tricyclic aromatic group in which all rings are aromatic. For bicyclic or tricyclic ring systems, the individual aromatic rings are fused to each other. Exemplary aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl. The term "haloalkyl" refers to an alkyl group substituted with one or more halogen atoms, wherein alkyl is as defined herein. Some non-limiting examples of these groups include, but are not limited to, -CF 3. -CF 2CF 3. -CH 2CF 2CHF 2, etc. In one embodiment, "haloalkyl" refers to a lower C 1-4 Haloalkyl, where "C 1-4 "Haloalkyl" includes fluorine-substituted C 1-4 Haloalkyl, chlorine-substituted C 1-4 Haloalkyl, bromine-substituted C 1-4 Haloalkyl, iodine-substituted C 1-4 Specifically, fluorine-substituted C 1-4 Haloalkyl groups include -CH 2F, -CHF 2. -CF 3. -CH 2Cl, -CHCl 2. -CCl 3. -CH 2Br, -CHBr 2. -CBr 3. -CH 2CH 2F, -CH 2CHF 2. -CH 2CF 3. -CF 2CH 2F, -CF 2CHF 2. -CF 2CF 3. -CHFCF 3. -CHFCHF 2. -CHFCH 2F, -CH 2CH 2CF 3. -CH 2CF 2CHF 2, etc. The haloalkyl group is optionally substituted with one or more substituents described herein. The term "aminoalkyl" refers to an alkyl group substituted with one or more amino groups, wherein alkyl is as defined herein and the amino groups are optionally substituted. The term "alkyl substituted with hydroxy" or "hydroxyalkyl" refers to an alkyl group substituted with one or more hydroxy groups, wherein alkyl is as defined herein. Some non-limiting examples of such groups include, but are not limited to, hydroxymethyl, hydroxyethyl, 1,2-dihydroxyethyl, and the like. As used herein, the term "deuterium" refers to the stable isotope of hydrogen having one proton and one neutron. The terms "carbocyclyl" and "carbocycle" are used interchangeably herein to refer to monovalent or multivalent rings having 3 to 12 carbon atoms in the form of monocyclic, bicyclic or tricyclic ring systems, which are saturated or contain one or more degrees of unsaturation, but in carbocyclyl groups there are no aromatic rings. The term "hydroxy" refers to an -OH group. The terms "heterocyclyl" and "heterocycle" are used interchangeably herein to refer to a monovalent or polyvalent monocyclic, bicyclic or tricyclic ring containing from 3 to 12 carbon atoms, wherein one or more atoms in each ring are independently replaced by a heteroatom, as defined herein, and the rings may be saturated or contain one or more degrees of unsaturation, but aromatic rings cannot be present. The term "cycloalkyl" refers to a monovalent or multivalent saturated ring having 3 to 12 ring carbon atoms in the form of a monocyclic, bicyclic or tricyclic ring system. One of ordinary skill in the art will recognize that the species of heteroaryl and cycloalkyl groups listed or exemplified above are not exhaustive, and that additional species may be selected within the scope of these defined terms. As described herein, the compounds disclosed herein may be optionally substituted with one or more substituents, as desired, or as exemplified within particular classes, subclasses, and species of the invention. As used herein, the term "substituted" refers to a specified group or moiety with one or more suitable substituents. As used herein, the term "unsubstituted" refers to a specified group without substituents. As used herein, the term "optionally substituted" refers to a specified group with either no substituents or a specified number of substituents. When the term "substituted" is used to describe a structural system, substitution is intended to occur at any valence-permitted position on the system. As used herein, the expression "one or more substituents" refers to the maximum number of substitutions that can occur at any valence-allowed position on the system. In one embodiment, one or more substituents refers to 1, 2, 3, 4, or 5 substituents. In another embodiment, one or more substituents refers to 1, 2, or 3 substituents. It is assumed that an atom shown herein with unsatisfied valences has a sufficient number of hydrogen atoms to satisfy the valences of the atom. When any variable (e.g., alkyl, alkylenyl, heteroaryl, R 1 、R 2 , or R a ) occurs in multiple places in any formula or description provided herein, its definition at each occurrence is independent of its definition at every other occurrence. As used herein, numerical ranges are intended to include consecutive integers. For example, a range expressed as "0 to 4" or "0-4" includes 0, 1, 2, 3, and 4, while a range expressed as "10-20%" includes 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, and 20%. Similarly, numerical ranges are also intended to include consecutive fractions. For example, a range expressed as "1-2%" includes 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, and 2.0%. When a multifunctional moiety is shown, the point of attachment to the core is represented by a line or hyphen. For example, aryloxy- refers to a moiety where the oxygen atom is the point of attachment to the core and the aryl group is attached to the oxygen atom. Additional Definitions As used herein, the term "subject" includes mammals and non-mammals. Examples of mammals include, but are not limited to, any member of the class mammalia: humans; non-human primates such as chimpanzees, and other apes and monkeys; farm animals such as cattle, horses, sheep, goats, and pigs; livestock such as rabbits, dogs, and cats; and laboratory animals, including rodents such as rats, mice, and guinea pigs. Examples of non-mammals include, but are not limited to, birds, fish, and the like. In one embodiment of the present invention, the mammal is a human. "Patient" includes humans and animals. The term "inhibitor" refers to a molecule, such as a chemical compound, drug, enzyme activator, or hormone, that blocks or otherwise interferes with a specific biological activity. The term "modulator" refers to a molecule, such as a compound of the invention, that increases, decreases or otherwise affects the activity of a given protein, receptor and / or ion channel. The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to provide the desired biological result. The result can be a reduction and / or alleviation of the signs, symptoms, or causes of a disease or medical condition, or any other desired change in a biological system. For example, an "effective amount" for therapeutic use is the amount of a compound or a composition comprising the compound required to provide a clinically relevant change in a disease state, symptom, or medical condition. In any individual case, an appropriate "effective" amount can be determined by one of ordinary skill in the art using routine experimentation. Thus, the expression "effective amount" generally refers to an amount of an active substance that provides the therapeutically desired effect. As used herein, the terms "treat" or "treatment" encompass both "preventative" and "curative" treatments. "Preventative" treatment is intended to mean delaying the development of a disease, symptoms of a disease or medical condition, inhibiting symptoms that may develop, or reducing the risk of a disease or symptom developing or recurring. "Curative" treatment includes reducing the severity of an existing disease, symptom, or condition or inhibiting its worsening. Thus, treatment includes ameliorating or preventing worsening of existing disease symptoms, preventing the appearance of additional symptoms, ameliorating or preventing potential metabolic causes of symptoms, inhibiting the disease or disease, e.g., stopping the development of the disease or disease, relieving the disease or disease, causing regression of the disease or disease, relieving a condition caused by the disease or disease, or stopping the symptoms of the disease or disease. As used herein, the terms "administration" and "administering" a compound should be understood to mean providing a compound of the present invention, a pharmaceutical composition comprising a compound of the present invention, or a prodrug of a compound of the present invention to a subject in need thereof. It should be recognized that one of ordinary skill in the non-limiting art can treat a patient currently suffering from a neurological or psychiatric disorder, or prophylactically treat a patient suffering from such a disorder by administering an effective amount of a compound of the present invention. As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product that results, directly or indirectly, from the combination of the specified ingredients in the specified amounts. Such terms, in relation to pharmaceutical compositions, are intended to encompass a product comprising one or more active ingredients and one or more inert ingredients that constitute a carrier, as well as any product that results, directly or indirectly, from the combination, complexation or aggregation of any two or more of such ingredients, or from some other type of reaction or interaction, such as that which causes the dissociation of one or more of such ingredients. Thus, the pharmaceutical compositions of the present invention encompass any composition made by mixing a compound of the present invention and a pharmaceutically acceptable carrier. Additional Chemical Description Any formula given herein is intended to represent compounds having the structure shown in the structural formula, as well as certain variants or forms. For example, any compound of any formula given herein may have asymmetric or chiral centers and therefore exist in different stereoisomeric forms. All stereoisomers of the general formula compound, including optical isomers, enantiomers and diastereomers, and mixtures thereof, are considered to fall within the scope of the formula. In addition, certain structures may exist in the form of geometric isomers (i.e., cis and trans isomers), tautomers, or atropisomers. All such isomeric forms and mixtures thereof are considered to be part of the present invention herein. Therefore, any formula given herein is intended to represent a racemate, one or more enantiomeric forms, one or more diastereomeric forms, one or more tautomers or atropisomers, and mixtures thereof. "Stereoisomers" refer to compounds that have identical chemical constitution but differ in the arrangement of the atoms or groups in space. Stereoisomers include enantiomers, diastereomers, configurational isomers (rotamers), geometric (cis / trans) isomers, atropisomers, and the like. "Chiral" refers to molecules that have the property of being non-superimposable on their mirror image partner, whereas the term "achiral" refers to molecules that are superimposable on their mirror image partner. "Enantiomers" refers to two stereoisomers of a compound that are non-superimposable mirror images of one another. "Diastereomers" refers to stereoisomers that have two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting points, boiling points, spectral properties, or biological activities. Mixtures of diastereomers can be separated under high-resolution analytical procedures (such as electrophoresis) and chromatography (such as HPLC). Stereochemical definitions and conventions used herein generally follow S. P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994. Many organic compounds exist in optically active forms, that is, they have the ability to rotate the plane of polarized light. When describing optically active compounds, the prefixes D and L, or R and S is used to indicate the absolute configuration of a molecule with respect to its chiral center. d and l or (+) and (-) are used to indicate the sign of the plane polarized light rotated by the compound, (-) or l indicates that the compound is left-handed. The compound of d is dextrorotatory. A specific stereoisomer can be called an enantiomer, and a mixture of such stereoisomers is called an enantiomeric mixture. A 50:50 mixture of enantiomers is called a racemic mixture or racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or procedure. Any asymmetric atom (e.g., carbon, etc.) of one or more compounds disclosed herein may be in a racemically enriched or enantiomerically enriched configuration. R)-、( S)-or( In certain embodiments, each asymmetric atom has an enantiomeric excess of at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%. R)-or( S)-configuration. Depending on the choice of starting materials and procedures, the compounds may exist in the form of one of the possible stereoisomers or in the form of mixtures thereof, such as racemates and diastereomeric mixtures, depending on the number of asymmetric carbon atoms. Optical activity ( R)-and( S)-isomers can be prepared using chiral synthetic components or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituents can be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis or trans configuration relative to the other substituent of the same cycloalkyl backbone. Any resulting mixture of stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers based on the physicochemical differences of the constituent components, for example, by chromatography and / or fractional crystallization. Any resulting racemate of the final product or intermediate can be resolved into its optical antipodes by methods known to those of ordinary skill in the art, for example, by separation of its diastereomeric salts. The racemic product can also be resolved by chiral chromatography, for example, high performance liquid chromatography (HPLC) using a chiral adsorbent. Preferred enantiomers can also be prepared by asymmetric synthesis. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Principles of Asymmetric Synthesis (2nd Ed. Robert E. Gawley, Jeffrey Aubé, Elsevier, Oxford, UK, 2012); Eliel, EL Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SH Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972); Chiral Separation Techniques: A Practical Approach (Subramanian, G. Ed., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2007). Non-enantiomer mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., a chiral auxiliary such as a chiral alcohol or Mosher's acyl chloride); or by forming a mixture of diastereomeric salts, separating the diastereomers, and converting (e.g., hydrolyzing or desalting) the individual diastereomers to the corresponding pure enantiomers. Enantiomers can also be separated using a chiral HPLC column. The compounds of the present invention may form pharmaceutically acceptable salts, which also fall within the scope of the present invention. "Pharmaceutically acceptable salts" refers to salts of the free acids or bases of the compounds of Formula A that are non-toxic, physiologically tolerable, compatible with the pharmaceutical composition in which they are formulated, and otherwise suitable for formulation and / or administration to a subject. Unless otherwise indicated, references to compounds herein should be understood to include pharmaceutically acceptable salts of the compounds. Salts of the compounds include acid salts formed with inorganic and / or organic acids, as well as basic salts formed with inorganic and / or organic bases. In addition, when a given compound contains a basic moiety (such as, but not limited to, pyridine or imidazole) and an acidic moiety (such as, but not limited to, a carboxylic acid), one of ordinary skill in the art will recognize that the compound may exist as a zwitterion ("inner salt"); such salts are included in the term "salt" as used herein. Salts of the compounds of the present invention can be prepared, for example, by reacting the compound with an amount (such as an equal amount) of a suitable acid or base in a medium, such as a medium in which the salt will precipitate or in an aqueous medium, followed by lyophilization. Exemplary salts include, but are not limited to, sulfates, citrates, acetates, oxalates, chlorides, bromides, iodides, nitrates, bisulfates, phosphates, acid phosphates, isonicotinates, lactates, salicylates, citrates, tartrates, oleates, tannates, pantothenates, bitartrates, ascorbates, succinates, maleates, gentisates, fumarates, gluconates, glucuronates, saccharates, formates, benzoates, glutamate, methanesulfonates ("mesylate"), ethanesulfonates, benzenesulfonates, p-toluenesulfonates, and pamoate (i.e., 1,1'-methylenebis(2-hydroxy-3-naphthoate)). Pharmaceutically acceptable salts may involve the inclusion of additional molecules such as acetate ions, succinate ions, or other counterions. Counterions can be any organic or inorganic moiety that stabilizes the charge on the parent compound. In addition, pharmaceutically acceptable salts may have more than one charged atom in their structure. Where multiple charged atoms are part of a pharmaceutically acceptable salt, there may be multiple counterions. Thus, a pharmaceutically acceptable salt may have one or more charged atoms and / or one or more counterions. Exemplary acid addition salts include acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate, naphthenate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonates (also known as tosylates), and the like. Exemplary basic salts include ammonium salts, alkali metal salts (such as sodium salts, lithium salts and potassium salts), alkaline earth metal salts (such as calcium salts and magnesium salts), salts formed with organic bases, for example, organic amines (such as dicyclohexylamine, tert-butylamine), salts formed with amino acids (such as arginine, lysine, etc.). Basic nitrogen-containing groups can be quaternized with groups such as lower alkyl halides (e.g., methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, butyl chloride, butyl bromide, and butyl iodide), dialkyl sulfates (e.g., dimethyl sulfate, diethyl sulfate, and dibutyl sulfate), long-chain halides (e.g., decyl chloride, decyl bromide, decyl iodide, lauryl chloride, lauryl bromide, lauryl iodide, stearyl chloride, stearyl bromide, stearyl iodide, lower alkyl halides), aralkyl halides (e.g., benzyl bromide and phenethyl bromide), and the like. Additionally, acids and bases generally considered suitable for forming pharmaceutically useful salts from pharmaceutical compounds are discussed, for example, in P. Stahl et al, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use.; (2002) Zurich: Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and The Orange Book (Food & Drug Administration, MD, available from FDA). The disclosures of these are incorporated herein by reference. In addition, any compound described herein is also intended to refer to any unsolvated form, or hydrates, solvates or isomorphs of such compound, and mixtures thereof, even if such forms are not explicitly listed. "Solvate" refers to a physical association of a compound of the invention with one or more solvent molecules. This physical association involves various degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, the solvate will be able to be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvate" encompasses solution phase and isolable solvates. Suitable solvates include solvates formed with pharmaceutically acceptable solvents such as water, ethanol, etc. In some embodiments, the solvent is water and the solvate is a hydrate. One or more compounds of the invention may be converted into solvates as desired. Methods for preparing solvates are generally known. Thus, for example, M. Caira et al., J. Pharmaceutical Sci., 93(3), 601-611 (2004) describe the preparation of solvates of the antifungal agent fluconazole in ethyl acetate and from water. Similar preparations of solvates, hemisolvates, hydrates, etc. are described in EC van Tonder et al., J. Pharmaceutical Sci., 93(3), 601-611 (2004). et al, AAPS PharmSciTech., 5(1), article 12 (2004); and AL Bingham et al, Chem. Commun., 603-604 (2001). A typical, non-limiting procedure involves dissolving the compound of the invention in a suitable amount of solvent (organic solvent or water or a mixture thereof) at a temperature above ambient temperature, cooling the solution at a rate sufficient to form crystals, and then isolating the crystals by standard methods. Analytical techniques, such as infrared spectroscopy, indicate the presence of solvent (or water) in the crystals as a solvate (or hydrate). The present invention also relates to pharmaceutically active metabolites of the compounds of formula (A), and the use of these metabolites in the methods of the present invention. "Pharmaceutically active metabolites" refer to pharmaceutically active products that are metabolized in vivo by the compounds of formula (A) or their salts. The active metabolites of the compounds can be determined using conventional techniques known or available in the art. See, for example, Bertolini et al., J. Med. Chem. 1997, 40, 2011-2016; Shan et al., J. Pharm. Sci. 1997, 86 (7), 765-767; Bagshawe, Drug Dev. Res. 1995, 34, 220-230; Bodor, Adv. Drug Res. 1984, 13, 255-331; Bundgaard, Design of Prodrugs (Elsevier Press, 1985); and Larsen, Design and Application of Prodrugs, Drug Design and Development (Krogsgaard-Larsen et al., eds., Harwood Academic Publishers, 1991). Any formula given herein is also intended to represent unlabeled forms of the compounds as well as isotopically labeled forms of the compounds. Isotopically labeled compounds have structures represented by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, for example 2 H. 3 H. 11 C. 13 C. 14 C. 15 N. 18 O. 17 O. 31 P. 32 P. 35 S. 18 F. 36 Cl, and 125 I. Such isotope-labeled compounds can be used for metabolic studies (e.g. 14 C), reaction kinetics studies (e.g. 2 H or 3 H), detection or imaging techniques [such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) including drug or substrate tissue distribution tests, or radiotherapy for patients. In particular, 18 F or 11 Compounds labeled with C may be particularly useful for PET or SPECT studies. In addition, compounds labeled with heavier isotopes such as deuterium (i.e. 2 H) substitution may provide certain therapeutic advantages due to greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Isotopically labeled compounds of the present invention can generally be prepared by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent and carrying out the methods disclosed in the following schemes or examples and formulations. The use of the terms "salts," "solvates," "isomorphs," and the like with respect to the compounds described herein is intended to apply equally to the salts, solvates, and isomorphs of the enantiomers, stereoisomers, rotamers, tautomers, atropisomers, and racemates of the compounds of the invention. Description of the Compounds of the Invention This article provides the S)-or( R)-ketamine (including isotope-labeled ketamine) prodrugs and their compositions and uses. More specifically, as ( S)-or( The compounds of formula (Ia) to (Vd) disclosed herein, which are prodrugs of R)-ketamine (including isotope-labeled ketamine), can be used as NMDA receptor antagonists for treating, preventing, or alleviating neurological and psychiatric disorders or diseases of the central nervous system associated with NMDA receptors. The pharmaceutical compositions disclosed herein also have the function of preventing, treating, or alleviating diseases associated with NMDA receptors. In one embodiment of the present invention, there is provided a compound having a structure of formula (Ia) or (Ib) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: Where R is -C(=O)R 1 、-C(=O)OR 2 、 -C(=O)O(CHR 3 )OC(=O)R 4 or -CD 3; and X is -CH 3 or -CD 3. Among them R 1 is an optionally substituted or unsubstituted aryl-OH, aryl-NH 2. Alkenyl-OH, Alkenyl-NH 2. Alkyl-NH 2. Alkyl-OH, carbocyclic group or heterocyclic group containing one or more N or O; and X is -CH 3 or -CD 3; where R 2 is an optionally substituted or unsubstituted alkyl, aryl, carbocyclic group or heterocyclic group containing one or more O; and X is -CH 3 or -CD 3; where R 4 are independently substituted or unsubstituted alkyl, aryl, nitrogen heteroaryl, carbocyclic group or heterocyclic group containing one or more O or N, and R 3 is H or substituted or unsubstituted alkyl; and X is -CH 3 or -CD 3. In another aspect, provided herein is a compound having a structure of Formula (IIa) or (IIb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: ; where R 1 is an optionally substituted or unsubstituted aryl-OH, aryl-NH 2. Alkenyl-OH, Alkenyl-NH 2. Alkyl-NH 2. Alkyl-OH, carbocyclic group or heterocyclic group containing one or more N or O; and X is -CH 3 or -CD 3. In one embodiment, R 1 Amino C 1-6 Alkyl, -R 1a NHCOR 1b 、-R 1a OCOR 1b 、-R 1a COOR 1b 、 , or C 3-6 Heterocyclic group, wherein R 1 As needed, C 1-6 Alkyl, -OH or pendant oxy (=O) substituted, wherein R 1a and R 1b Independent H, C 1-6 Alkyl or C 2-6 Alkenyl, and R 1c -OH, C 1-3 Hydroxyalkyl, -OCOR 1b or -CH 2OCOR 1b . In one embodiment, the heterocyclic group containing one or more N or O is 、 、 or . In another aspect, provided herein is a compound selected from the group consisting of, Where X is -CH 3 or -CD 3. In another aspect, provided herein is a compound having a structure of formula (IIIa) or (IIIb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: where R 2 is an optionally substituted or unsubstituted alkyl, aryl, carbocyclic group or heterocyclic group containing one or more O; and X is -CH 3 or -CD 3. In one embodiment, R 2 C 1-6 Alkyl, C 1-6 Hydroxyalkyl, amino C 1-6 Alkyl, -R 2a S(O) n1 R 2b 、-R 2a COOR 2b 、C 3-6 Aryl or C 3-6 Heterocyclic group, wherein R 2 As needed, C 1-6 Alkyl, -OH, C 1-6 Hydroxyalkyl, 、 、 、 or -R 2a COOR 2b Replace, but C 1-6 Alkyl 、 、 or Replace; R 2a C 1-6 Alkyl, where R 2a As needed, C 1-6 Alkyl or -NH 2 substituted; R 2b H or C 1-6 Alkyl; and n 1 is 0, 1, 2. In another aspect, provided herein is a compound selected from the group consisting of, Where X is -CH 3 or -CD 3. In another aspect, provided herein is a compound having the structure of Formula (IVa) or (IVb) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: , where R 4 are independently substituted or unsubstituted alkyl, aryl, nitrogen heteroaryl, carbocyclic group or heterocyclic group containing one or more O or N, and R 3 is H or substituted or unsubstituted alkyl; and X is -CH 3 or -CD 3. In one embodiment, R 3 H or C 1-6 alkyl. In one embodiment, R 4 C 1-6 Alkyl, amino C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -R 4a NCOR 4b 、-R 4a OCOR 4b 、 -R 4a S(O) n2 R 4b 、C 1-6 Heterocyclic group, C 1-5 Azaaryl or , where R 4 As needed, C 1-6 Alkyl, -NH 2. Pendant oxygen group (=O), C 1-6 Hydroxyalkyl, ,or Replace, but C 1-6 Alkyl or substituted; wherein R 4a C 1-6 Alkyl, R 4b C 1-6 Alkyl or C 1-6 Haloalkyl; R 4c is benzyl, R 4d H, or R 4c and R 4d Together with the carbon atom to which they are attached, they form C 5-6 heterocyclic group; and n 2 is 0, 1, or 2. In one embodiment, C 1-6 Heterocyclic groups are 、 、 、 or . In one embodiment, C 1-5 Azaaryl is ,in Optionally, one or more methyl groups or -NH 2 or a combination thereof. In one embodiment, for or . In another aspect, provided herein is a compound selected from the group consisting of, Where X is -CH 3 or -CD 3. In another aspect, provided herein is a compound having the structure of Formula (Va) or (Vb) or (Vc) or (Vd) or a stereoisomer thereof, N-oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of: . Unless otherwise stated, all suitable isotopic variations, stereoisomers, tautomers, solvates, metabolites, salts, and pharmaceutically acceptable prodrugs of the compounds disclosed herein are within the scope of the invention. The compounds shown in formulas (Ia) to (Vd) above may exist in different tautomeric forms, and all such tautomers are encompassed within the scope of the present invention. This paper discloses the compound N-oxides also fall within the scope of the present invention. N-oxides can be prepared by oxidation of the corresponding nitrogen base using a conventional oxidizing agent such as hydrogen peroxide in the presence of an acid such as acetic acid at elevated temperature, or by reaction with a peracid such as peracetic acid in a suitable solvent such as DCM, ethyl acetate or methyl acetate, or with 3-chloroperoxybenzoic acid in chloroform or DCM. In addition, when the compounds disclosed herein form hydrates or solvates, these also fall within the scope of the present invention. Similarly, pharmaceutically acceptable salts and solvates of the compounds disclosed herein also fall within the scope of the present invention. The compounds of formula (Ia) to (Vd) may exist in the form of salts. In some embodiments, the salt is a pharmaceutically acceptable salt. The pharmaceutically acceptable salts of the present invention can be synthesized from basic or acidic parts by conventional chemical methods. Generally, these salts can be prepared by reacting the free acid forms of these compounds with a stoichiometric amount of a suitable base (such as sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, sodium carbonate, calcium carbonate, magnesium carbonate, potassium carbonate, sodium bicarbonate, calcium bicarbonate, magnesium bicarbonate, potassium bicarbonate, etc.), or by reacting the free base forms of these compounds with a stoichiometric amount of a suitable acid. These reactions are typically carried out in water or an organic solvent, or in a mixture of the two. Generally, where feasible, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile are used. A list of additional suitable salts can be found, for example, in " Remington's Pharmaceutical Sciences”, 20th ed., Mack Publishing Company, Easton, Pa., (1985); and in “ Handbook of Pharmaceutical Salts: Properties, Selection, and Use” by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). The compounds of the present invention are basic and therefore can generally be formed into pharmaceutically acceptable acid addition salts by elaboration of a suitable acid. Suitable acids include pharmaceutically acceptable inorganic and organic acids. Representative pharmaceutically acceptable acid addition salts include hydrochlorides, hydrobromides, nitrates, methylnitrates, sulfates, bisulfates, sulfamates, phosphates, acetates, glycolates, phenylacetates, propionates, butyrates, isobutyrates, valerates, maleates, hydroxymaleates, acrylates, fumarates, malates, tartrates, citrates, salicylates, para-aminosalicylates, glycolates, lactates, heptanoates, phthalates, oxalates, succinates, benzoates. salt, acetyloxybenzoate, chlorobenzoate, methyl benzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, mandelate, tannate, formate, stearate, ascorbate, palmitate, oleate, pyruvate, pamoate, malonate, laurate, glutarate, glutamate, lauryl sulfate (estolate), methanesulfonate, ethylsulfate, 2-hydroxyesilate, benzenesulfonate, p-aminobenzenesulfonate, p-toluenesulfonate and naphthalene-2-sulfonate, etc. Any formula given herein is also intended to represent isotopically unenriched forms of the compound as well as isotopically enriched forms. An isotopically enriched compound has a structure represented by the general formula of the present invention, but with the exception of the fact that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as 2 H. 3 H. 11 C. 13 C. 14 C. 15 N. 17 O. 18 O. 18 F. 31 P. 32 P. 35 S. 36 Cl and 125 I. In another aspect, the compounds of the invention include isotopically enriched compounds as defined herein, for example, wherein a radioactive isotope is present, such as 3 H. 14 C and 18 F, or where non-radioactive isotopes such as 2 H and 13 C. Such isotopically enriched compounds can be used for metabolic studies (e.g. 14 C), reaction kinetics studies (e.g. 2 H or 3 H), detection or imaging techniques [such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) including drug or substrate tissue distribution studies, or radiation therapy for patients. 18 F-enriched compounds are particularly useful in PET or SPECT studies. Isotopically enriched compounds of formula (I) can generally be prepared by carrying out the methods disclosed in the following schemes or examples and preparations by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. In another aspect, provided herein is a pharmaceutical composition comprising a compound of the present invention. In one embodiment, the pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient carrier, adjuvant, vehicle or combination thereof. In one embodiment, the pharmaceutical composition further comprises one or more pharmaceutically effective amounts of adjunctive therapeutic agents, wherein the adjunctive therapeutic agents are used to treat neurological and psychiatric disorders or diseases of the central nervous system. In one embodiment, the neurological or psychiatric disorder or disease of the central nervous system is depression or pain. In one embodiment, the adjunctive therapeutic agent is selected from the group consisting of at least one member of lithium, pharmaceutical or herbal antidepressants, anticonvulsants, mood stabilizers, antipsychotics, and benzodiazepines. In another aspect, provided herein is the use of the compound or the pharmaceutical composition for the manufacture of a medicament for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient. In another aspect, provided herein is a use of the compound or the pharmaceutical composition for the manufacture of a medicament for antagonizing NMDA receptors. In another aspect, provided herein is a use of the compound or pharmaceutical composition for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient. In another aspect, provided herein is a use of the compound or the pharmaceutical composition to antagonize NMDA receptors. In another aspect, provided herein is a method for preventing, controlling, treating or alleviating neurological and psychiatric disorders or diseases of the central nervous system of a patient, comprising administering to a patient in need thereof a therapeutically effective amount of the compound or the pharmaceutical composition. In another aspect, provided herein is a method of antagonizing an NMDA receptor in a patient, comprising administering to a patient in need thereof a therapeutically effective amount of the compound or the pharmaceutical composition. In another aspect, the present invention relates to methods for preparing compounds of formula (Ia) to (Vd) and pharmaceutically acceptable salts thereof. Compositions, formulations and administration of the compounds of the present invention In one aspect, provided herein is a pharmaceutical composition comprising a compound of Formula (Ia)-(Vd) or a stereoisomer, tautomer, N-oxide, solvate, metabolite, pharmaceutically acceptable salt, or prodrug thereof. Optionally, the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier, adjuvant, or excipient, and optionally other therapeutic and / or prophylactic ingredients. Suitable carriers, adjuvants and excipients are well known to those skilled in the art and are described in detail in, for example, Ansel h. C. et al., Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems (2004) Lippincott, Williams & Wilkins, Philadelphia; Gennaro AR et al., Remington: The Science and Practice of Pharmacy (2000) Lippincott, Williams & Wilkins, Philadelphia; and Rowe RC, Handbook of Pharmaceutical Excipients (2005) Pharmaceutical Press, Chicago. As used herein, a "pharmaceutically acceptable excipient" refers to a pharmaceutically acceptable material, composition, or vehicle that imparts form or consistency to a pharmaceutical composition. Each excipient must be compatible with the other components of the pharmaceutical composition when mixed, thereby avoiding interactions that would significantly reduce the efficacy of the compounds of the invention when administered to a patient and that would result in a pharmaceutically unacceptable composition. Furthermore, each excipient must, of course, be of sufficiently high purity to be pharmaceutically acceptable. Suitable pharmaceutically acceptable excipients will vary depending on the specific dosage form selected. In addition, suitable pharmaceutically acceptable excipients can be selected so that they can serve a specific function in the composition. For example, certain pharmaceutically acceptable excipients can be selected because they promote the production of a uniform dosage form. Certain pharmaceutically acceptable excipients can be selected because they promote the production of a stable dosage form. Certain pharmaceutically acceptable excipients can be selected because they promote the carrying or transport of the compound of the present invention from one organ or part of the body to another organ or part of the body once administered to the patient. Certain pharmaceutically acceptable excipients can be selected because they enhance the patient's compliance. Suitable pharmaceutically acceptable excipients include the following types of excipients: diluents, fillers, binders, disintegrants, lubricants, glidants, granulating agents, coating agents, wetting agents, solvents, cosolvents, suspending agents, emulsifiers, sweeteners, flavorings, taste masking agents, coloring agents, anti-caking agents, humectants, chelating agents, plasticizers, viscosity increasing agents, antioxidants, preservatives, stabilizers, surfactants and buffers. Those skilled in the art will appreciate that certain pharmaceutically acceptable excipients can serve more than one role and can function as alternatives, depending on how much excipient is present in the formulation and which other components are present in the formulation. The skilled artisan has the knowledge and skill in the art that enables them to select an appropriate amount of a suitable pharmaceutically acceptable excipient for use in the present invention. In addition, there are many resources available to those of ordinary skill in the art that describe pharmaceutically acceptable excipients, and such resources can be used to select a suitable pharmaceutically acceptable excipient. Examples include Remington's Pharmaceutical Sciences (Mack Publishing Company), The Handbook of Pharmaceutical Additives (Gower Publishing Limited), and The Handbook of Pharmaceutical Excipients (the American Pharmaceutical Association and the Pharmaceutical Press). Various carriers for formulating pharmaceutically acceptable compositions and known techniques for preparing the same are disclosed in Remington: The Science and Practice of Pharmacy, 21st edition, 2005, ed. DB Troy, Lippincott Williams & Wilkins, Philadelphia, and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and JC Boylan, 1988-1999, Marcel Dekker, New York (the contents of which are incorporated herein by reference). Unless any conventional carrier medium is incompatible with the compounds of the invention, such as by producing any undesirable biological effect or interacting in a deleterious manner with any other component of the pharmaceutically acceptable composition, its use is intended to fall within the scope of the present invention. The compounds of the invention will typically be formulated into a dosage form suitable for administration to a patient by the intended route of administration. For example, dosage forms include those suitable for (1) oral administration, such as tablets, capsules, caplets, pills, troches, powders, syrups, elixirs, suspensions, solutions, emulsions, sachets, and cachets; (2) parenteral administration, such as sterile solutions, suspensions, and powders for reconstitution; (3) transdermal administration, such as transdermal patches; (4) rectal administration, such as suppositories; (5) inhalation, such as aerosols, solutions, and dry powders; and (6) topical administration, such as creams, ointments, lotions, solutions, pastes, sprays, foams, and gels. It should also be understood that certain compounds of the present invention may be present in therapeutically useful free form or, where appropriate, in the form of pharmaceutically acceptable derivatives or prodrugs thereof. According to the present invention, pharmaceutically acceptable derivatives or prodrugs include, but are not limited to, pharmaceutically acceptable prodrugs, salts, esters, salts of such esters, or any other adducts or derivatives that, when administered to a patient in need thereof, are capable of providing, directly or indirectly, a compound otherwise described herein or a metabolite or residue thereof. In one embodiment, the compounds disclosed herein can be prepared as oral dosage forms. In one embodiment, the compounds disclosed herein can be prepared as inhaled dosage forms. In one embodiment, the compounds disclosed herein can be prepared as nasal dosage forms. In one embodiment, the compounds disclosed herein can be prepared as transdermal dosage forms. In one embodiment, the compounds disclosed herein can be prepared as topical dosage forms. The pharmaceutical compositions provided herein can be provided in the form of compressed tablets, tablet grinders, chewable lozenges, fast-dissolving tablets, multiple compressed tablets, or enteric-coated tablets, sugar-coated, or film-coated tablets. Enteric-coated tablets are compressed tablets coated with a substance that resists the effects of gastric acid but dissolves or disintegrates in the intestines, thereby protecting the active ingredients from the acidic environment of the stomach. Enteric coatings include, but are not limited to, fatty acids, fats, phenyl salicylate, waxes, shellac, aminated shellac, and cellulose acetate phthalate. Sugar-coated tablets are compressed tablets surrounded by a sugar coating that can be helpful in masking unpleasant tastes or odors and protecting the tablet from oxidation. Film-coated tablets are compressed tablets covered with a thin layer or film of a water-soluble material. Film coatings include, but are not limited to, hydroxyethylcellulose, sodium carboxymethylcellulose, polyethylene glycol 4000, and cellulose acetate phthalate. Film coatings have the same general properties as sugar coatings. Multiple compressed tablets are compressed tablets made by more than one compression cycle, include multilayer tablets, and compression-coated or dry-coated tablets. Tablet dosage forms can be prepared from the active ingredient in powder, crystalline or granular form alone or in combination with one or more carriers or excipients described herein (including binders, disintegrants, controlled release polymers, lubricants, diluents and / or coloring agents). Flavorings and sweeteners are particularly useful in forming chewable tablets and lozenges. The pharmaceutical compositions provided herein can be provided in the form of soft or hard capsules, which can be made from gelatin, methylcellulose, starch, or calcium alginate. Hard gelatin capsules, also known as dry-fill capsules (DFCs), consist of two parts, one of which slides over the other, thereby completely encapsulating the active ingredient. Soft elastic capsules (SECs) are soft, spherical shells, such as gelatin shells, that are plasticized by the addition of glycerol, sorbitol, or similar polyols. The soft gelatin shells may contain a preservative to prevent microbial growth. Suitable preservatives are those described herein, including methyl and propyl parabens, as well as sorbic acid. Liquid, semisolid, and solid dosage forms provided herein can be encapsulated in capsules. Suitable liquid and semisolid dosage forms include solutions and suspensions in propylene carbonate, vegetable oils, or triglycerides. Capsules containing such solutions can be prepared as described in U.S. Patent Nos. 4,328,245; 4,409,239; and 4,410,545. The capsules may also be coated as is known to those skilled in the art to modify or maintain dissolution of the active ingredient. The pharmaceutical compositions provided herein can be provided in liquid and semisolid dosage forms, including emulsions, solutions, suspensions, elixirs, and syrups. Emulsions are two-phase systems in which one liquid is dispersed in the form of small globules throughout another liquid, which can be oil-in-water or water-in-oil. Emulsions can include a pharmaceutically acceptable non-aqueous liquid or solvent, an emulsifier, and a preservative. Suspensions can include a pharmaceutically acceptable suspending agent and a preservative. Aqueous alcoholic solutions can include pharmaceutically acceptable acetals, such as di(lower alkyl) acetals of lower alkyl aldehydes, for example, acetaldehyde diethyl acetal; and water-miscible solvents having one or more hydroxyl groups, such as propylene glycol and ethanol. Elixirs are clear and sweet hydroalcoholic solutions. Syrups are concentrated aqueous solutions of sugars (e.g., sucrose) and may also contain preservatives. For liquid dosage forms, for example, a solution in polyethylene glycol can be diluted with a sufficient amount of a pharmaceutically acceptable liquid carrier (e.g., water) to facilitate measurement for administration. Provided herein is a pharmaceutical composition that can be prepared into a dosage form suitable for administration to a patient by inhalation, such as a dry powder, aerosol, suspension, or solution composition. In one embodiment, the present invention is directed to a dosage form suitable for administration to a patient by inhalation as a dry powder. In one embodiment, the present invention is directed to a dosage form suitable for administration to a patient by inhalation as a dry powder. Dry powder compositions for delivery to the lungs by inhalation typically comprise a compound disclosed herein or a pharmaceutically acceptable salt thereof as a finely divided powder together with one or more pharmaceutically acceptable excipients as a finely divided powder. Pharmaceutically acceptable excipients particularly suitable for dry powders are known to those of ordinary skill in the art and include lactose, starch, mannitol, and monosaccharides, disaccharides, and polysaccharides. Finely divided powders can be prepared, for example, by micronization and grinding. Typically, size-reduced (e.g., micronized) compounds can be prepared with a D of about 1 to 10 microns. 50 values ​​(e.g. using laser diffraction measurements). Pharmaceutical compositions suitable for transdermal administration may be presented as discrete patches designed to maintain close contact with the patient's epidermis for an extended period of time. For example, the active ingredient may be delivered from the patch by iontophoresis, as generally described in Pharmaceutical Research, 3(6), 318 (1986). The pharmaceutical composition that is applicable to topical administration can be formulated into ointment, cream, suspension, lotion, powder, solution, paste, gel, spray, aerosol or oil. Ointment, cream and gel can be for example deployed with aqueous or oily base, adding suitable thickener and / or gelling agent and / or solvent simultaneously. Therefore, such substrate can comprise for example water and / or oil such as liquid paraffin or vegetable oil such as peanut oil or castor oil or solvent such as polyethylene glycol. The thickener and gelling agent that can be used according to the property of substrate comprise soft paraffin, aluminum stearate, cetearyl alcohol, polyethylene glycol, lanolin, beeswax, carboxypolymethylene and cellulose derivative and / or glyceryl monostearate and / or nonionic emulsifier. The compounds disclosed herein can also be coupled with soluble polymers as targetable drug carriers. These polymers may include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamidophenol, polyhydroxyethylaspartamidophenol, or polyethylene oxide polylysine substituted with palmitoyl groups. Furthermore, the compounds can be coupled with a class of biodegradable polymers suitable for achieving controlled drug release, such as cross-linked or amphiphilic block copolymers of polylactic acid, poly-ε-caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydroxypyrans, polycyanoacrylates, and hydrogels. The pharmaceutical compositions provided herein can be administered parenterally by injection, infusion, or implantation for local or systemic administration. As used herein, parenteral administration includes intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, ​​intrasternal, intracranial, intramuscular, intrasynovial, and subcutaneous administration. The pharmaceutical compositions provided herein can be formulated into any dosage form suitable for parenteral administration, including solutions, suspensions, emulsions, microcapsules, liposomes, microspheres, nanosystems, and solid forms suitable for solution or suspension in a liquid prior to injection. These dosage forms can be prepared according to conventional methods known to those skilled in the art of pharmaceuticals (see Remington: The Science and Practice of Pharmacy, supra). Pharmaceutical compositions intended for parenteral administration may include one or more pharmaceutically acceptable carriers and excipients, including but not limited to aqueous vehicles, water-miscible vehicles, non-aqueous vehicles, antimicrobial agents or preservatives against microbial growth, stabilizers, solubility enhancers, isotonicity agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, wetting or emulsifying agents, complexing, clamping or chelating agents, cryoprotectants, lyoprotectants, thickening agents, pH adjusters and inert gases. The pharmaceutical compositions provided herein can be formulated as immediate or modified release dosage forms, including delayed-, sustained-, pulsed-, controlled-, targeted-, and programmed-release forms. The pharmaceutical compositions provided herein can be formulated for single or multiple dose administration. Single dose formulations are packaged in ampoules, vials, or syringes. Multiple dose parenteral formulations must contain an antimicrobial agent at a bacteriostatic or fungistatic concentration. As known and practiced in the art, all parenteral formulations must be sterile. The pharmaceutical compositions provided herein can be formulated with other active ingredients that do not impair the desired therapeutic effect, or with substances that supplement the desired effect. In one embodiment, the treatment methods disclosed herein comprise administering a safe and effective amount of a compound of the present invention or a pharmaceutical composition containing a compound of the present invention to a patient in need of such treatment. The various embodiments disclosed herein comprise treating the aforementioned conditions or diseases by administering a safe and effective amount of a compound of the present invention or a pharmaceutical composition containing a compound of the present invention to a patient in need of such treatment. In one embodiment, the compounds of the present invention or its pharmaceutical composition can be administered by any suitable route of administration, including both systemic administration and topical administration. Systemic administration includes oral administration, parenteral administration, transdermal administration, and rectal administration. Parenteral administration refers to administration routes other than enteral or transdermal, and is typically by injection or infusion. Parenteral administration includes intravenous, intramuscular, and subcutaneous injection or infusion. Topical administration includes application to the skin and intraocular, ear, vaginal, inhalation, and intranasal administration. In one embodiment, the compounds of the present invention or its pharmaceutical composition can be administered orally. In one embodiment, the compounds of the present invention or its pharmaceutical composition can be administered by inhalation. In another embodiment, the compounds of the present invention or its pharmaceutical composition can be administered intranasally. In one embodiment, the compounds of the present invention or its pharmaceutical composition can be administered once or according to a dosing regimen in which multiple doses are administered at varying intervals over a given period of time. For example, the dose can be administered once, twice, three times, or four times a day. In one embodiment, the dose is administered once a day. In another embodiment, the dose is administered twice a day. The dose can be administered until the desired therapeutic effect is achieved or the desired therapeutic effect is maintained indefinitely. The dosing regimen suitable for the compounds of the present invention or its pharmaceutical composition depends on the pharmacokinetic properties of the compound, such as absorption, distribution, and half-life, which can be determined by those with ordinary knowledge in the art. In addition, the appropriate dosing regimen of the compounds of the present invention or its pharmaceutical composition (including the duration of administering these regimens) will depend on the disease being treated, the severity of the disease being treated, the age and physical condition of the patient being treated, the medical history of the patient to be treated, the nature of the concurrent therapy, the desired therapeutic effect, and similar factors within the scope of the knowledge and professional opinions of those with ordinary knowledge in the art. Those skilled in the art will further appreciate that the appropriate dosing regimen may need to be adjusted to take into account an individual patient's response to the dosing regimen or as the individual patient's needs change over time. The compounds of the present invention may be administered simultaneously with, before, or after one or more other therapeutic agents. The compounds of the present invention may be administered separately, by the same or different routes of administration as other drugs in the same pharmaceutical composition, or administered together. The compounds provided herein can be used in combination with sedatives, hypnotics, anxiolytics, antipsychotics, anxiolytics, cyclopyrrolidone, imidazopyridine, pyrazolopyrimidine, minor tranquilizers, melatonin agonists and antagonists, melatoninergic agents, benzodiazepines, barbiturates, 5HT-2 antagonists, and the like. Examples include: adinazolan, allobarbital, alonimid, alprazolam, amitriptyline, amobarbital, amoxapine, bentazepam, tacitin, brotizolam, bupropion, buspirone, butabarbital, butalbital, capuride, carbocloral, chloral betaine, chloral hydrate, hydrate), chlorodyne, clomipramine, clonazepam, domperidone, methaminodiazepoxide, cloretate, clozapine, cyprazepam, desipramine, dexclamo, diazepam, chloralsalicylamide, divalproexacid), diphenhydramine, doxepin, estazolam, ethchlorvynol, etomidate, fenobam, flunitrazepam, flurazepam, fluvoxamine, fluoxetine, fosazepam, glutethimide, halazepam ), hydroxyzine, imipramine, lithium, orazepam, lormetazepam, maprotiline, mecloqualone, melatonin, methylphenobarbital, meprobamate, methaqualone, midaflur, midazolam, nefazodone, nivolumab nisobamate, nitrazepam, nortriptyline, oxezepam, paraldehyde, paroxetine, pentobarbital, perlapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, isopropyl Phenol, protriptyline, quazepam, reclazepam, rolipram, secobarbital, sertraline, suproclone, temazepam, thioridazine, tracazolate, tranylcypromine, trazodone, triazole

[00135] Examples of the present invention include benzodiazepine, trepipam, tricetamide, trichloroethyl phosphate, trifluoperazine, trimetozine, trimeprimine, uldazepam, venlafaxine, zaleplon, zolazepam, zolpidem, and salts and compositions thereof, and the like. Alternatively, physical methods such as light therapy or electrical stimulation may be used during administration of the compounds disclosed herein. In addition, the compounds of the present invention can be administered as prodrugs. As used herein, a "prodrug" of a compound of the present invention is a functional derivative of the compound that, when administered to a patient, ultimately releases the compound of the present invention in vivo. Administration of the compound of the present invention as a prodrug allows one of ordinary skill in the art to perform one or more of the following: (a) modifying the onset of the compound's action in vivo; (b) modifying the duration of the compound's action in vivo; (c) modifying the compound's transport or distribution in vivo; (d) modifying the compound's solubility in vivo; and (e) overcoming side effects or other difficulties encountered by the compound. Typical functional derivatives used to prepare prodrugs include modifications of the compound that are chemically or enzymatically cleaved in vivo. Such modifications (including the preparation of phosphates, amides, esters, thioesters, carbonates, and carbamates) are well known to those skilled in the art. Uses of compounds and pharmaceutical compositions The compounds or pharmaceutical compositions disclosed herein are effective as NMDA receptor antagonists, and are useful for treating or preventing neurological and psychiatric diseases associated with NMDA receptors, and can be used to prepare drugs for antagonizing NMDA receptors. All diseases related to NMDA receptors can be selected from all types of neurological and psychiatric disorders or diseases. In one embodiment, diseases associated with NMDA receptors include depression, anxiety disorders, seasonal affective disorder, mania, bipolar disorder, obsessive-compulsive disorder, insomnia and fatigue caused by jet lag, schizophrenia, seizures, panic attacks, depression, alcohol addiction, drug addiction, alcoholism, drug abuse, drug withdrawal symptoms, insomnia, psychotic disorders, epilepsy, sleep disorders, sleep apnea syndrome, mandatory eating disorder, fibromyalgia, stress, obesity, Parkinson's disease, cognitive impairment, memory disorders, premenstrual syndrome, migraine, memory loss, Alzheimer's disease, and or asymptomatic diseases or diseases associated with normal or pathological aging. It will be appreciated that certain environmental conditions, such as stress or fear (wherein stress may be from social stressors such as social pressure, or physical sources such as physical stress, including stress resulting from fear), may promote or accelerate any of the above-mentioned symptoms or diseases, and that the compounds disclosed herein are particularly useful for treating symptoms and diseases that are modulated by these environments. In addition to being useful for human treatment, the compounds of the present invention and their compositions can also be used in veterinary animal treatments, such as pets, wild animals, and farm animals. In other embodiments, the animals disclosed herein include horses, dogs, and cats. As used herein, the compounds disclosed herein include pharmaceutically acceptable derivatives thereof. Preferred embodiments of the present invention General synthesis procedures The following examples are provided so that the present invention may be more fully understood. However, it should be understood that these embodiments are merely methods for implementing the present invention, and the present invention is not limited to these embodiments. Generally, the compounds disclosed herein can be prepared by the methods described herein, wherein the substituents are as defined above for Formula (Ia) or Formula (Ib), unless otherwise indicated. The following non-limiting schemes and examples are provided to further illustrate the present invention. Those skilled in the art will recognize that the chemical reactions described can be readily adapted to prepare many other compounds disclosed herein, and alternative methods for preparing the compounds disclosed herein are considered to be within the scope of the disclosure. Those skilled in the art will recognize that the starting materials can be varied and additional steps employed to prepare the compounds encompassed by the present invention, as demonstrated in the following examples. In some cases, it may be necessary to protect certain reactive functions to achieve some of the transformations described above. Generally, the need for such protecting groups and the conditions required to attach and remove these groups are readily apparent to those skilled in the art of organic synthesis. For example, the synthesis of non-exemplified compounds according to the present invention can be successfully performed by modifications readily apparent to those skilled in the art, such as by appropriately protecting interfering groups, by utilizing other suitable reagents known in the art in addition to those described, and / or by making routine modifications to the reaction conditions. Alternatively, known reaction conditions or reactions disclosed herein will be recognized as having applicability to preparing other compounds disclosed herein. In the examples described below, all temperatures are in degrees Celsius unless otherwise stated. Reagents were purchased from commercial suppliers such as Aldrich Chemical Company, Arcos Chemical Company, Alfa Aesar Chemical Company, and J&K Chemical Company and used without further purification unless otherwise stated. Preparation of compounds The compounds of the present invention (including salts, esters, hydrates or solvates thereof) can be prepared using any known organic synthesis technique and can be synthesized according to a variety of possible synthetic routes. The reaction of preparing the compounds of the present invention can be carried out in a suitable solvent, which can be easily selected by those skilled in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the raw materials (reactants), intermediates or products at the temperature at which the reaction is carried out, for example, in a temperature range from the freezing temperature of the solvent to the boiling temperature of the solvent. A given reaction can be carried out in a solvent or a mixture of more than one solvent. Depending on the specific reactions steps, the technician can select a suitable solvent for a particular reaction step. The reaction can be monitored by any suitable method known in the art. For example, the reaction can be monitored by spectroscopic means such as nuclear magnetic resonance spectroscopy (e.g., 1 H or 13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible light), mass spectrometry, or by chromatographic methods such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LCMS), or thin layer chromatography (TLC) to monitor the formation of the product. One skilled in the art can purify the compound by various methods, including high performance liquid chromatography (HPLC) ("Preparative LC-MS Purification: Improved Compound Specific Method Optimization" Karl F. Blom, Brian Glass, Richard Sparks, Andrew P. Combs J. Combi. Chem. 2004, 6(6), 874-883, the entire contents of which are incorporated herein by reference) and normal phase silica chromatography. The compounds of the present invention can be synthesized using the following methods, together with synthetic methods known in the field of synthetic organic chemistry or variations thereof as understood by those of ordinary skill in the art. Preferred methods include, but are not limited to, those described below. Specifically, the compounds of formula (Ia) to (Vd) of the present invention can be synthesized by following the steps outlined in the exemplary general synthetic schemes listed below, while the abbreviations of the reactants or the abbreviations of the chemical groups of the reactants included in the synthetic schemes are defined in the Examples. In general, the synthesis of compounds having formula (IIa) or (IIb) can be carried out according to the following synthetic methods, but are not limited to the methods described. An example of formula (IIa) is shown below. R 1 Can 、 、 、 、 、 、 、 、 . R 1 Can 、 、 、 . R 1 Can 、 、 、 、 、 、 、 、 、 、 . R 1 Can . R 1 Can 、 、 、 、 、 、 . In general, the synthesis of compounds having formula (IIIa) or (IIIb) can be carried out according to the following synthetic methods, but are not limited to the methods described. An example of formula (IIIa) is shown below. R 2 Can 、 、 . R 2 Can 、 、 、 、 、 、 、 . R 2 Can 、 、 . In general, the synthesis of compounds of formula (IVa) or (IVb) can be carried out according to the following synthetic methods, but are not limited to the methods described. An example of formula (IVa) is shown below. Can 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 . Can 、 、 . Can 、 、 、 、 、 、 、 、 . In general, the synthesis of compounds having formula (Va) to (Vd) can be carried out according to the following synthetic methods, but are not limited to these methods described. Examples of formula (Va) or (Vb) are shown below. ,or Preparation and characterization of exemplary compounds The compounds encompassed by the present invention can be prepared via various schemes. Detailed preparation methods for 108 exemplary compounds via various schemes are described below, along with characterization results. Unless otherwise noted, all reagents were purchased from commercial suppliers without further purification. Solvent drying was performed using standard methods when necessary. Plates used for thin-layer chromatography (TLC) were pre-coated E. Merck silica gel 60F254 (0.24 nm thickness) on aluminum plates, which were then visualized under UV light (365 nm and 254 nm) or by staining with 5% dodecyl phosphate in ethanol and subsequent heating. Column chromatography was performed using silica gel (200-400 mesh) from a commercial supplier. 1 H NMR spectra were recorded at room temperature on a BRUKER AVANCE III HD 500 MHz NMR spectrometer and a BRUKER AVANCE III HD 600 MHz NMR spectrometer. 1 Reference for HNMR (CDCl 3, 7.26 ppm; CD 3OD, 3.31 ppm; DMSO- d 6 , 2.50 ppm; acetone- d 6 ,2.05 ppm; D 2O, 4.79 ppm). The following abbreviations are used to explain multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, br. s = broad singlet, dd = doublet doublet, td = triplet doublet, dt = doublet triplet, dq = doublet quartet, m = multiplet. Other abbreviations used in the experimental details are as follows: δ = downfield chemical shift from tetramethylsilane in ppm, Ar = aryl, Ac = acyl, Boc = tert-butyloxycarbonyl, Bn = benzyl, DCM = dichloromethane, DCE = dichloroethane, DMF = N, N′-dimethylformamide, NMP = N-methyl-2-pyrrolidone, DIBAL-H = diisobutylaluminum hydride, DIPEA = diisopropylethylamine, DMAP = 4-(dimethylamino)pyridine, DMSO = dimethylsulfoxide, HATU = 1-[bis(dimethylamino)methylene]-1-fluorophosphate H-1,2,3-triazolo[4,5- b] Pyridinium 3-oxide, HOBT = 1-hydroxybenzotriazole, EA = ethyl acetate, Et = ethyl, Me = methyl, Hz = Hertz, HPLC = high performance liquid chromatography, J = coupling constant (in NMR), min = minute, h = hour, NMR = nuclear magnetic resonance, NBS = N-bromosuccinimide, NCS = N-chlorosuccinimide, prep = preparative, PE = petroleum ether, s-Bu = sec-butyl, t-Bu = tert-butyl, iPr = isopropyl, TBAF = tetrabutylammonium fluoride, tert = tert-butyl ether, TFA = trifluoroacetic acid, THF = tetrahydrofuran, MTBE = methyl tert-butyl ether, TLC = thin layer chromatography. Example It should be noted that the embodiments of the present invention described in detail below are merely examples for explaining the present invention and should not be construed as limiting the present invention. The embodiments without specific techniques or conditions can be implemented according to the techniques or conditions in the literature of this area or according to product specifications. Reagents or instruments without manufacturers can be obtained by conventional purchase. Those with ordinary skill in the art will recognize that starting materials can be changed and additional steps can be adopted to prepare the compounds encompassed by the present invention, as demonstrated in the following examples. Example 1 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 3- Hydroxyl -2-( Hydroxymethyl )-2- Methylpropional (A-1) At 0℃, SK-Cetamine Hydrochloride To a solution of 1 (274 mg, 1.0 mmol) and DIPEA (260 mg, 1.0 mmol) in DCM (10 mL) was slowly added 1-chloroethyl chloroformate (172 mg, 1.2 mmol). The reaction was stirred at 25 °C for 1.5 h. The reaction mixture was diluted with DCM (10 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was purified by MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (1 / 1 to 5 / 1) to give 276 mg (79% yield) of the compound as a white solid. 2. 1 HNMR (500 MHz, CDCl 3) δ = 1.60-1.96 (m, 6H), 1.99-2.10 (m, 1H), 2.32-2.56 (m, 1H), 2.57-2.63 (m, 1H), 2.67-2.84 (m, 1H), 3.01-3.07 (m, 3H), 3.22-3.40 (m, 1H), 6.48-6.60 (m, 1H), 6.91-7.04 (m, 1H), 7.22-7.30 (m, 2H), 7.43-7.49 (m, 1H). Towards compounds To a solution of 2 (150 mg, 0.44 mmol), NaI (65 mg, 0.44 mmol) and 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (292 mg, 2.18 mmol) in acetone (1.7 mL) was added Et 3N (0.31 mL, 2.18 mmol). The reaction was stirred at 25 °C for 5 h. The reaction mixture was concentrated and redissolved in EA (20 mL) and washed with H 2O (8 mL), saturated NaHCO 3 aqueous solution (2 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 6) to give 95 mg (49% yield) of the title compound ( A-1). 1 HNMR (500MHz, DMSO- d 6 ) δ = 1.02 (br. s, 3H), 1.46 (br. s, 3H), 1.68 (br. s, 3H), 1.99 (br. s, 1H), 2.26-2.37 (m, 2H), 2.50-2.65 (m, 1H), 2.95 (d, J= 9.0 Hz, 3H), 3.10-3.18 (m, 1H), 3.44-3.52 (m, 4H), 4.72 (m, 2H), 6.61 (q, J = 5.4 Hz, 1H), 6.96 (d, J= 7.1 Hz, 1H), 7.30 (m, 2H), 7.46 (m, 1H). MS (ESI): [M + H] + = 442.2. Example 2 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl (2 S)-5- Pendant oxypyrrolidine -2- Formate (A-2) Towards compounds 2 (100 mg, 0.29 mmol), NaI (43 mg, 0.29 mmol) and ( To a solution of S)-5-oxopyrrolidine-2-carboxylic acid (188 mg, 1.46 mmol) in acetone (1.2 mL) was added Et 3N (0.20 mL, 1.46 mmol). The reaction was stirred at 25 °C for 5 h and then concentrated. The mixture was diluted with EA (20 mL) and filtered. The filtrate was concentrated and then purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 6) to give 50 mg (39% yield) of the title compound ( A-2). 1 HNMR (500 MHz, CDCl 3) δ = 1.48 (br. s, 3H), 1.73 (m, 2H), 1.88 (br. s, 1H), 2.01 (m, 1H), 2.27-2.44 (m, 5H), 2.54-2.59 (m, 1H), 2.66-2.71 (m, 1H), 3.02 (br. s, 3H), 3.29-3.33 (m, 1H), 4.19-4.25 (m, 1H), 6.22-6.57 (m, 1H), 6.73-6.79 (m, 1H), 6.97 (br. s, 1H), 7.23-7.27 (m, 2H), 7.44 (m, 1H). MS (ESI): [M + H] + = 437.2. Example 3 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl Acetylglycinate (A-3) Towards compounds To a solution of 2 (172 mg, 0.5 mmol), NaI (75 mg, 0.5 mmol) and acetylglycine (176 mg, 1.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (10 mL) and washed with saturated NaHCO 3 aqueous solution (10 mL) and brine (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 2) to give 110 mg (35% yield) of the title compound as a white foam ( A-3). 1 HNMR (500 MHz, CD 3OD) δ = 1.51 (br. s, 3H), 1.77-1.83 (m, 3H), 1.99-2.01 (m, 3H), 2.01-2.06 (m, 1H), 2.33-2.46 (m, 2H), 2.67-2.82 (m, 1H), 3.03-3.05 (m, 3H), 3.36 (m, 1H), 3.87-3.97 (m, 2H), 6.73-6.77 (m, 1H), 7.03-7.05 (m, 1H), 7.39-7.45 (m, 2H), 7.45-7.47 (m, 1H). MS (ESI): [M + H] + = 425.3. Example 4 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 2-(3- Methyloxetane -3- base ) Acetate (A-4) Towards compounds To a solution of 2 (262 mg, 0.76 mmol), NaI (114 mg, 0.76 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (296 mg, 2.28 mmol) in acetone (9 mL) was added Et 3N (0.53 mL, 3.8 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered, and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give a yellow oil. Diethyl ether (3 mL) was added, filtered, and the solid was washed with cold diethyl ether to give 102 mg (31% yield) of the title compound ( A-4). 1 HNMR (500 MHz, CD 3OD) δ = 1.38 (s, 3H), 1.48 (br. s, 3H), 1.76-1.84 (m, 3H), 2.03-2.06 (m, 1H), 2.36 (d, J = 15.2 Hz, 1H), 2.46 (d, J= 13.5 Hz, 1H), 2.70-2.73 (m, 1H), 2.73 (s, 2H), 3.04 (s, 3H), 3.31-3.36 (m, 1H), 4.36-4.38 (m, 2H), 4.59-4.61 (m, 2H), 6.69-6.72 (m, 1H), 7.05-7.08 (m, 1H), 7.29-7.31 (m, 2H), 7.45-7.47 (m, 1H). MS (ESI): [M + H] + = 438.4. The filtrate was concentrated to an oil and stored at -20°C to give a sticky solid. The mixture was diluted with ether (2 mL) and the filtrate was collected. The filtrate was concentrated to give 40 mg (12% yield) of the compound as a colorless oil. A-4 Isomers. 1 HNMR (500 MHz, CD 3OD) δ = 1.32-1.40 (m, 3H), 1.49 (br. s, 3H), 1.72-1.92 (m, 3H), 2.03-2.06 (m, 1H), 2.41 (d, J = 11.8 Hz, 1H), 2.49 (d, J= 11.7 Hz, 1H), 2.63-2.74 (m, 2H), 2.75-2.84 (m, 1H), 3.03 (s, 3H), 3.33-3.36 (m, 1H), 4.33-4.36 (m, 2H), 4.57-4.60 (m, 2H), 6.71-6.73 (m, 1H), 7.02-7.04 (m, 1H), 7.29-7.31 (m, 2H), 7.45-7.47 (m, 1H). Example 5 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl acetyl -L- Alanine (A-5) Towards compounds 2 (172 mg, 0.5 mmol), NaI (150 mg, 1.0 mmol) and ( To a solution of S)-2-acetamidopropionic acid (328 mg, 2.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 149 mg (68% yield) of the title compound as a white foam ( A-5). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.13-1.28 (m, 3H), 1.31-1.59 (m, 3H), 1.60-1.79 (m, 3H), 1.80-1.90 (m, 4H), 2.21-2.42 (m, 2H), 2.53-2.75 (m, 1H), 2.96-2.98 (m, 3H), 3.06-3.21 (m, 1H), 4.14-4.29 (m, 1H), 6.55-6.65 (m, 1H), 6.91-7.01 (m, 1H), 7.28-7.40 (m, 2H), 7.42-7.53 (m, 1H), 8.15-8.41 (m, 1H). MS (ESI): [M + H] + = 439.1. Example 6 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl acetyl -L- Valine esters (A-6) Towards compounds 2 (172 mg, 0.5 mmol), NaI (150 mg, 1.0 mmol) and ( To a solution of S)-2-acetamido-3-methylbutanoic acid (239 mg, 1.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 159 mg (68% yield) of the title compound as a white foam ( A-6). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.70-0.95 (m, 6H), 1.30-1.55 (m, 3H), 1.60-1.79 (m, 3H), 1.88 (s, 3H), 1.90-2.08 (m, 1H), 2.22-2.41 (m, 2H), 2.55-2.70 (m, 1H), 2.95-2.97 (m, 3H), 3.05-3.20 (m, 2H), 4.10-4.25 (m, 1H), 6.55-6.78 (m, 1H), 6.92-7.05 (m, 1H), 7.25-7.43 (m, 2H), 7.45-7.55 (m, 1H), 8.10-8.35 (m, 1H). MS (ESI): [M + H] + = 467.3. Example 7 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 3- Hydroxyl -2-( Hydroxymethyl ) Propionate (A-7) Towards compounds To a solution of 2 (172 mg, 0.5 mmol), NaI (75 mg, 0.5 mmol) and 2-phenyl-1,3-dioxane-5-carboxylic acid (520 mg, 2.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (10 mL) and washed with saturated NaHCO 3 aqueous solution (10 mL) and brine (10 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 175 mg (68% yield) of the compound as a white foam. 3. 1 HNMR (500 MHz, CD 3OD) δ = 1.51 (br. s, 3H), 1.76-1.81 (m, 3H), 2.05-2.08 (m, 1H), 2.35-2.50 (m, 2H), 2.70-2.81 (m, 1H), 3.04-3.10 (m, 4H), 3.36-3.39 (m, 1H), 3.93-4.02 (m, 2H), 4.36-4.39 (m, 2H), 5.42 (s, 1H), 6.70-6.73 (m, 1H), 7.04-7.08 (m, 1H), 7.29-7.35 (m, 5H), 7.42-7.47 (m, 3H). MS (ESI): [M + H] + = 516.3. Towards compounds To a solution of 3 (100 mg, 0.19 mmol) in EA (10 mL) was added Pd(OH) 2 / C (11 mg). The reaction was carried out at 25°C, H 2 atmosphere for 50 min. The reaction was filtered through a Celite pad and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 40 mg (49% yield) of the title compound as a white foam ( A-7). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.47 (br. s, 3H), 1.76-1.80 (m, 3H), 2.37-2.40 (m, 2H), 2.70-2.73 (m, 2H), 2.87-3.02 (m, 3H), 3.23-3.34 (m, 1H), 3.77-3.83 (m, 5H), 6.72-6.75 (m, 1H), 7.09-7.11 (m, 1H), 7.28-7.34 (m, 2H), 7.43-7.45 (m, 1H). MS (ESI): [M + H] + = 428.1. Example 8 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 2-(((3- Methyloxetane -3- base ) methyl ) sulfinyl group ) Acetate (A-8) To a solution of compound 2 (172 mg, 0.5 mmol), NaI (75 mg, 0.5 mmol), and 2-(((3-methyloxetan-3-yl)methyl)thio)acetic acid (264 mg, 1.5 mmol) in acetone (6 mL) was added triethylamine (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 2 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 1) to give 180 mg (74% yield) of the compound as a yellow oil. 4. 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.20-1.35 (m, 3H), 1.40-1.65 (m, 3H), 1.70-1.90 (m, 3H), 2.30-2.60 (m, 3H), 2.65-2.80 (m, 1H), 2.95-3.00 (m, 2H), 3.04-3.07 (m, 3H), 3.20-3.45 (m, 3H), 4.20-4.30 (m, 2H), 4.35-4.50 (m, 2H), 6.75-6.85 (m, 1H), 7.05-7.15 (m, 1H), 7.25-7.40 (m, 2H), 7.45-7.50 (m, 1H). MS (ESI): [M + H] + = 484.1. At 0°C, the compound To a solution of 4 (140 mg, 0.29 mmol) in MeOH (1.4 mL) was added dropwise NaIO 4 (62 mg, 0.29 mmol) of H 2O (0.7 mL) solution. The reaction was stirred at 25 °C for 16 h, filtered, and the filtrate was collected. The filtrate was concentrated and purified on a silica gel column eluting with DCM / MeOH (100% DCM to 98 / 2) to give 38 mg (26% yield) of the title compound as a white foam ( A-8). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.43-1.51 (m, 6H), 1.64-1.70 (m, 3H), 1.95-1.99 (m, 1H), 2.30-2.33 (m, 2H), 2.55-2.61 (m, 1H), 2.96-3.03 (m, 4H), 3.11-3.14 (m, 1H), 3.40-3.44 (m, 1H), 3.98-4.10 (m, 2H), 4.21-4.28 (m, 2H), 4.48-4.50 (m, 1H), 4.59-4.62 (m, 1H), 6.69-6.71 (m, 1H), 6.97-6.99 (m, 1H), 7.33-7.35 (m, 2H), 7.46-7.48 (m, 1H). MS (ESI): [M + H] + = 500.1. Example 9 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 2-(((3- Methyloxetane -3- base ) methyl ) Sulfonyl ) Acetate (A-9) At 0°C, the compound To a solution of 4 (141 mg, 0.29 mmol) in MeOH (1.1 mL) was added dropwise Oxone (potassium peroxymonosulfate complex) (356 mg, 0.58 mmol) in H 2O (0.9 mL) solution. The reaction was stirred at 25 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 42 mg (29% yield) of the title compound as a white foam ( A-9). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.19-1.21 (m, 2H), 1.59-1.62 (m, 6H), 1.78-1.93 (m, 4H), 2.45-2.57 (m, 2H), 3.04-3.08 (m, 3H), 3.20-3.40 (m, 1H), 3.79-3.82 (m, 2H), 4.25-4.30 (m, 3H), 4.53-4.67 (m, 2H), 6.81-6.84 (m, 1H), 7.09-7.11 (m, 1H), 7.31-7.37 (m, 2H), 7.37-7.46 (m, 1H). MS (ESI): [M + H] + = 516.2. Example 10 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl (2 R)-2- Hydroxypropionate (A-10) Towards compounds 2 (172 mg, 0.5 mmol), NaI (75 mg, 0.5 mmol) and To a solution of R-lactic acid (227 mg, 2.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 3.5 h. The reaction was concentrated and redissolved in DCM (10 mL) and washed with H 2O (10 mL) and brine (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 1) to give 100 mg (50% yield) of the title compound as a white foam ( A-10). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.20-1.26 (m, 3H), 1.45-1.47 (m, 3H), 1.65-1.69 (m, 3H), 1.98 (br. s, 1H), 2.29-2.36 (m, 2H), 2.58 (br. s, 1H), 2.95-2.98 (m, 3H), 3.12-3.16 (m, 1H), 4.11-4.13 (m, 1H), 5.47-5.56 (m, 1H), 6.62-6.65 (m,1H), 6.93-6.95 (m, 1H), 7.31-7.34 (m, 2H), 7.45-7.48 (m, 1H). MS (ESI): [M + H] + = 398.1. Example 11 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl (2 R)-2- Acetoxypropionate (A-11) Towards compounds 2 (172 mg, 0.5 mmol), NaI (79 mg, 0.525 mmol) and ( To a solution of R)-2-acetoxypropionic acid (172 mg, 0.5 mmol) in acetone (6 mL) was added Et 3N (0.35 mL, 2.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 65 / 35) to give 204 mg (93% yield) of the title compound as a white foam ( A-11). 1 HNMR (500 MHz, DMSO- d 6) δ = 1.20-1.55 (m, 6H), 1.56-1.69 (m, 4H), 2.06-2.10 (m, 3H), 2.25-2.42 (m, 2H), 2.55-2.65 (m, 1H), 2.97 (d, J =6.4 Hz, 3H), 3.05-3.21 (m, 1H), 4.85-5.02 (m, 1H), 6.60-6.70 (m, 1H), 6.90-7.05 (m, 1H), 7.21-7.39 (m, 2H), 7.41-7.48 (m, 1H). MS (ESI): [M + H] + = 440.0. Example 12 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl Nicotine esters (A-12) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and nicotinic acid (92 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 47 mg (47% yield) of the title compound as a white solid ( A-12). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.46-1.88 (m, 6H), 2.28-2.62 (m, 3H), 2.66-2.78 (m, 1H), 3.07-3.11 (m, 3H), 3.18-3.38 (m, 1H), 6.94-7.06 (m, 1H), 7.08-7.18 (m, 1H), 7.22-7.36 (m, 2H), 7.40-7.50 (m, 1H), 7.54-7.62 (m, 1H), 8.18-8.40 (m, 1H), 8.78-8.88 (m, 1H), 9.04-9.24 (m, 1H). MS (ESI): [M + H] + = 431.2. Example 13 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 3- Benzyl benzoate (A-13) Towards compounds To a solution of 2 (54 mg, 0.16 mmol), NaI (25 mg, 0.17 mmol) and 3-benzylbenzoic acid (100 mg, 0.47 mmol) in acetone (2 mL) was added Et 3N (0.11 mL, 0.78 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 60 mg (74% yield) of the title compound as a colorless solid ( A-13). 1 HNMR (500 MHz, CD 3OD) δ = 1.51-1.69 (m, 2H), 1.70-1.88 (m, 3H), 1.97-2.12 (m, 1H), 2.29-2.48 (m, 2H), 2.68-2.80 (m, 1H), 3.05 (d, J =12.9 Hz, 3H), 3.24-3.30 (m, 1H), 3.32-3.44 (m, 1H), 4.05 (d, J= 4.3 Hz, 2H), 6.92-6.97 (m, 1H), 7.01-7.08 (m, 1H), 7.13-7.22 (m, 4H), 7.23-7.33 (m, 3H), 7.35-7.45 (m, 2H), 7.46-7.51 (m, 1H), 7.76-7.92 (m, 2H). MS (ESI): [M + H] + = 520.4. Example 14 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl Benzo [d][1,3] Two evil -5- Formate (A-14) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (39 mg, 0.26 mmol) and benzo[d][1,3]dioxane-5-carboxylic acid (125 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 7 / 3) to give 110 mg (93% yield) of the title compound ( A-14). 1 HNMR (500 MHz, CD 3OD) δ = 1.43-1.70 (m, 3H), 1.71-1.90 (m, 3H), 2.03-2.15 (m, 1H), 2.28-2.52 (m, 2H), 2.65-2.87 (m, 1H), 3.07 (d, J =15.4 Hz, 3H), 3.34-3.45 (m, 1H), 6.08 (s, 2H), 6.87-6.96 (m, 2H), 7.02-7.12 (m, 1H), 7.22-7.33 (m, 2H), 7.34-7.50 (m, 2H), 7.57-7.72 (m, 1H). MS (ESI): [M + H] + = 474.3. Example 15 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 1- Methylpiperidine -4- Formate (A-15) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 1-methylpiperidine-4-carboxylic acid (117 mg, 0.82 mmol) in DMSO (1 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was stirred at 25 °C for 3 h. The reaction was concentrated and then purified on a silica gel column eluting with DCM / MeOH (100% hexanes to 95 / 5) to give 23 mg (20% yield) of the title compound ( A-15). 1 HNMR (600 MHz, CD 3OD) δ = 1.22-1.36 (m, 1H), 1.38-1.66 (m, 3H), 1.72-1.90 (m, 5H), 1.92-2.02 (m, 2H), 2.06-2.12 (m, 1H), 2.28-2.62 (m, 8H), 2.68-2.82 (m, 1H), 2.86-3.14 (m, 2H), 3.05 -3.07 (m, 2H), 3.31-3.40 (m, 1H), 6.68-6.77 (m, 1H), 6.98-7.08 (m, 1H), 7.26-7.37 (m, 2H), 7.44-7.50 (m, 1H). MS (ESI): [M + H] + = 451.2. Example 16 : 1-( Isonicotinoyl ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-16) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and isonicotinic acid (92 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 50 mg (46% yield) of the title compound ( A-16). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.50-1.87 (m, 6H), 2.32-2.54 (m, 3H), 2.65-2.78 (m, 1H), 3.04-3.13 (m, 3H), 3.17-3.35 (m, 1H), 6.96-7.04 (m, 1H), 7.07-7.17 (m, 1H), 7.23-7.36 (m, 2H), 7.39-7.48 (m, 1H), 7.77-7.92 (m, 2H), 8.78-8.86 (m, 2H). MS (ESI): [M + H] + = 430.8. Example 17 : 1-(2-( Isobutylamide ) acetyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-17) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 2-(isobutylamido)acetic acid (109 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 57 mg (50% yield) of the title compound ( A-17). 1 HNMR (500 MHz, CD 3OD) δ = 1.12-1.16 (m, 6H), 1.52 (s, 2H), 1.72-1.89 (m, 3H), 2.03-2.12 (m, 1H), 2.32-2.56 (m, 3H), 2.66-2.85 (m, 1H), 3.00-3.08 (m, 3H), 3.25-3.40 (m, 2H), 3.84-4.01 (m, 2H), 6.70-6.78 (m, 1H), 7.01-7.10 (m, 1H), 7.26-7.35 (m, 2H), 7.44-7.47 (m, 1H). MS (ESI): [M + H] + = 452.6. Example 18 : 1-(3- Acetamidopropionyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-18) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 3-acetamidopropionic acid (98 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 22 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 2) to give 20 mg (18% yield) of the title compound ( A-18). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.30-1.75 (m, 7H), 1.78 (d, J= 2.4 Hz, 3H), 1.90-2.05 (m, 1H), 2.20-2.45 (m, 3H), 2.55-2.65 (m, 1H), 2.95-2.97 (m, 3H), 3.00-3.25 (m, 3H), 6.55-6.70 (m, 1H), 6.90-7.10 (m, 1H), 7.25-7.60 (m, 3H), 7.80-7.90 (m, 1H). MS (ESI): [M + H] + = 438.9. Example 19 : 1-(4- Acetamidobutyryloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-19) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 4-acetaminobutyric acid (109 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 22 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 2) to give 72 mg (64% yield) of the title compound as a white foam ( A-19). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.30-1.55 (m, 3H), 1.56-1.76 (m, 5H), 1.78 (d, J= 2.7 Hz, 3H), 1.94-2.04 (m, 1H), 2.23-2.40 (m, 4H), 2.54-2.65 (m, 1H), 2.95-2.97 (m, 3H), 2.99-3.07 (m, 2H), 3.09-3.19 (m, 1H), 6.58-6.66 (m, 1H), 6.92-7.00 (m, 1H), 7.28-7.36 (m, 2H), 7.44-7.49 (m, 1H), 7.80-7.88 (m, 1H). MS (ESI): [M + H] + = 452.9. Example 20 : (2-(3- Methyloxetane -3- base ) acetyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-20) At 0℃, SK-Cetamine Hydrochloride To a solution of 1 (102 mg, 0.375 mmol) and DIPEA (97 mg, 0.75 mmol) in DCM (3.75 mL) was slowly added chloromethyl chloroformate (121 mg, 0.94 mmol). The reaction was stirred at 25 °C for 24 h. The reaction was diluted with DCM (5 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was purified by MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 9 / 1) to give 93 mg (75% yield) of the compound as a white solid. 5. 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.68-1.90 (m, 4H), 2.42-2.49 (m, 1H), 2.50-2.59 (m, 1H), 2.65-2.75 (m, 1H), 3.07 (s, 3H), 3.20-3.33 (m, 1H), 5.88 (s, 2H), 7.05-7.13 (m, 1H), 7.28-7.36 (m, 2H), 7.43-7.50 (m, 1H). MS (ESI): [M + H] + = 330.2. Towards compounds To a solution of 5 (82 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (98 mg, 0.75 mmol) in acetone (3 mL) was added K 2CO 3 (173 mg, 1.25 mmol). The reaction was heated to 70 °C for 2 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 2) to give 84 mg (80% yield) of the title compound ( A-20). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.39 (s, 3H), 1.68-1.88 (m, 3H), 1.98-2.09 (m, 1H), 2.41-2.53 (m, 2H), 2.65-2.73 (m, 1H), 2.77 (s, 2H), 3.03 (s, 3H), 3.19-3.32 (m, 1H), 4.28 (d, J = 5.85 Hz, 2H), 4.50 (d, J= 5.85 Hz, 2H), 5.66-5.86 (m, 2H), 7.05-7.11 (m, 1H), 7.28-7.35 (m, 2H), 7.42-7.48 (m, 1H). MS (ESI): [M + H] + = 424.5. Example twenty one : 1-( Oxetanes -3- carbonyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-21) Towards compounds To a solution of 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and oxetane-3-carboxylic acid (77 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 40 mg (49% yield) of the title compound ( A-21). 1 HNMR (600 MHz, acetone- d 6 ) δ = 1.33-1.64 (m, 3H), 1.68-1.90 (m, 4H), 2.34-2.53 (m, 2H), 2.65-2.77 (m, 1H), 3.04-3.06 (m, 3H), 3.20-3.34 (m, 1H), 3.82-3.94 (m, 1H), 4.55-4.82 (m, 4H), 6.75-6.82 (m, 1H), 7.02-7.11 (m, 1H), 7.26-7.36 (m, 2H), 7.41-7.48 (m, 1H). MS (ESI): [M + H] + = 409.9. Example twenty two : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Propyl 2-(3- Methyloxetane -3- base ) Acetate (A-22) At 0℃, SK-Cetamine Hydrochloride To a solution of 1 (137 mg, 0.5 mmol) and DIPEA (130 mg, 1.0 mmol) in DCM (5 mL) was slowly added 1-chloroethyl chloroformate (94 mg, 0.6 mmol). The reaction was stirred at 25 °C for 16 h. The reaction was diluted with DCM (5 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was precipitated with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 10 / 1) to give 133 mg (74% yield) of the compound as a colorless oil. 6. 1 HNMR (600 MHz, CDCl 3) δ = 1.04-1.06 (m, 3H), 1.75-1.89 (m, 4H), 2.02-2.05 (m, 2H), 2.37-2.50 (m, 1H), 2.55-2.59 (m, 1H), 2.70-2.73 (m, 1H), 3.01-3.08 (m, 3H), 3.27-3.35 (m, 1H), 6.36-6.40 (m, 1H), 6.94-7.00 (m, 1H), 7.22-7.25 (m, 2H), 7.41-7.45 (m, 1H). Towards compounds To a solution of 6 (90 mg, 0.25 mmol), NaI (37 mg, 0.25 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (98 mg, 0.75 mmol) in acetone (1 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 10 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 1) to give 32 mg (28% yield) of the title compound as a yellow oil ( A-22). 1 HNMR (600 MHz, acetone- d 6 ) δ = 0.89-1.04 (m, 3H), 1.38-1.41 (m, 3H), 1.88-1.78 (m, 5H), 2.41-2.55 (m, 2H), 2.67-2.84 (m, 4H), 3.06-3.09 (m, 3H), 3.20-3.37 (m, 1H), 4.29-4.31 (m, 2H), 4.50-4.54 (m, 2H), 6.63-6.67 (m, 1H), 7.09-7.014 (m, 1H), 7.32-7.35 (m, 2H), 7.49-7.46 (m, 1H). MS (ESI): [M + H] + = 452.0. Example twenty three : 1-( Tetrahydro -2 H- Pyran -4- carbonyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-23) Towards compounds 2 (86 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and tetrahydro-2 To a solution of H-pyran-4-carboxylic acid (98 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 72 mg (66% yield) of the title compound as a white foam ( A-23). 1 HNMR (500 MHz, CD 3OD) δ = 1.51 (s, 3H), 1.61-1.91 (m, 7H), 2.03-2.12 (m, 1H), 2.32-2.52 (m, 2H), 2.56-2.65 (m, 1H), 2.67-2.83 (m, 1H), 3.05 (d, J =11.5 Hz, 3H), 3.32-3.39 (m, 1H), 3.40-3.50 (m, 2H), 3.81-3.94 (m, 2H), 6.69-6.75 (m, 1H), 6.99-7.08 (m, 1H), 7.26-7.32 (m, 2H), 7.43-7.48 (m, 1H). MS (ESI): [M + H] + = 438.1. Example twenty four : 1-(2-(3- Methyloxetane -3- base ) acetyloxy )-2- Methylpropyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-24) At 0℃, SK-Cetamine Hydrochloride To a solution of 1 (200 mg, 0.73 mmol) and DIPEA (0.25 mL, 1.46 mmol) in DCM (8 mL) was slowly added 1-chloro-2-methylpropyl chloroformate (312 mg, 1.83 mmol), and then stirred at 25 °C for 1 h. The reaction was diluted with DCM (5 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was purified by MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 9 / 1) to give 230 mg (85% yield) of the compound as a white solid. 7. 1 HNMR (600 MHz, acetone- d 6 ) δ = 0.75-1.27 (m, 6H), 1.68-1.90 (m, 3H), 2.38-2.58 (m, 2H), 2.65-2.77 (m, 1H), 2.83-2.85 (m, 2H), 3.08-3.12 (m, 3H), 3.18-3.36 (m, 1H), 6.35 (d, J= 4.3 Hz, 1H), 7.01-7.11 (m, 1H), 7.28-7.35 (m, 2H), 7.44-7.49 (m, 1H). MS (ESI): [M + H] + = 371.8. Towards compounds To a solution of 7 (93 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (98 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 5 h. The reaction was concentrated and dissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 15 mg (13% yield) of the title compound as a white foam ( A-24). 1 HNMR (600 MHz, CD 3OD) δ = 1.01 (s, 6H), 1.40 (s, 3H), 1.72-1.90 (m, 3H), 1.99-2.16 (m, 3H), 2.32-2.52 (m, 2H), 2.64-2.88 (m, 3H), 3.05 (d, J =20.2 Hz, 3H), 3.33-3.43 (m, 1H), 4.38 (dd, J =1.8, 6.0 Hz, 2H), 4.6 (d, J =5.8 Hz, 2H), 6.50 (dd, J =4.8, 7.8 Hz, 1H), 7.01-7.10 (m, 1H), 7.27-7.32 (m, 2H), 7.43-7.48 (m, 1H). MS (ESI): [M + H] + = 466.1. Example 25 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Propyl Acetylglycinate (A-25) Towards compounds To a solution of 6 (90 mg, 0.25 mmol), NaI (37 mg, 0.25 mmol) and acetylglycine (88 mg, 0.75 mmol) in acetone (1 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 10 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (1 / 0 to 1 / 2) to give 18 mg (16% yield) of the title compound ( A-25). 1 HNMR (600 MHz, acetone- d 6) δ = 0.86-1.04 (m, 3H), 1.74-1.84 (m, 4H), 1.94-1.95 (m, 3H), 2.06-2.07 (m, 3H), 2.37-2.49 (m, 2H), 2.67-2.79 (m, 1H), 3.03-3.07 (m, 3H), 3.21-3.34 (m, 1H), 3.85-3.94 (m, 1H), 3.99-4.05 (m, 1H), 6.62-6.66 (m, 1H), 7.06-7.09 (m, 1H), 7.28-7.35 (m, 2H), 7.45-7.44 (m, 1H). MS (ESI): [M + H] + = 439.0. Example 26 : 1-(2- acetamidoacetoxy )-2- Methylpropyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-26) Towards compounds To a solution of 7 (93 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and acetylglycine (88 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (2 / 3) to give 29 mg (28% yield) of the title compound as a colorless oil ( A-26). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.76-1.11 (m, 6H), 1.60-1.78 (m, 3H), 1.86 (d, J= 2.0 Hz, 3H), 1.95-2.05 (m, 1H), 2.26-2.40 (m, 2H), 2.52-2.68 (m, 1H), 2.65-2.98 (m, 3H), 3.04-3.20 (m, 1H), 3.71-3.97 (m, 3H), 6.38-6.47 (m, 1H), 6.89-6.99 (m, 1H), 7.28-7.36 (m, 2H), 7.43-7.49 (m, 1H), 8.33-8.43 (m, 1H). MS (ESI): [M + H] + = 453.3. Example 27 : ( Nicotine acyl group ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-27) Towards compounds To a solution of 5 (82 mg, 0.25 mmol), NaI (75 mg, 0.5 mmol) and nicotinic acid (92 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.18 mL, 1.25 mmol). The reaction was heated to 70 °C for 2 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (3 / 2) to give 32 mg (31% yield) of the title compound as a white solid ( A-27). 1 HNMR (600 MHz, acetone- d 6 ) δ = 1.66-1.87 (m, 3H), 1.97-2.20 (m, 1H), 2.36-2.55 (m, 2H), 2.67-2.75 (m, 1H), 3.07 (s, 3H), 3.20-3.32 (m, 1H), 5.86-6.18 (m, 2H), 7.07-7.13 (m, 1H), 7.21-7.32 (m, 2H), 7.40-7.46 (m, 1H), 7.56-7.62 (m, 1H), 8.30-8.39 (m, 1H), 8.82-8.89 (m, 1H), 9.12-9.20 (m, 1H). MS (ESI): [M + H] + = 416.9. Example 28 : 2-(2- Chlorophenyl )-2-( methyl ( methyl -d3) Amine ) Cyclohexane -1- ketone (A-28) Towards SK-Cetamine Hydrochloride 1 (68 mg, 0.25 mmol) and iodomethane- d 3 (109 mg, 0.75 mmol) and Cs 2CO A solution of 3 (163 mg, 0.5 mmol) in DMF (5 mL) was prepared. The reaction was stirred at 25 °C for 4 h. The reaction was diluted with DCM (5 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was precipitated with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 16 mg (23% yield) of the title compound as a yellow solid ( A-28). 1 HNMR (500 MHz, CD 3OD) δ = 1.58-1.48 (m, 1H), 1.80-1.62 (m, 3H), 2.03-1.95 (m, 1H), 2.19 (s, 3H), 2.51-2.40 (m, 1H), 2.66-2.56 (m, 1H), 3.20-3.09 (m, 1H), 7.41-7.35 (m, 1H), 7.52-7.43 (m, 2H), 7.62-7.56 (m, 1H). MS (ESI): [M + H] + = 255.0. Example 29 : (2- acetamidoacetoxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-29) Towards compounds To a solution of 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and 2-acetamidoacetic acid (53 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 25 mg (40% yield) of the title compound as a colorless gum ( A-29). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.61-1.77 (m, 3H), 1.87 (s, 3H), 1.95-2.00 (m, 1H), 2.29-2.37 (m, 2H), 2.54-2.63 (m, 1H), 2.96 (s, 3H), 3.08-3.17 (m, 1H), 3.81-3.90 (m, 2H), 5.62-5.78 (m, 2H), 6.93-6.98 (m, 1H), 7.29-7.38 (m, 2H), 7.44-7.48 (m, 1H), 8.36-8.43 (m, 1H). MS (ESI): [M + H] + = 411.1. Example 30 : (( S)-2- acetamido -3- Methylbutyryloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-30) Towards compounds 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and ( To a solution of S)-2-acetamido-3-methylbutanoic acid (72 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 65 mg (95% yield) of the title compound as a white foam ( A-30). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.82-0.97 (m, 6H) 1.54-1.77 (m, 3H), 1.88 (s, 3H), 1.92-2.07 (m, 2H), 2.29-2.37 (m, 2H), 2.52-2.60 (m, 1H), 2.95 (s, 3H), 3.06-3.17 (m, 1H), 4.09-4.16 (m, 1H), 5.60-5.85 (m, 2H), 6.89-6.99 (m, 1H), 7.26-7.37 (m, 2H), 7.42-7.50 (m, 1H), 8.19-8.29 (m, 1H). MS (ESI): [M + H] + = 453.1. Example 31 : (( S)-2- Acetamidopropionyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-31) Towards compounds 5 (50 mg, 0.15 mmol), NaI (46 mg, 0.3 mmol) and ( To a solution of S)-2-acetamidopropionic acid (60 mg, 0.46 mmol) in acetone (1.8 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 13 / 7) to give 52 mg (81% yield) of the title compound as a white foam ( A-31). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.22-1.30 (m, 3H), 1.60-1.82 (m, 3H), 1.84 (s, 3H), 1.93-2.00 (m, 1H), 2.30-2.37 (m, 2H), 2.54-2.60 (m, 1H), 2.96 (s, 3H), 3.09-3.16 (m, 1H), 4.16-4.24 (m, 1H), 5.60-5.80 (m, 2H), 6.94-7.00 (m, 1H), 7.30-7.36 (m, 2H), 7.44-7.49 (m, 1H), 8.38 (d, J = 6.0 Hz, 1H). MS (ESI): [M + H] + = 424.8. Example 32 : (2-( Isobutylamide ) acetyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-32) Towards compounds To a solution of 5 (50 mg, 0.15 mmol), NaI (46 mg, 0.3 mmol) and 2-(isobutylamido)acetic acid (66 mg, 0.46 mmol) in acetone (1.8 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 47 mg (70% yield) of the title compound as a white foam ( A-32). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.01 (d, J= 6.8 Hz, 6H), 1.62-1.76 (m, 3H), 1.94-2.01 (m, 1H), 2.29-2.38 (m, 2H), 2.39-2.46 (m, 1H), 2.55-2.63 (m, 1H), 2.99 (s, 3H), 3.08-3.16 (m, 1H), 3.85 (d, J= 5.3 Hz, 2H), 5.60-5.80 (m, 2H), 6.94-6.98 (m, 1H), 7.30-7.37 (m, 2H), 7.44-7.48 (m, 1H), 8.27 (t, J = 5.64 Hz, 1H). MS (ESI): [M + H] + = 439.2. Example 33 : (( S)-2-( Isobutylamide ) propionyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-33) Towards compounds 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and ( To a solution of S)-2-(isobutylamido)propionic acid (72 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 4 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 30 mg (44% yield) of the title compound as a white foam ( A-33). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.96-1.03 (m, 6H) 1.23-1.32 (m, 3H), 1.58-1.77 (m, 3H), 1.89-2.03 (m, 1H), 2.28-2.37 (m, 2H), 2.37-2.46 (m, 1H), 2.54-2.64 (m, 1H), 2.96 (s, 3H), 3.08-3.17 (m, 1H), 4.17-4.26 (m, 1H), 5.58-5.82 (m, 2H), 6.95-7.04 (m, 1H), 7.29-7.36 (m, 2H), 7.43-7.50 (m, 1H), 8.17-8.29 (m, 1H). MS (ESI): [M + H] + = 453.0. Example 34 : (( S)-2-( Isobutylamide )-3- Methylbutyryloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-34) Towards compounds 5 (50 mg, 0.15 mmol), NaI (46 mg, 0.3 mmol) and ( To a solution of 2-(isobutylamido)-3-methylbutanoic acid (102 mg, 0.46 mmol) in acetone (1.8 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 7 / 3) to give 67 mg (93% yield) of the title compound as a yellow foam ( A-34). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.85-0.94 (m, 6H), 0.96-1.02 (m, 6H), 1.55-1.65 (m, 1H), 1.66-1.76 (m, 2H), 1.92-1.99 (m, 1H), 2.00-2.08 (m, 1H), 2.31-2.40 (m, 2H), 2.52-2.60 (m, 2H), 2.95 (s, 3H), 3.08-3.17 (m, 1H), 4.14 (t, J= 6.8 Hz, 1H), 5.60-5.88 (m, 2H), 6.95-7.00 (m, 1H), 7.30-7.36 (m, 2H), 7.44-7.49 (m, 1H), 8.12 (d, J = 7.6 Hz, 1H). MS (ESI): [M + H] + = 481.1. Example 35 : (((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl L- Valine esters (A-35) Towards compounds 5 (150 mg, 0.46 mmol), NaI (137 mg, 0.9 mmol) and N-(tert-Butoxycarbonyl)- To a solution of L-valine (297 mg, 1.4 mmol) in acetone (5.4 mL) was added K 2CO 3 (315 mg, 2.3 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 191 mg (82% yield) of the compound as a white foam. 8. 1 HNMR (600 MHz, acetone- d 6 ) δ = 0.94-1.02 (m, 6H), 1.40 (s, 9H), 1.72-1.87 (m, 3H), 2.00-2.03 (m, 1H), 2.11-2.19 (m, 1H), 2.39-2.51 (m, 2H), 2.65-2.72 (m, 1H), 3.05 (s, 3H), 3.23-3.32 (m, 1H), 4.07-4.12 (m, 1H), 5.70-5.94 (m, 2H), 6.31 (br. s, 1H), 7.05-7.12 (m, 1H), 7.28-7.36 (m, 2H), 7.43-7.48 (m, 1H). MS (ESI): [M + H] + = 511.3. Towards compounds To a solution of 8 (71 mg, 0.14 mmol) in DCM (5 mL) was added TFA (0.19 mL, 2.5 mmol). The reaction was stirred at 25°C for 16 h. The reaction was concentrated to give 67 mg of the title compound ( A-35). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.92-0.99 (m, 6H), 1.56-1.78 (m, 3H), 1.92-1.99 (m, 1H), 2.10-2.20 (m, 1H), 2.32-2.43 (m, 2H), 2.53-2.62 (m, 1H), 2.97 (s, 3H), 3.06-3.17 (m, 1H), 4.02-4.10 (m, 1H), 5.68-5.86 (m, 1H), 5.87-6.05 (m, 1H), 6.95-7.01 (m, 1H), 7.30-7.37 (m, 2H), 7.45-7.51 (m, 1H), 8.45 (br. s, 3H). MS (ESI): [M + H] + = 411.2. Example 36 : ( S)-(((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl Glycinate (A-36) Towards compounds 5 (50 mg, 0.15 mmol), NaI (46 mg, 0.3 mmol) and N-(tert-Butoxycarbonyl)- To a solution of L-glycine (102 mg, 0.46 mmol) in acetone (1.8 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 7 / 3) to give 54 mg (76% yield) of the compound as a white foam. 9. 1 HNMR (600 MHz, acetone- d 6 ) δ = 1.42 (s, 9H), 1.69-1.87 (m, 3H), 1.99-2.03 (m, 1H), 2.38-2.51 (m, 2H), 2.66-2.74 (m, 1H), 3.04 (s, 3H), 3.22-3.32 (m, 1H), 3.82-3.92 (m, 2H), 5.70-5.88 (m, 2H), 6.44 (br. s, 1H), 7.05-7.11 (m, 1H), 7.28-7.37 (m, 2H), 7.43-7.48 (m, 1H). MS (ESI): [M + H] + = 469.1. Towards compounds To a solution of 9 (25 mg, 0.05 mmol) in DCM (1.9 mL) was added TFA (0.07 mL, 0.96 mmol). The reaction was stirred at 25°C for 16 h. The reaction was concentrated to give 25 mg of the title compound ( A-36). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.60-1.80 (m, 3H), 1.92-2.01 (m, 1H), 2.33-2.43 (m, 2H), 2.54-2.65 (m, 1H), 2.98 (s, 3H), 3.08-3.17 (m, 1H), 3.92 (br. s, 2H), 5.72-5.92 (m, 2H), 6.96-7.02 (m, 1H), 7.30-7.38 (m, 2H), 7.45-7.51 (m, 1H), 8.31 (br. s, 3H). MS (ESI): [M + H] + = 368.9. Example 37 : (((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl dimethyl -L- Valine esters (A-37) The compound ( A-35) TFA salt (52 mg, 0.1 mmol) was dissolved in MeOH (5.8 mL) and cooled to 0°C in an ice bath. Acetic acid (0.02 mL, 0.4 mmol) and NaBH 3CN (13 mg, 0.2 mmol) was added to the above solution and stirred at 0°C for 5 min. Formaldehyde (37%, in H 2O, 0.02 mmol), and the reaction mixture was stirred at 25 ° C for 2.5 h. The reaction was quenched with saturated NaHCO The mixture was quenched with 3% aqueous solution (5 mL) and diluted with water (5 mL). The aqueous layer was extracted with DCM (5 mL), and the organic layer was washed with brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give a solid. The solid was washed with hexane and then recrystallized from DCM and hexane at 4°C. After 16 h, the mixture was filtered and the filtrate was collected and concentrated to give 20 mg (46% yield) of the title compound ( A-37). 1 HNMR (600 MHz, acetone- d 6 ) δ = 0.89 (d, J = 6.5 Hz, 3H), 0.97 (d, J= 6.6 Hz, 3H), 1.72-1.87 (m, 3H), 1.96-2.03 (m, 2H), 2.30 (s, 6H), 2.40-2.46 (m, 1H), 2.46-2.53 (m, 1H), 2.66-2.73 (m, 1H), 2.74-2.78 (m, 1H), 3.04 (s, 3H), 3.22-3.29 (m, 1H), 5.80-5.90 (m, 2H), 7.05-7.09 (m, 1H), 7.27-7.34 (m, 2H), 7.44-7.48 (m, 1H). MS (ESI): [M + H] + = 439.5. Example 38 : (2-( N- Methylacetamido ) acetyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-38) Towards compounds 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and 2-( To a solution of N-methylacetamido)acetic acid (99 mg, 0.76 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 25 mg (39% yield) of the title compound as a white foam ( A-38). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.61-1.76 (m, 3H) 1.89-2.01 (m, 2H), 2.01-2.05 (m, 2H), 2.30-2.40 (m, 2H), 2.54-2.73 (m, 2H), 2.80 (s, 1H), 2.96 (s, 3H), 3.03 (s, 2H), 3.08-3.18 (m, 1H), 4.06-4.37 (m, 2H), 5.61-5.86 (m, 2H), 6.93-7.00 (m, 1H), 7.29-7.38 (m, 2H), 7.43-7.50 (m, 1H). MS (ESI): [M + H] + = 425.3. Example 39 : 1-(2-( N- Methylacetamido ) acetyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-39) Towards compounds 2 (50 mg, 0.15 mmol), NaI (43 mg, 0.29 mmol) and 2-( To a solution of N-methylacetamido)acetic acid (95 mg, 0.73 mmol) in acetone (2 mL) was added Et 3N (0.10 mL, 0.73 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 36 mg (57% yield) of the title compound as a white foam ( A-39). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.29-1.59 (m, 3H), 1.59-1.78 (m, 3H), 1.81-1.90 (m, 1H), 1.94-2.07 (m, 3H), 2.25-2.42 (m, 2H), 2.53-2.68 (m, 1H), 2.78 (s, 1H), 2.92-3.03 (m, 5H), 3.06-3.19 (m, 1H), 3.99-4.29 (m, 2H), 6.61-6.72 (m, 1H), 6.91-7.02 (m, 1H), 7.28-7.37 (m, 2H), 7.43-7.50 (m, 1H). MS (ESI): [M + H] + = 439.3. Example 40 : 1-(2-( Propionamide ) acetyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-40) Towards compounds To a solution of 2 (50 mg, 0.145 mmol), NaI (23 mg, 0.15 mmol) and 2-(propionamido)acetic acid (57 mg, 0.435 mmol) in acetone (1.8 mL) was added Et 3N (0.1 mL, 0.725 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 41 mg (65% yield) of the title compound as a white foam ( A-40). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.00 (t, J= 7.6 Hz, 3H), 1.34-1.59 (m, 3H), 1.60-1.77 (m, 3H), 1.94-2.03 (m, 1H), 2.10-2.18 (m, 2H), 2.27-2.41 (m, 2H), 2.53-2.67 (m, 1H), 2.94-2.97 (m, 3H), 3.06-3.19 (m, 1H), 3.71-3.82 (m, 1H), 3.82-3.96 (m, 1H), 6.61-6.68 (m, 1H), 6.92-7.00 (m, 1H), 7.29-7.37 (m, 2H), 7.43-7.49 (m, 1H), 8.22-8.32 (m, 1H). MS (ESI): [M + H] + = 439.2. Example 41 : (2-( Propionamide ) acetyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-41) Towards compounds To a solution of 5 (50 mg, 0.15 mmol), NaI (23 mg, 0.3 mmol) and 2-(propionamido)acetic acid (60 mg, 0.46 mmol) in acetone (1.8 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 3) to give 45 mg (69% yield) of the title compound as a white foam ( A-41). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.00 (t, J= 7.6 Hz, 3H), 1.62-1.78 (m, 3H), 1.97-2.04 (m, 1H), 2.15 (q, J= 7.6 Hz, 2H), 2.30-2.39 (m, 2H), 2.55-2.63 (m, 1H), 2.96 (s, 3H), 3.08-3.16 (m, 1H), 3.80-3.92 (m, 2H), 5.60-5.80 (m, 2H), 6.93-6.99 (m, 1H), 7.30-7.38 (m, 2H), 7.44-7.49 (m, 1H), 8.30 (t, J = 5.5 Hz, 1H). MS (ESI): [M + H] + = 425.4. Example 42 : (((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl L- Alanine (A-42) Towards compounds 5 (150 mg, 0.45 mmol), NaI (136 mg, 0.91 mmol) and N-(tert-Butoxycarbonyl)- N-methyl- To a solution of L-alanine (258 mg, 1.36 mmol) in acetone (5 mL) was added K 2CO 3 (314 mg, 2.27 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (10 mL) and washed with saturated NaHCO 3 aqueous solution (10 mL) and brine (10 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 200 mg (91% yield) of the compound as a white foam. 10. 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.19-1.28 (m, 3H) 1.28-1.46 (m, 9H), 1.57-1.79 (m, 3H), 1.93-2.02 (m, 1H), 2.28-2.42 (m, 2H), 2.54-2.62 (m, 1H), 2.96 (s, 3H), 3.07-3.19 (m, 1H), 3.97-4.08 (m, 1H), 5.60-5.84 (m, 2H), 6.92-7.05 (m, 1H), 7.29-7.37 (m, 2H), 7.37-7.44 (m, 1H), 7.44-7.51 (m, 1H). MS (ESI): [M + H] + = 483.3. Towards compounds To a solution of 10 (200 mg, 0.41 mmol) in DCM (15 mL) was added TFA (0.57 mL, 7.5 mmol). The reaction was stirred at 25°C for 16 h. The reaction was concentrated to give 250 mg of the title compound ( A-42). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.29-1.43 (m, 3H) 1.58-1.79 (m, 3H), 1.90-2.02 (m, 1H), 2.31-2.43 (m, 2H), 2.54-2.62 (m, 1H), 2.98 (s, 3H), 3.07-3.17 (m, 1H), 4.12-4.26 (m, 1H), 5.65-5.98 (m, 2H), 6.93-7.02 (m, 1H), 7.28-7.38 (m, 2H), 7.43-7.51 (m, 1H), 8.26-8.48 (m, 3H). MS (ESI): [M + H] + = 383.6. Example 43 : 1-(2-( Propionamide ) acetyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-43) Towards compounds To a solution of 2 (103 mg, 0.3 mmol), NaI (47 mg, 0.315 mmol) and 2-(2,2,2-trifluoroacetamido)-acetic acid (154 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 113 mg (79% yield) of the title compound as a white solid ( A-43). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.37-1.58 (m, 3H), 1.60-1.78 (m, 3H), 1.94-2.03 (m, 1H), 2.28-2.40 (m, 2H), 2.53-2.68 (m, 1H), 2.94-2.97 (m, 3H), 3.06-3.20 (m, 1H), 3.90-3.99 (m, 1H), 4.00-4.16 (m, 1H), 6.65-6.72 (m, 1H), 6.93-7.01 (m, 1H), 7.27-7.36 (m, 2H), 7.44-7.49 (m, 1H), 9.99 (t, J = 5.8 Hz, 1H). MS (ESI): [M + H] + = 479.1. Example 44 : (2-(2,2,2- trifluoroacetamido ) acetyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-44) Towards compounds To a solution of 5 (50 mg, 0.15 mmol), NaI (46 mg, 0.3 mmol) and 2-(2,2,2-trifluoroacetamido)-acetic acid (78 mg, 0.46 mmol) in acetone (4 mL) was added Et 3N (0.1 mL, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 7 / 3) to give 14 mg (20% yield) of the title compound as a white solid ( A-44). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.60-1.78 (m, 3H), 1.92-2.01 (m, 1H), 2.30-2.39 (m, 2H), 2.55-2.63 (m, 1H), 2.97 (s, 3H), 3.08-3.17 (m, 1H), 4.07 (t, J= 4.8 Hz, 2H), 5.64-5.86 (m, 2H), 6.93-6.99 (m, 1H), 7.30-7.36 (m, 2H), 7.44-7.49 (m, 1H), 10.04 (t, J = 5.4 Hz, 1H). MS (ESI): [M + H] + = 465.6. Example 45 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl dimethyl -L- Alanine (A-45) Towards compounds 2 (31 mg, 0.09 mmol), NaI (27 mg, 0.18 mmol) and ( To a solution of S)-2-(dimethylamino)-propionic acid (32 mg, 0.27 mmol) in acetone (1 mL) was added Et 3N (0.06 mL, 0.45 mmol). The reaction was heated to 70 °C for 20 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 3) to give 14 mg (37% yield) of the title compound as a yellow gum ( A-45). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.14 (d, J= 7.0 Hz, 3H), 1.37-1.58 (m, 3H), 1.60-1.77 (m, 3H), 1.95-2.03 (m, 1H), 2.14-2.26 (m, 6H), 2.28-2.36 (m, 2H), 2.56-2.70 (m, 1H), 2.94-2.97 (m, 3H), 3.05-3.19 (m, 1H), 3.20-3.28 (m, 1H), 6.62-6.70 (m, 1H), 6.93-7.02 (m, 1H), 7.26-7.36 (m, 2H), 7.44-7.49 (m, 1H). MS (ESI): [M + H] + = 425.5. Example 46 : (( S)-2-(2,2,2- trifluoroacetamido )-3- Methylbutyryloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-46) Towards compounds 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and ( To a solution of S)-2-(2,2,2-trifluoroacetamido)-3-methylbutanoic acid (97 mg, 0.45 mmol) in acetone (2 mL) was added Et 3N (0.11 mL, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 34 mg (44% yield) of the title compound as a white gum ( A-46). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.88-0.99 (m, 6H) 1.56-1.78 (m, 3H), 1.89-2.00 (m, 1H), 2.13-2.26 (m, 1H), 2.30-2.42 (m, 2H), 2.52-2.62 (m, 1H), 2.95 (s, 3H), 3.07-3.18 (m, 1H), 4.17-4.29 (m, 1H), 5.70-5.88 (m, 2H), 6.92-7.01 (m, 1H), 7.28-7.38 (m, 2H), 7.43-7.50 (m, 1H), 9.89 (d, J = 7.5 Hz, 1H). MS (ESI): [M + H] + = 507.5. Example 47 : 1-(2-(2,2,2- trifluoroacetamido ) acetyloxy ) Propyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-47) Towards compounds To a solution of 6 (50 mg, 0.14 mmol), NaI (22 mg, 0.15 mmol) and 2-(2,2,2-trifluoroacetamido)-acetic acid (72 mg, 0.42 mmol) in acetone (1.8 mL) was added Et 3N (0.1 mL, 0.7 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 28 mg (41% yield) of the title compound as a white foam ( A-47). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.80-1.02 (m, 3H), 1.58-1.92 (m, 5H), 1.93-2.04 (m, 1H), 2.27-2.41 (m, 2H), 2.53-2.70 (m, 1H), 2.95-2.98 (m, 3H), 3.04-3.20 (m, 1H), 3.92-4.02 (m, 1H), 4.03-4.16 (m, 1H), 6.57 (q, J= 5.6 Hz, 1H), 6.93-7.00 (m, 1H), 7.26-7.36 (m, 2H), 7.43-7.50 (m, 1H), 9.93-10.06 (m, 1H). MS (ESI): [M + H] + = 493.4. Example 48 : (( S)-2-(2,2,2- trifluoroacetamido ) propionyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-48) Towards compounds 5 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and ( To a solution of S)-2-(2,2,2-trifluoro-acetamido)propionic acid (84 mg, 0.45 mmol) in acetone (2 mL) was added Et 3N (0.11 mL, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 13 mg (18% yield) of the title compound as a white solid ( A-48). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.34-1.45 (m, 3H), 1.59-1.78 (m, 3H), 1.92-2.01 (m, 1H), 2.30-2.41 (m, 2H), 2.52-2.62 (m, 1H), 2.96 (s, 3H), 3.07-3.18 (m, 1H), 4.40-4.49 (m, 1H), 5.66-5.86 (m, 2H), 6.92-7.01 (m, 1H), 7.28-7.38 (m, 2H), 7.43-7.50 (m, 1H), 9.91-10.02 (m, 1H). MS (ESI): [M + H] + = 479.2. Example 49 : 1-(2-(2,2,2- trifluoroacetamido ) acetyloxy )-2- Methylpropyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-49) Towards compounds To a solution of 7 (93 mg, 0.25 mmol), NaI (39 mg, 0.26 mmol) and 2-(2,2,2-trifluoro-acetamido)acetic acid (128 mg, 0.75 mmol) in acetone (3 mL) was added Et 3N (0.17 mL, 1.25 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 51 mg (40% yield) of the title compound as a white foam ( A-49). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.80-1.08 (m, 6H), 1.60-1.78 (m, 3H), 1.93-2.15 (m, 2H), 2.28-2.41 (m, 2H), 2.64-2.72 (m, 1H), 2.96-2.99 (m, 3H), 3.03-3.21 (m, 1H), 3.92-4.03 (m, 1H), 4.03-4.18 (m, 1H), 6.45 (d, J= 4.9 Hz, 1H), 6.92-6.99 (m, 1H), 7.27-7.36 (m, 2H), 7.44-7.49 (m, 1H), 10.01 (br. s, 1H). MS (ESI): [M + H] + = 507.4. Example 50 : 1-(( S)-2-(2,2,2- trifluoroacetamido )-3- Methylbutyryloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-50) Towards compounds 2 (103 mg, 0.3 mmol), NaI (47 mg, 0.315 mmol) and ( To a solution of S)-2-(2,2,2-trifluoro-acetamido)-3-methylbutanoic acid (192 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 17 / 3) to give 128 mg (82% yield) of the title compound as a white foam ( A-50). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.82-0.99 (m, 6H), 1.38-1.55 (m, 3H), 1.56-1.78 (m, 3H), 1.91-2.00 (m, 1H), 2.10-2.20 (m, 1H), 2.26-2.39 (m, 2H), 2.58-2.69 (m, 1H), 2.94-2.97 (m, 3H), 3.05-3.16 (m, 1H), 4.12 (t, J = 7.6 Hz, 1H), 6.72 (q, J= 5.4 Hz, 1H), 6.91-7.01 (m, 1H), 7.27-7.36 (m, 2H), 7.43-7.48 (m, 1H), 9.76-9.88 (m, 1H). MS (ESI): [M + H] + = 521.5. Example 51 : 1-(( S)-2-(2,2,2- trifluoroacetamido ) propionyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-51) Towards compounds 2 (103 mg, 0.3 mmol), NaI (47 mg, 0.315 mmol) and ( To a solution of S)-2-(2,2,2-trifluoro-acetamido)propionic acid (167 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 81 mg (55% yield) of the title compound as a white foam ( A-51). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.32 (d, J= 7.3 Hz, 3H), 1.40-1.58 (m, 3H), 1.62-1.78 (m, 3H), 1.95-2.03 (m, 1H), 2.28-2.39 (m, 2H), 2.55-2.65 (m, 1H), 2.95-2.98 (m, 3H), 3.10-3.19 (m, 1H), 4.38-4.47 (m, 1H), 6.66 (q, J= 5.4 Hz, 1H), 6.91-7.00 (m, 1H), 7.28-7.36 (m, 2H), 7.44-7.50 (m, 1H), 9.90 (d, J = 6.9 Hz, 1H). MS (ESI): [M + H] + = 493.4. Example 52 : (4- Picoline -3- carbonyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-52) Towards compounds To a solution of 5 (100 mg, 0.3 mmol), NaI (90 mg, 0.6 mmol) and 4-methylpyridine-3-carboxylic acid (123 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 45 mg (35% yield) of the title compound ( A-52). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.62-1.77 (m, 3H), 1.92-2.00 (m, 1H), 2.31-2.40 (m, 2H), 2.55 (s, 3H), 2.58-2.66 (m, 1H), 3.00 (s, 3H), 3.08-3.16 (m, 1H), 5.80-6.12 (m, 2H), 6.98-7.02 (m, 1H), 7.22-7.27 (m, 1H), 7.28-7.34 (m, 1H), 7.41-7.44 (m, 1H), 7.45-7.48 (m, 1H), 8.64 (d, J = 5.0 Hz, 1H), 8.92 (s, 1H). MS (ESI): [M + H] + = 431.1. Example 53 : (2- Picoline -3- carbonyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-53) Towards compounds To a solution of 5 (100 mg, 0.3 mmol), NaI (90 mg, 0.6 mmol) and 2-methylpyridine-3-carboxylic acid (123 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 56 mg (43% yield) of the title compound as a white foam ( A-53). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.62-1.77 (m, 3H), 1.92-1.99 (m, 1H), 2.31-2.40 (m, 2H), 2.57-2.65 (m, 1H), 2.72 (s, 3H), 3.00 (s, 3H), 3.07-3.16 (m, 1H), 5.80-6.08 (m, 2H), 6.97-7.02 (m, 1H), 7.22-7.27 (m, 1H), 7.28-7.34 (m, 1H), 7.40-7.48 (m, 2H), 8.12-8.22 (m, 1H), 8.65-8.70 (m, 1H). MS (ESI): [M + H] + = 431.1. Example 54 : (6- Picoline -3- carbonyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-54) Towards compounds To a solution of 5 (100 mg, 0.3 mmol), NaI (90 mg, 0.6 mmol) and 6-methylpyridine-3-carboxylic acid (123 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (1 / 0 to 3 / 2) to give 44 mg (34% yield) of the title compound as a white foam ( A-54). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.61-1.76 (m, 3H), 1.92-1.99 (m, 1H), 2.30-2.40 (m, 2H), 2.55-2.63 (m, 1H), 2.58 (s, 3H), 2.99 (s, 3H), 3.05-3.15 (m, 1H), 5.82-6.08 (m, 2H), 6.96-7.01 (m, 1H), 7.21-7.27 (m, 1H), 7.28-7.34 (m, 1H), 7.42-7.49 (m, 2H), 8.12-8.24 (m, 1H), 8.97 (s, 1H). MS (ESI): [M + H] + = 431.1. Example 55 : 1-(( S)-2- acetamido -4- Methylpentyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-55) Towards compounds 2 (103 mg, 0.3 mmol), NaI (47 mg, 0.315 mmol) and ( To a solution of S)-2-acetamido-4-methylpentanoic acid (156 mg, 0.9 mmol) in acetone (4 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 11 / 9) to give 102 mg (71% yield) of the title compound as a white foam ( A-55). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.79-0.91 (m, 6H), 1.36-1.77 (m, 9H), 1.84 (s, 3H), 1.94-2.01 (m, 1H), 2.27-2.38 (m, 2H), 2.56-2.70 (m, 1H), 2.94-2.96 (m, 3H), 3.06-3.16 (m, 1H), 4.14-4.25 (m, 1H), 6.60-6.67 (m, 1H), 6.92-6.98 (m, 1H), 7.29-7.36 (m, 2H), 7.44-7.49 (m, 1H), 8.26 (d, J = 7.6 Hz, 1H). MS (ESI): [M + H] + = 481.1. Example 56 : (( S)-2- acetamido -4- Methylpentyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-56) Towards compounds 5 (100 mg, 0.3 mmol), NaI (90 mg, 0.6 mmol) and ( To a solution of S)-2-acetamido-4-methylpentanoic acid (156 mg, 0.9 mmol) in acetone (4 mL) was added K 2CO 3 (207 mg, 1.5 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 120 mg (86% yield) of the title compound as a white foam ( A-56). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.85 (d, J = 6.5 Hz, 3H), 0.89 (d, J= 6.6 Hz, 3H), 1.40-1.59 (m, 2H), 1.60-1.79 (m, 4H), 1.86 (s, 3H), 1.93-2.00 (m, 1H), 2.31-2.40 (m, 2H), 2.53-2.62 (m, 1H), 2.95 (s, 3H), 3.07-3.17 (m, 1H), 4.19-4.27 (m, 1H), 5.62-5.80 (m, 2H), 6.95-7.01 (m, 1H), 7.30-7.37 (m, 2H), 7.44-7.49 (m, 1H), 8.31 (d, J = 7.0 Hz, 1H). MS (ESI): [M + H] + = 467.2. Example 57 : 1-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl 2-(3- Methyloxetane -3- base ) Acetate (A-57) Towards compounds 2 (100 mg, 0.29 mmol), NaI (87 mg, 0.58 mmol) and (2 S,3 To a solution of R)-2-acetamido-3-methylpentanoic acid (151 mg, 0.87 mmol) in acetone (4 mL) was added Et 3N (0.163 mL, 1.17 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 3) to give 88 mg (63% yield) of the title compound ( A-57). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.65-0.78 (m, 2H), 0.78-0.89 (m, 4H), 1.12-1.21 (m, 1H), 1.28-1.59 (m, 4H), 1.62-1.78 (m, 4H), 1.87 (s, 3H), 1.92-2.03 (m, 1H), 2.28-2.39 (m, 2H), 2.55-2.65 (m, 1H), 2.91-2.99 (m, 3H), 3.04-3.20 (m, 1H), 4.08-4.25 (m, 1H), 6.62-6.74 (m, 1H), 6.90-7.01 (m, 1H), 7.27-7.38 (m, 2H), 7.42-7.51 (m, 1H), 8.09-8.22 (m, 1H). MS (ESI): [M + H] + = 481.2. Example 58 : ((2 S,3 R)-2- acetamido -3- Methylpentyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-58) Towards compounds 5 (100 mg, 0.30 mmol), NaI (91 mg, 0.60 mmol) and (2 S,3 To a solution of R)-2-acetamido-3-methylpentanoic acid (157 mg, 0.91 mmol) in acetone (4 mL) was added K 2CO 3 (209 mg, 1.51 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 130 mg (92% yield) of the title compound as a white solid ( A-58). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.79-0.92 (m, 6H), 1.17-1.28 (m, 1H), 1.37-1.49 (m, 1H), 1.56-1.81 (m, 4H), 1.88 (s, 3H), 1.92-2.02 (m, 1H), 2.30-2.41 (m, 2H), 2.53-2.62 (m, 1H), 2.95 (s, 3H), 3.07-3.19 (m, 1H), 4.14-4.24 (m, 1H), 5.64-5.83 (m, 2H), 6.92-7.00 (m, 1H), 7.28-7.38 (m, 2H), 7.43-7.51 (m, 1H), 8.19-8.29 (m, 1H). MS (ESI): [M + H] + = 467.2. Example 59 : ( S)-(((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl 2- Nicotinamide (A-59) Towards compounds To a solution of 5 (100 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and 2-aminopyridine-3-carboxylic acid (63 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 3) to give 40 mg (60% yield) of the title compound as a light yellow foam ( A-59). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.59-1.76 (m, 3H), 1.90-2.00 (m, 1H), 2.29-2.40 (m, 2H), 2.55-2.63 (m, 1H), 2.98 (s, 3H), 3.05-3.16 (m, 1H), 5.80-6.04 (m, 2H), 6.63-6.71 (m, 1H), 6.93-6.99 (m, 1H), 7.18-7.27 (m, 3H), 7.28-7.34 (m, 1H), 7.42-7.48 (m, 1H), 7.99-8.07 (m, 1H), 8.26 (dd, J = 1.9, 4.6 Hz, 1H). MS (ESI): [M + H] + = 432.0. Example 60 : 1-(2- acetamidoacetoxy ) Ethyl (R)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl - Methylcarbamate (A-60) At 0℃, RK Heming To a solution of 11 (1.0 g, 4.2 mmol) and DIPEA (1.36 g, 10.5 mmol) in DCM (42 mL) was slowly added 1-chloroethyl chloroformate (1.50 g, 10.5 mmol). The reaction was stirred at 25 °C for 1.5 h. The reaction was diluted with DCM (10 mL) and washed with water (20 mL) and brine (20 mL). The organic layer was precipitated with MgSO 4, dried, filtered and concentrated to give an oil. The oil was diluted with glacial MeOH and filtered to give 1.14 g (80% yield) of the compound as a white solid 12. 1 HNMR (600 MHz, CDCl 3) δ = 1.60-1.96 (m, 6H), 2.00-2.09 (m, 1H), 2.30-2.56 (m, 1H), 2.57-2.63 (m, 1H), 2.67-2.86 (m, 1H), 3.02-3.07 (m, 3H), 3.24-3.39 (m, 1H), 6.48-6.60 (m, 1H), 6.90-7.03 (m, 1H), 7.22-7.28 (m, 2H), 7.42-7.48 (m, 1H). Towards compounds To a solution of 12 (52 mg, 0.15 mmol), NaI (24 mg, 0.16 mmol) and acetylglycine (53 mg, 0.45 mmol) in acetone (1 mL) was added Et 3N (0.1 mL, 0.75 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (10 mL) and washed with saturated NaHCO 3 aqueous solution (10 mL) and brine (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (1 / 0 to 1 / 2) to give 39 mg (61% yield) of the title compound as a white foam ( A-60). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.36-1.56 (m, 3H), 1.60-1.78 (m, 3H), 1.86 (d, J= 3.0 Hz, 3H), 1.95-2.03 (m, 1H), 2.28-2.36 (m, 2H), 2.55-2.62 (m, 1H), 2.94-2.97 (m, 3H), 3.06-3.20 (m, 1H), 3.70-3.79 (m, 1H), 3.81-3.94 (m, 1H), 6.61-6.69 (m, 1H), 6.92-7.00 (m, 1H), 7.29-7.37 (m, 2H), 7.43-7.49 (m, 1H), 8.28-8.37 (m, 1H). MS (ESI): [M + H] + = 425.2. Example 61 : 1-(2-(3- Methyloxetane -3- base ) acetyloxy ) Ethyl (R)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-61) Towards compounds To a solution of 12 (121 mg, 0.35 mmol), NaI (105 mg, 0.7 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (137 mg, 1.05 mmol) in acetone (5 mL) was added K 2CO 3 (242 mg, 1.75 mmol). The reaction was heated to 70 °C for 4 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered, and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give a yellow oil. Diethyl ether (3 mL) was added, filtered, and the solid was washed with cold diethyl ether to give 15 mg (10% yield) of the title compound ( A-61). 1 HNMR (600 MHz, CD 3OD) δ = 1.38 (s, 3H), 1.41-1.64 (m, 3H), 1.72-1.88 (m, 3H), 2.04-2.10 (m, 1H), 2.32-2.39 (m, 1H), 2.43-2.51 (m, 1H), 2.66-2.72 (m, 1H), 2.73 (s, 2H), 3.05 (s, 3H), 3.32-3.34 (m, 1H), 4.34-4.39 (m, 2H), 4.57-4.64 (m, 2H), 6.68-6.75 (m, 1H), 7.01-7.15 (m, 1H), 7.27-7.34 (m, 2H), 7.44-7.48 (m, 1H). MS (ESI): [M + H] + = 438.2. Example 62 : 1-(( S)-2- Acetamidopropionyloxy ) Ethyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-62) Towards compounds 12 (52 mg, 0.15 mmol), NaI (24 mg, 0.16 mmol) and ( To a solution of S)-2-acetamidopropionic acid (59 mg, 0.45 mmol) in acetone (1 mL) was added Et 3N (0.1 mL, 0.75 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 47 mg (72% yield) of the title compound as a white foam ( A-62). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.15-1.30 (m, 3H), 1.34-1.58 (m, 3H), 1.60-1.77 (m, 3H), 1.84 (d, J= 14.2 Hz, 3H), 1.96-2.03 (m, 1H), 2.26-2.38 (m, 2H), 2.51-2.64 (m, 1H), 2.94-2.97 (m, 3H), 3.06-3.20 (m, 1H), 4.10-4.26 (m, 1H), 6.60-6.65 (m, 1H), 6.92-7.02 (m, 1H), 7.25-7.36 (m, 2H), 7.44-7.49 (m, 1H), 8.25-8.37 (m, 1H). MS (ESI): [M + H] + = 439.3. Example 63 : 1-(( S)-2- acetamido -3- Methylbutyryloxy ) Ethyl (R)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-63) Towards compounds 12 (52 mg, 0.15 mmol), NaI (24 mg, 0.16 mmol) and ( To a solution of S)-2-acetamido-3-methylbutanoic acid (72 mg, 0.45 mmol) in acetone (1 mL) was added Et 3N (0.1 mL, 0.75 mmol). The reaction was heated to 70 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 1) to give 49 mg (70% yield) of the title compound as a white foam ( A-63). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.82-0.93 (m, 6H), 1.36-1.56 (m, 3H), 1.60-1.77 (m, 3H), 1.88 (d, J= 21.0 Hz, 3H), 1.94-2.06 (m, 1H), 2.27-2.35 (m, 2H), 2.54-2.62 (m, 1H), 2.94-2.97 (m, 3H), 3.06-3.20 (m, 2H), 4.09-4.20 (m, 1H), 6.55-6.70 (m, 1H), 6.92-7.01 (m, 1H), 7.25-7.36 (m, 2H), 7.44-7.49 (m, 1H), 8.10-8.20 (m, 1H). MS (ESI): [M + H] + = 467.2. Example 64 : (2-(3- Methyloxetane -3- base ) acetyloxy ) methyl (R)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-64) Towards compounds To a solution of 13 (152 mg, 0.46 mmol), NaI (138 mg, 0.92 mmol) and 2-(3-methyloxetan-3-yl)acetic acid (120 mg, 0.92 mmol) in acetone (3 mL) was added K 2CO 3 (254 mg, 1.84 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 2) to give 74 mg (38% yield) of the title compound as a colorless oil ( A-64). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.32 (s, 3H), 1.60-1.79 (m, 3H), 1.92-2.02 (m, 1H), 2.30-2.41 (m, 2H), 2.53-2.62 (m, 1H), 2.76 (s, 2H), 2.95 (s, 3H), 3.07-3.15 (m, 1H), 4.23 (d, J = 5.8 Hz, 2H), 4.45 (d, J= 5.7 Hz, 2H), 5.62-5.74 (m, 2H), 6.94-6.99 (m, 1H), 7.29-7.36 (m, 2H), 7.45-7.50 (m, 1H). MS (ESI): [M + H] + = 424.2. Example 65 : ( Nicotine acyl group ) methyl (R)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-65) Towards To a solution of 13 (495 mg, 1.5 mmol), NaI (450 mg, 3.0 mmol) and nicotinic acid (554 mg, 4.5 mmol) in acetone (18 mL) was added Et 3N (1.05 mL, 7.5 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (3 / 2) to give 188 mg (30% yield) of the title compound ( A-65). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.60-1.77 (m, 3H), 1.90-2.00 (m, 1H), 2.30-2.40 (m, 2H), 2.56-2.65 (m, 1H), 2.99 (s, 3H), 3.06-3.15 (m, 1H), 5.88-6.08 (m, 2H), 6.97-7.02 (m, 1H), 7.21-7.26 (m, 1H), 7.27-7.33 (m, 1H), 7.42-7.47 (m, 1H), 7.60-7.65 (m, 1H), 8.28-8.35 (m, 1H), 8.86-8.90 (m, 1H), 9.07-9.13 (m, 1H). MS (ESI): [M + H] + = 417.2. Example 66 : (2- acetamidoacetoxy ) methyl 1-(2- Chlorophenyl )-2- Pendant cyclohexyl - Methylcarbamate (A-66) Towards To a solution of 13 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and 2-acetamidoacetic acid (53.2 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 17 mg (27% yield) of the title compound as a white foam ( A-66). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.62-1.77 (m, 3H), 1.87 (s, 3H), 1.94-2.04 (m, 1H), 2.29-2.41 (m, 2H), 2.55-2.65 (m, 1H), 2.96 (s, 3H), 3.06-3.18 (m, 1H), 3.79-3.93 (m, 2H), 5.62-5.79 (m, 2H), 6.93-7.01 (m, 1H), 7.29-7.39 (m, 2H), 7.43-7.50 (m, 1H), 8.38 (t, J = 5.8 Hz, 1H). MS (ESI): [M + H] + = 411.2. Example 67 : (( S)-2- acetamido -3- Methylbutyryloxy ) methyl 1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-67) Towards compounds 13 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and ( To a solution of S)-2-acetamido-3-methylbutanoic acid (72 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 1 / 4) to give 56 mg (82% yield) of the title compound as a white foam ( A-67). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.89-0.96 (m, 6H), 1.59-1.78 (m, 3H), 1.88 (s, 3H), 1.92-2.08 (m, 2H), 2.30-2.39 (m, 2H), 2.54-2.62 (m, 1H), 2.95 (s, 3H), 3.08-3.16 (m, 1H), 4.09-4.17 (m, 1H), 5.66-5.83 (m, 2H), 6.91-6.98 (m, 1H), 7.26-7.38 (m, 2H), 7.44-7.51 (m, 1H), 8.23 (d, J = 7.3 Hz, 1H). MS (ESI): [M + H] + = 453.2. Example 68 : (( S)-2- Acetamidopropionyloxy ) methyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-68) Towards 13 (50 mg, 0.15 mmol), NaI (46 mg, 0.30 mmol) and ( To a solution of S)-2-acetamidopropionic acid (60 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 13 / 7) to give 54 mg (84% yield) of the title compound as a white foam ( A-68). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 1.22-1.33 (m, 3H), 1.63-1.76 (m, 3H), 1.84 (s, 3H), 1.95-2.01 (m, 1H), 2.30-2.41 (m, 2H), 2.55-2.63 (m, 1H), 2.95 (s, 3H), 3.07-3.16 (m, 1H), 4.18-4.26 (m, 1H), 5.65-5.78 (m, 2H), 6.90-7.00 (m, 1H), 7.26-7.38 (m, 2H), 7.43-7.50 (m, 1H), 8.38 (d, J = 6.1 Hz, 1H). MS (ESI): [M + H] + = 425.2. Example 69 : (( S)-2- acetamido -4- Methylpentyloxy ) methyl (R)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-69) Towards compounds 13 (50 mg, 0.15 mmol), NaI (45 mg, 0.3 mmol) and ( To a solution of S)-2-acetamido-4-methylpentanoic acid (78 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (104 mg, 0.75 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 55 mg (79% yield) of the title compound as a white foam ( A-69). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 0.85 (d, J = 6.5 Hz, 3H), 0.90 (d, J= 6.5 Hz, 3H), 1.42-1.60 (m, 2H), 1.60-1.78 (m, 4H), 1.85 (s, 3H), 1.92-2.00 (m, 1H), 2.31-2.41 (m, 2H), 2.54-2.63 (m, 1H), 2.94 (s, 3H), 3.06-3.15 (m, 1H), 4.20-4.27 (m, 1H), 5.65-5.80 (m, 2H), 6.94-7.00 (m, 1H), 7.28-7.37 (m, 2H), 7.45-7.49 (m, 1H), 8.31 (d, J = 7.1 Hz, 1H). MS (ESI): [M + H] + = 467.2. Embodiment 70 : ((2 S,3 R)-2- acetamido -3- Methylpentyloxy ) methyl 1-(2- Chlorophenyl )-2- cyclohexyl methyl carbamate (A-70) Towards compounds 13 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol) and (2 S,3 To a solution of R)-2-acetamido-3-methylpentanoic acid (79 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 60 mg (85% yield) of the title compound as a white foam ( A-70). 1 HNMR (600 MHz, DMSO- d 6 ) δ = 0.81-0.92 (m, 6H), 1.18-1.26 (m, 1H), 1.38-1.49 (m, 1H), 1.59-1.81 (m, 4H), 1.87 (s, 3H), 1.93-2.01 (m, 1H), 2.30-2.40 (m, 2H), 2.54-2.62 (m, 1H), 2.95 (s, 3H), 3.08-3.16 (m, 1H), 4.14-4.20 (m, 1H), 5.66-5.82 (m, 2H), 6.93-6.98 (m, 1H), 7.29-7.37 (m, 2H), 7.45-7.50 (m, 1H), 8.26 (d, J = 7.2 Hz, 1H). MS (ESI): [M + H] + = 467.1. Example 71 : ( R)-(((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) methyl 2- Nicotinamide (A-71) To a solution of compound 13 (50 mg, 0.15 mmol), NaI (45 mg, 0.30 mmol), and 2-aminopyridine-3-carboxylic acid (63 mg, 0.45 mmol) in acetone (2 mL) was added K 2CO 3 (105 mg, 0.76 mmol). The reaction was heated to 70 °C for 1 h. The reaction was concentrated and redissolved in DCM (5 mL), washed with saturated NaHCO 3 aqueous solution (5 mL) and brine (5 mL). The organic layer was dried over MgSO 4, filtered, and concentrated to give an oil, which was purified by elution on a silica column with hexane / EA (100% hexane to 2 / 3) to give 42 mg (64% yield) of the title compound ( A-71) as a pale yellow foam. 1 HNMR(600 MHz, DMSO- d 6 ): 1.59 - 1.76 (m, 3H), 1.90 - 1.99 (m, 1H), 2.28 - 2.40 (m, 2H), 2.55 - 2.63 (m, 1H), 2.98 (s, 3H), 3.06 - 3.15 (m, 1H), 5.81 - 6.05 (m, 2H), 6.63 - 6.71 (m, 1H), 6.90 - 7.00 (m, 1H), 7.18 - 7.27 (m, 3H), 7.28 - 7.34 (m, 1H), 7.41 - 7.49 (m, 1H), 7.99 - 8.08 (m, 1H), 8.26 (dd, J = 1.9, 4.6 Hz, 1H). MS (ESI): [M + H] + = 432.1. Example 72 : (S)-2-((((9H- Fluorenyl -9- yl ) methoxy ) carbonyl ) Amine )-3-(4-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Phenyl ) Ethyl propionate (A-72) To a solution of diphosgene (237 mg, 1.2 mmol) in DCM (12 mL) was slowly added (((9 H-fluoren-9-yl)methoxy)carbonyl)- To a solution of ethyl L-tyrosine (863 mg, 2 mmol) in DCM (12 mL) was added a solution of DIPEA (1.05 mL, 6 mmol) in THF (24 mL) dropwise at 0°C over 30 min. The reaction was stirred at 0°C for 30 min, and then compound A solution of 1 (274 mg, 1 mmol) and DIPEA (0.18 mL, 1 mmol) in DCM (15 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (50 mL) and extracted with DCM (50 mL×2). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 590 mg (85% yield) of the compound as a white foam. 14. 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.12 (t, J= 6.0 Hz, 3H), 1.75 (m, 3H), 2.01 (m, 1H), 2.38-2.41 (m, 2H), 2.71 (m, 1H), 2.86-2.91 (m, 1H), 3.01-3.04 (m, 1H), 3.13 (s, 4H), 4.06 (q, J= 7.0 Hz, 2H), 4.16-4.27 (m, 4H), 7.04-7.14 (m, 3H), 7.25-7.42 (m, 8H), 7.47-7.49 (m, 1H), 7.64 (t, J= 8.0 Hz, 2H), 7.86-7.89 (m, 3H). MS (ESI): [M + H] + = 695.5. Towards compounds To a solution of 14 (150 mg, 0.22 mmol) in DCM (4.5 mL) was added piperidine (0.21 mL, 2.2 mmol). The reaction was stirred at 25 °C for 3 h. 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with DCM / MeOH (100% DCM to 97 / 3) to give 75 mg (74% yield) of the title compound as a yellow gum ( A-72). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.12 (t, J= 6.0 Hz, 3H), 1.73-1.77 (m, 3H), 2.02 (m, 1H), 2.39-2.42 (m, 2H), 2.73-2.85 (m, 3H), 3.13 (s, 4H), 3.51 (t, J = 6.5 Hz, 1H), 4.01 (q, J= 7.0 Hz, 2H), 7.02-7.19 (m, 5H), 7.33-7.41 (m, 2H), 7.48 (d, J = 7.5 Hz, 1H). MS (ESI): [M + H] + = 473.1. Example 73 : ( S)-2-(((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Ethyl acetate (A-73) To a solution of diphosgene (119 mg, 0.6 mmol) in DCM (6 mL) was slowly added a solution of 2-hydroxyethyl acetate (104 mg, 1 mmol) in DCM (6 mL) at 0°C, followed by the dropwise addition of a solution of DIPEA (0.52 mg, 3 mmol) in THF (6 mL) at 0°C over 30 min. The reaction was stirred at 0°C for 1 h, and then compound A solution of 1 (137 mg, 0.5 mmol) and DIPEA (0.087 mL, 0.5 mmol) in DCM (6 mL) was prepared. The reaction mixture was warmed to 25 °C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 1) to give 70 mg (38% yield) of the title compound as a white solid ( A-73). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.19 (t, J = 7.0 Hz, 3H), 1.68 (t, J= 11.0 Hz, 3H), 1.98-2.01 (m, 1H), 2.26-2.35 (m, 2H), 2.63-2.65 (m, 1H), 3.04 (s, 3H), 3.14-3.17 (m, 1H), 4.13 (q, J= 7.0 Hz, 2H), 4.66 (s, 2H), 7.02-7.05 (m, 1H), 7.30-7.33 (m, 2H), 7.45-7.47 (m, 1H). MS (ESI): [M + H] + = 368.3. Example 74 : ( S)-2-(((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Acetic acid (A-74) At 0°C, the compound ( To a solution of 4-[4-[(4-[(4-[(4-[(4-dimethylamino)-1-nitropropene-2-yl ... 2O (3 mL) and adjusted to pH = 3 with aqueous HCl (1 M), and then extracted with DCM (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give 50 mg (74% yield) of the title compound as a white foam ( A-74). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.68-1.72 (m, 3H), 1.98-2.02 (m, 1H), 2.24-2.33 (m, 2H), 2.60-2.64 (m, 1H), 3.04 (s, 3H), 3.16-3.21 (m, 1H), 4.55-4.90 (m, 2H), 7.07-7.09 (m, 1H), 7.27-7.33 (m, 2H), 7.44-7.46 (m, 1H). MS (ESI): [M + H] + = 340.2. Example 75 : (5- methyl -2- Pendant group -1,3- Two evil -4- base ) methyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )-( methyl ) Carbamate (A-75) To a solution of diphosgene (119 mg, 0.6 mmol) in DCM (6 mL) was slowly added a solution of 4-(hydroxymethyl)-5-methyl-1,3-dioxane-2-one (130 mg, 1 mmol) in DCM (6 mL) at 0°C, followed by the dropwise addition of a solution of DIPEA (0.52 mg, 3 mmol) in THF (6 mL) at 0°C over 30 min. The reaction was stirred at 0°C for 1 h, and then compound A solution of 1 (137 mg, 0.5 mmol) and DIPEA (0.087 mL, 0.5 mmol) in DCM (6 mL) was prepared. The reaction mixture was warmed to 25 °C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 45 mg (23% yield) of the title compound as a colorless oil ( A-75). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.66 (m, 3H), 2.09 (m, 1H), 2.16 (s, 3H), 2.34 (t, 2H), 2.56-2.59 (m, 1H), 2.97 (s, 3H), 3.12 (m, 1H), 4.96 (s, 2H), 6.95 (m, 1H), 7.29-7.33 (m, 2H), 7.45 (m, 1H). MS (ESI): [M + Na] + = 416.1. Example 76 : ( S)-2-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen )- Ethyl propionate (A-76) To a solution of diphosgene (89 mg, 0.45 mmol) in DCM (4.5 mL) was slowly added ( A solution of S)-ethyl 2-hydroxypropanoate (89 mg, 0.75 mmol) in DCM (4.5 mL) was then added dropwise at 0°C over 30 min to a solution of DIPEA (0.4 mL, 2.25 mmol) in THF (9 mL). The reaction was stirred at 0°C for 2 h, and then compound A solution of 1 (68 mg, 0.25 mmol) and DIPEA (0.044 mL, 0.25 mmol) in DCM (3.75 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 24 h. The reaction mixture was poured into H 2O (10 mL) and extracted with DCM (10 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 4 / 1) to give 18 mg (18% yield) of the title compound as a light yellow oil ( A-76). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.15-1.35 (m, 4H), 1.40-1.60 (m, 3H), 1.70-1.90 (m, 3H), 2.25-2.55 (m, 2H), 2.65-2.75 (m, 1H), 3.09 ( s, 3H), 3.18-3.32 (m, 1H), 4.16 (q, J = 7.1 Hz, 2H), 4.94 (q, J= 7.1 Hz, 1H), 7.05-7.15 (m, 1H), 7.21-7.31 (m, 2H), 7.40-7.50 (m, 1H). MS (ESI): [M + H] + = 382.2. Example 77 : (3- Methyloxetane -3- base ) methyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl )- Carbamate (A-77) To a solution of diphosgene (59 mg, 0.3 mmol) in DCM (3 mL) was slowly added a solution of (3-methyloxetan-3-yl)methanol (51 mg, 0.5 mmol) in DCM (3 mL) at 0°C, followed by the dropwise addition of a solution of DIPEA (0.26 mL, 1.5 mmol) in THF (6 mL) at 0°C over 30 min. The reaction was stirred at 0°C for 2 h, and then compound A solution of 1 (46 mg, 0.17 mmol) and DIPEA (0.029 mL, 0.17 mmol) in DCM (3 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 24 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 46 mg (76% yield) of the title compound as a light yellow oil ( A-77). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.04-1.24 (m, 3H), 1.58-1.79 (m, 3H), 1.92-2.05 (m, 1H), 2.26-2.37 (m, 2H), 2.55-2.68 (m, 1H), 3.01 (s, 3H), 3.08-3.18 (m, 1H), 4.02-4.47 (m, 6H), 6.88-6.98 (m, 1H), 7.25-7.36 (m, 2H), 7.42-7.50 (m, 1H). MS (ESI): [M + H] + = 366.1. Example 78 : 2-(((3- Methyloxetane -3- base ) methyl ) Sulfur ) Ethyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-78) To a solution of diphosgene (356 mg, 1.8 mmol) in DCM (18 mL) was slowly added a solution of 2-((3-methyloxetan-3-yl)methylthio)ethanol (486 mg, 3 mmol) in DCM (18 mL) at 0°C, followed by the dropwise addition of a solution of DIPEA (1.57 mL, 9 mmol) in THF (36 mL) at 0°C over 30 min. The reaction was stirred at 0°C for 2 h and then compound A solution of 1 (273 mg, 1.0 mmol) and DIPEA (0.175 mL, 1.0 mmol) in DCM (15 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 24 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 1) to give 238 mg (56% yield) of the title compound ( A-78). 1 HNMR (600 MHz, CD 3OD) δ = 1.36 (s, 3H), 1.73-1.90 (m, 3H), 2.04-2.12 (m, 1H), 2.33-2.41 (m, 1H), 2.42-2.50 (m, 1H), 2.71-2.99 (m, 5H), 3.09 (s, 3H), 3.32-3.38 (m, 1H), 4.20-4.37 (m, 4H), 4.45-4.52 (m, 2H), 7.04-7.09 (m, 1H), 7.26-7.32 (m, 2H), 7.43-7.48 (m, 1H). MS (ESI): [M + H] += 425.9. Example 79 : 2-(((3- Methyloxetane -3- base ) methyl ) Sulfonyl ) Ethyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-79) At 0°C, the compound ( To a solution of A-78) (33 mg, 0.08 mmol) in MeOH (0.3 mL) was added dropwise Oxone (96 mg, 0.16 mmol) in H 2O (0.3 mL) solution. The reaction was stirred at 25 °C for 16 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (1 / 2) to give 17 mg (47% yield) of the title compound as a white foam ( A-79). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.32 (s, 3H), 1.61-1.81 (m, 4H), 2.38-2.52 (m, 2H), 2.70-2.80 (m, 1H), 3.10 (s, 3H), 3.15-3.80 (m, 5H), 4.26 (s, 2H), 4.56-4.62 (m, 4H), 7.13-7.15 (m, 1H), 7.29-7.32 (m, 2H), 7.44-7.46 (m, 1H). MS (ESI): [M + H] + = 457.5. Example 80 : 2-(((3- Methyloxetane -3- base ) methyl ) sulfinyl group ) Ethyl (( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-80) At 0°C, the compound ( A-78) (85 mg, 0.2 mmol) in MeOH (0.8 mL) was added dropwise with NaIO 4 (43 mg, 0.2 mmol) of H 2O (0.4 mL) solution. The reaction was stirred at 25 °C for 3 h. The reaction was concentrated and redissolved in DCM (5 mL) and washed with H 2O (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with DCM / MeOH (100% DCM to 97 / 3) to give 79 mg (89% yield) of the compound as a white foam ( A-80). 1 HNMR (600 MHz, CD 3OD) δ = 1.48-1.62 (m, 3H), 1.71-1.91 (m, 3H), 2.03-2.11 (m, 1H), 2.33--2.52 (m, 2H), 2.71-2.83 (m, 1H), 2.88-3.29 (m, 3H), 3.09 (s, 3H), 3.30-3.38 (m, 2H), 4.33-4.58 (m, 4H), 4.59-4.67 (m, 1H), 4.71-4.81 (m, 1H), 7.02-7.10 (m, 1H), 7.26-7.34 (m, 2H), 7.43-7.49 (m, 1H). MS (ESI): [M + H] + = 442.0. Example 81 : ( S)-2-(((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) Oxygen ) Propionic acid (A-81) At 0°C, the compound ( A solution of 4-[ ... 2O (3 mL) and adjusted to pH = 3 with aqueous HCl (1 M), and then extracted with DCM (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give 16 mg (37% yield) of the title compound as a white solid ( A-81). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.43-1.59 (m, 3H), 1.70-1.86 (m, 4H), 2.28-2.35 (m, 1H), 2.45-2.53 (m, 1H), 2.65-2.85 (m, 1H), 3.10 (s, 3H), 3.20-3.28 (m, 1H), 4.95 (q, J= 6.9 Hz, 1H), 7.09-7.18 (m, 1H), 7.24-7.34 (m, 2H), 7.39-7.48 (m, 1H). MS (ESI): [M + H] + = 354.4. Example 82 : 3- Hydroxyl -2-( Hydroxymethyl )-2- Methylpropyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-82) To a solution of diphosgene (267 mg, 1.35 mmol) in DCM (13.5 mL) was slowly added a solution of (2,2,5-trimethyl-1,3-dioxane-5-yl)methanol (361 mg, 2.25 mmol) in DCM (13.5 mL) at 0°C, followed by the dropwise addition of a solution of DIPEA (1.18 mL, 6.75 mmol) in THF (27 mL) at 0°C over 30 min. The reaction was stirred at 0°C for 2 h, and then compound A solution of 1 (206 mg, 0.75 mmol) and DIPEA (0.131 mL, 0.75 mmol) in DCM (11 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (9 / 1) to give 141 mg (44% yield) of the compound as a white foam. 15. 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.29 (s, 6H), 1.36 (s, 3H), 1.72-1.86 (m, 3H), 2.34-2.46 (m, 2H), 2.67-2.76 (m, 1H), 3.10 (s, 3H), 3.20-3.34 (m, 1H), 3.40-3.80 (m, 5H), 4.01-4.24 (m, 2H), 6.98-7.08 (m, 1H), 7.26-7.33 (m, 2H), 7.41-7.47 (m, 1H). MS (ESI): [M + H] + = 424.3. Towards compounds To a solution of 15 (140 mg, 0.33 mmol) in MeOH (28 mL) was added HCl solution (0.42 mL, 0.2 M in EA). The reaction was stirred at 25 °C for 2 h. The reaction was concentrated and then purified on a silica gel column eluting with hexane / EA (1 / 1) to give 116 mg (92% yield) of the title compound ( A-82). 1 HNMR (500 MHz, acetone- d 6 ) δ = 0.86 (s, 3H), 1.70-1.90 (m, 3H), 2.35-2.50 (m, 2H), 2.65-2.80 (m, 1H), 3.09 (s, 3H), 3.25-3.85 (m, 6H), 4.00-4.20 (m, 2H), 7.05-7.15 (m, 1H), 7.25-7.40 (m, 2H), 7.42-7.52 (m, 1H). MS (ESI): [M + H] + = 384.3. Example 83 : ((2 R,3 S,4 S,5 R,6 R)-3,4,5,6- Tetrahydroxytetrahydro -2 H- Pyran -2- base ) methyl (( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-83) To a solution of diphosgene (267 mg, 1.35 mmol) in DCM (13.5 mL) was slowly added 1,2,3,4-tetra- A solution of O-acetyl-β-D-glucopyranose (361 mg, 2.25 mmol) in DCM (13.5 mL) was then added dropwise at 0°C over 30 min to a solution of DIPEA (1.18 mL, 6.75 mmol) in THF (27 mL). The reaction was stirred at 0°C for 2 h, and then compound A solution of 1 (206 mg, 0.75 mmol) and DIPEA (0.131 mL, 0.75 mmol) in DCM (11 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4. Dry, filter and concentrate to give a crude oil 16, which was directly used in the following reaction. At 25°C, the compound To a solution of 16 in MeOH (40 mL) was added 3% NaOMe (0.9 mL in MeOH). The reaction was stirred at 25°C for 2 h and then adjusted to pH 3 using Dowex® 50WX4 Hydrogen Form. The mixture was filtered and concentrated to give an oil, which was purified on a silica gel column using DCM / MeOH (100% DCM to 9 / 1) to give 40 mg (12% yield) of the title compound ( A-83). 1 HNMR (500 MHz, CD 3OD) δ = 1.73-1.91 (m, 3H), 2.02-2.15 (m, 1H), 2.31-2.48 (m, 2H), 2.70-2.81 (m, 1H), 3.09 (s, 3H), 3.14-3.19 (m, 0.6H), 3.36-3.43 (m, 2.4H), 3.44-3.52 (m, 0.4H), 3.63-3.73 (m, 0.6H), 3.88-4.02 (m, 0.6H), 4.17-4.28 (m, 1H), 4.42-4.54 (m, 1.4H), 4.56-4.66 (m, 0.4H), 5.08-5.16 (m, 0.6H), 7.00-7.08 (m, 1H), 7.24-7.36 (m, 2H), 7.42-7.48 (m, 1H). MS (ESI): [M + H] + = 444.4. Example 84 : 3- Hydroxyl -2-( Hydroxymethyl ) Propyl ( S)-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Carbamate (A-84) Towards compounds To a solution of 17 (1.0 g, 4.8 mmol) in acetone (25.5 mL) was added CH 3I (1.01 g, 71.1 mmol) and Ag 2O (1.16 g, 5.0 mmol). The suspension was stirred at 25°C for 16 h. The reaction was filtered through celite and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (100% hexane to 95 / 5) to give 965 mg (90% yield) of the compound as a white solid. 18. 1 HNMR (500 MHz, CDCl 3) δ = 3.10-3.20 (m, 1H), 3.72 (s, 3H), 4.01 (t, J = 11.5 Hz, 2H), 4.47 (dd, J= 4.8, 11.9 Hz, 2H), 5.44 (s, 1H), 7.30-7.45 (m, 3H), 7.46-7.55 (m, 2H). To CaCl To a solution of 2 (4.3 g, 39.2 mmol) in THF (110 mL) was added NaBH 4 (3.0 g, 78.3 mmol). The reaction was stirred at 25 °C for 4 h, and then compound 18 (965 mg, 4.35 mmol). The reaction was warmed to reflux and stirred for 16 h. The reaction was poured into ice water and extracted with DCM. The organic layer was washed with MgSO 4. Drying, filtration and evaporation gave 836 mg (99% yield) of the compound as a white solid. 19. 1 HNMR (500 MHz, acetone- d 6 ) δ = 2.15-2.30 (m, 1H), 3.40-3.50 (m, 2H), 3.65-3.80 (m, 2H), 4.24 (dd, J= 4.6, 11.6 Hz, 2H), 5.43 (s, 1H), 7.25-7.40 (m, 3H), 7.41-7.50 (m, 2H). To a solution of diphosgene (267 mg, 1.35 mmol) in DCM (13.5 mL) was slowly added A solution of 19 (437 mg, 2.25 mmol) in DCM (13.5 mL) was then added dropwise at 0°C over 30 min to a solution of DIPEA (1.18 mL, 6.75 mmol) in THF (27 mL). The reaction was stirred at 0°C for 2 h, and then compound A solution of 1 (206 mg, 0.75 mmol) and DIPEA (0.131 mL, 0.75 mmol) in DCM (11 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with DCM / EA (100% DCM to 10 / 1) to give 243 mg (71% yield) of the compound as a white foam. 20. 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.70-1.88 (m, 4H), 2.34-2.48 (m, 3H), 2.68-2.78 (m, 1H), 3.10 (s, 3H), 3.23-3.34 (m, 1H), 3.60-3.84 (m, 2H), 3.90-4.08 (m, 2H), 4.10-4.32 (m, 2H), 5.43 (s, 1H), 7.02-7.10 (m, 1H), 7.27-7.39 (m, 5H), 7.40-7.50 (m, 3H). MS (ESI): [M + H] + = 457.9. Towards compounds To a solution of 20 (100 mg, 0.22 mmol) in EA (10 mL) was added Pd(OH) 2 / C (15 mg). The reaction was carried out at 25 °C, H 2 atmosphere for 30 min. The reaction was filtered through a pad of celite and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (100% hexane to EA) to give 70 mg (86% yield) of the title compound ( A-84). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.68-1.87 (m, 4H), 2.34-2.45 (m, 2H), 2.65-2.75 (m, 1H), 3.07 (s, 3H), 3.22-3.33 (m, 1H), 3.50-3.74 (m, 5H), 4.12-4.26 (m, 2H), 7.01-7.08 (m, 1H), 7.24-7.33 (m, 2H), 7.41-7.47 (m, 1H). MS (ESI): [M + H] + = 370.1. Example 85 : 3-( Methylamino ) Propyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-85) To a solution of diphosgene (89 mg, 0.45 mmol) in DCM (4.5 mL) was slowly added (9 A solution of 1H-fluoren-9-yl)methyl 3-hydroxypropylmethylcarbamate (234 mg, 0.75 mmol) in DCM (4.5 mL) was added dropwise at 0°C over 30 min to a solution of DIPEA (0.392 mL, 2.25 mmol) in THF (9.0 mL). The reaction was stirred at 0°C for 1 h, and then compound A solution of 1 (134 mg, 0.49 mmol) and DIPEA (0.044 mL, 0.25 mmol) in DCM (4.0 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (8 / 2) to give 80 mg (28% yield) of the compound as a white solid. twenty one. 1 HNMR (500 MHz, CDCl 3) δ = 1.23-1.29 (m, 2H), 1.68-1.78 (m, 2H), 1.78-1.94 (m, 2H), 1.98-2.09 (m, 1H), 2.27-2.39 (m, 1H), 2.48-2.60 (m, 1H), 2.61-2.90 (m, 4H), 2.97-3.12 (m, 3H), 3.16-3.45 (m, 2H), 3.86-4.15 (m, 2H), 4.16-4.54 (m, 3H), 7.15-7.24 (m, 2H), 7.28-7.51 (m, 6H), 7.51-7.64 (m, 2H), 7.70-7.80 (m, 2H). MS (ESI): [M + H] + = 575.3. Towards compounds To a solution of 21 (80 mg, 0.139 mmol) in DCM (5 mL) was added piperidine (1 mL). The reaction was stirred at 25°C for 1.5 h. The reaction was poured into aqueous HCl (20 mL, 1 M) and extracted with DCM (20 mL x 2). The organic layer was washed with saturated NaHCO 3 aqueous solution (20 mL) was extracted, and then the organic layer was washed with MgSO 4 was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 5) to give 28 mg (57% yield) of the title compound as a light yellow solid ( A-85). 1 HNMR (500 MHz, CD 3OD) δ = 1.70-1.98 (m, 5H), 2.01-2.12 (m, 1H), 2.30-2.40 (m, 3H), 2.41-2.50 (m, 2H), 2.52-2.67 (m, 2H), 2.69-2.81 (m, 1H), 3.08 (s, 3H), 3.25-3.40 (m, 1H), 4.05-4.25 (m, 2H), 6.95-7.03 (m, 1H), 7.22-7.38 (m, 2H), 7.41-7.51 (m, 1H). MS (ESI): [M + H] + = 353.1. Example 86 : 3- aminopropyl ( S)-1-(2- Chlorophenyl )-2- Pendant oxycyclohexylmethylcarbamate (A-86) To a solution of diphosgene (166 mg, 0.84 mmol) in DCM (9.0 mL) was slowly added (9 A solution of 1H-fluoren-9-yl)methyl 3-hydroxypropylcarbamate (414 mg, 1.39 mmol) in DCM (9 mL) was added dropwise at 0°C over 30 min to a solution of DIPEA (0.728 mL, 4.17 mmol) in THF (18 mL). The reaction was stirred at 0°C for 1 h, and then compound A solution of 1 (127 mg, 0.46 mmol) and DIPEA (0.081 mL, 0.46 mmol) in DCM (7.5 mL) was prepared. The reaction mixture was warmed to 25°C and stirred for 16 h. The reaction mixture was poured into H 2O (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (8 / 2) to give 74 mg (29% yield) of the compound as a white solid. twenty two. 1 HNMR (500 MHz, CD 3OD) δ = 1.67-1.93 (m, 6H), 1.97-2.09 (m, 3H), 2.30-2.49 (m, 2H), 3.06 (s, 3H), 4.06-4.15 (m, 2H), 4.18-4.24 (m, 1H), 4.29-4.45 (m, 2H), 4.56-4.67 (m, 2H), 6.98-7.35 (m, 5H), 7.35-7.48 (m, 3H), 7.59-7.69 (m, 2H), 7.75-7.84 (m, 2H). MS (ESI): [M + H] + = 561.2. Towards compounds To a solution of 22 (74 mg, 0.13 mmol) in DCM (3.0 mL) was added piperidine (1 mL). The reaction was stirred at 25°C for 1.5 h. The reaction was poured into aqueous HCl (20 mL, 1 M) and extracted with DCM (20 mL x 2). The organic layer was washed with saturated NaHCO 3 aqueous solution (20 mL), and then the organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 5) to give 30 mg (67% yield) of the title compound as a sticky solid ( A-86). 1 HNMR (500 MHz, CD 3OD) δ = 1.70-1.97 (m, 5H), 2.02-2.16 (m, 1H), 2.32-2.54 (m, 2H), 2.59-2.86 (m, 3H), 3.08 (s, 3H), 3.28-3.40 (m, 1H), 4.08-4.28 (m, 2H), 6.97-7.09 (m, 1H), 7.25-7.38 (m, 2H), 7.42-7.55 (m, 1H). MS (ESI): [M + H] + = 339.4. Example 87 : 3-( Methylamino ) Propyl ( S)-1-(2- Chlorophenyl )-2- Oxycyclohexylmethylcarbamate (A-87) At 0°C, the compound ( To a solution of A-85) (17 mg, 0.048 mmol) in MeOH (2.0 mL) were added acetic acid (0.011 mL, 0.193 mmol) and NaBH 3CN (6.0 mg, 0.096 mmol). The reaction was stirred at 0°C for 5 min, then formaldehyde (0.004 mL, 0.118 mmol) was added. The reaction was warmed to 25°C and stirred for 2 h. The reaction was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give 14 mg (79% yield) of the title compound as a white solid ( A-87). 1 HNMR (500 MHz, CDCl 3) δ = 1.70-1.82 (m, 4H), 1.84-1.93 (m, 1H), 2.02-2.09 (m, 1H), 2.18-2.38 (m, 9H), 2.49-2.59 (m, 1H), 2.66-2.76 (m, 1H), 3.05 (s, 3H), 3.27-3.38 (m, 1H), 4.08-4.20 (m, 2H), 6.89-6.97 (m, 1H), 7.19-7.25 (m, 2H), 7.42-7.47 (m, 1H). MS (ESI): [M + H] + = 367.4. Example 88 : ( S)-1-((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-1- Pendant propane -2- base Acetate (A-88) At 0°C, the compound To a solution of 1 (150 mg, 0.55 mmol) and DIPEA (0.36 mL, 2.2 mmol) in DCM (3.0 mL) was added dropwise ( S)-1-(Chlorocarbonyl)ethyl acetate (0.17 mL, 1.4 mmol). The mixture was warmed to 25°C and stirred for 3 h. The reaction was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (85 / 15) to give 138 mg (72% yield) of the title compound as a light yellow foam ( A-88). 1 HNMR (500 MHz, CD 3OD) δ = 1.56 (d, J= 6.7 Hz, 3H), 1.70-1.90 (m, 3H), 2.00-2.08 (m, 1H), 2.10 (s, 3H), 2.30-2.40 (m, 1H), 2.45-2.55 (m, 1H), 2.65-2.75 (m, 1H), 3.13 (s, 3H), 3.20-3.30 (m, 1H), 5.46 (q, J= 6.7 Hz, 1H), 7.00-7.05 (m, 1H), 7.25-7.35 (m, 2H), 7.40-7.50 (m, 1H). MS (ESI): [M + H] + = 351.9. Example 89 : ( S)-2-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-2- Pendant oxyethyl Acetate (A-89) At 0°C, the compound To a solution of 1 (150 mg, 0.55 mmol) and DIPEA (0.27 mL, 1.6 mmol) in DCM (3.0 mL) was added (chlorocarbonyl)methyl acetate (0.09 mL, 0.8 mmol) dropwise. The mixture was warmed to 25°C and stirred for 3 h. The reaction was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (85 / 15) to give 94 mg (51% yield) of the title compound ( A-89). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.09-1.21 (m, 1H), 1.46-1.72 (m, 4H), 1.77-1.91 (m, 2H), 2.08 (s, 3H), 2.70 (s, 3H), 2.94-3.16 (m, 1H), 5.16 (s, 1H), 5.47 (s, 1H), 7.11-7.25 (m, 1H), 7.27-7.40 (m, 2H), 7.41-7.48 (m, 1H). MS (ESI): [M + H] + = 338.1. Example 90 : ( S)- N-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )- N- Methylnicotinamide (A-90) At 0°C, the compound 1 (237 mg, 1 mmol) and Et Nicotine chloride hydrochloride (534 mg, 3 mmol) was added to a 3N solution (0.63 mL, 4.5 mmol) in DCM (6 mL). The mixture was warmed to 25°C and stirred for 3 h. The reaction was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 3 / 2) to give 274 mg (80% yield) of the title compound ( A-90). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.68-1.80 (m, 2H), 1.89-1.98 (m, 1H), 2.02-2.10 (m, 1H), 2.29-2.37 (m, 1H), 2.41-2.49 (m, 1H), 2.58-2.67 (m, 1H), 2.99 (s, 3H), 3.18-3.27 (m, 1H), 7.07-7.14 (m, 1H), 7.30-7.38 (m, 2H), 7.46-7.52 (m, 1H), 7.53-7.59 (m, 1H), 8.05-8.11 (m, 1H), 8.71-8.76 (m, 1H), 8.82-8.86 (m, 1H). MS (ESI): [M + H] + = 343.0. Example 91 : ( S)-3-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl )-1- Picoline -1- thiophene Iodide (A-91) Towards compound ( A-90) (103 mg, 0.3 mmol) of CH 3CN (3 mL) solution was added with CH 3I (0.09 mL, 1.5 mmol). The reaction was heated to 80 °C for 16 h, and the solvent was removed under vacuum. Diethyl ether (3 mL) was added, filtered, and the solid was washed with cold diethyl ether to give 111 mg (76% yield) of the title compound ( A-91). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.70-1.84 (m, 2H), 1.93-2.08 (m, 2H), 2.34-2.41 (m, 1H), 2.52-2.56 (m, 1H), 2.62-2.63 (m, 1H), 3.02 (s, 3H), 3.17-3.26 (m, 1H), 4.42 (s, 3H), 7.15-7.21 (m, 1H), 7.31-7.40 (m, 2H), 7.49-7.53 (m, 1H), 8.21-8.27 (m, 1H), 8.84 (d, J = 8.1 Hz, 1H), 9.09 (d, J = 6.1 Hz, 1H), 9.34 (s, 1H). MS (ESI): [M + H] + = 357.4. Example 92 : ( S)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Methyl hydroxybutyrate (A-92) At 0°C, the compound To a solution of 1 (150 mg, 0.55 mmol) and DIPEA (0.29 mL, 1.65 mmol) in DCM (3.0 mL) was added dropwise methyl 3-(chlorocarbonyl)propionate (0.1 mL, 0.825 mmol). The reaction mixture was warmed to 25°C and stirred for 2 h. The reaction mixture was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (3 / 1) to give 150 mg (78% yield) of the title compound as a white solid ( A-92). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.66-1.86 (m, 4H), 2.20-2.27 (m, 1H), 2.34-2.41 (m, 1H), 2.54-2.68 (m, 3H), 2.86-2.99 (m, 2H), 3.30 (s, 3H), 3.26-3.35 (m, 1H), 3.60 (s, 3H), 7.01-7.08 (m, 1H), 7.20-7.29 (m, 2H), 7.39-7.44 (m, 1H). MS (ESI): [M + H] + = 352.1. Example 93 : ( S)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Pentoxybutyric acid (A-93) At 0°C, the compound ( A solution of 1-[4-[(2 ... 2O (3 mL) and adjusted to pH = 3 with aqueous HCl (1 M), and then extracted with DCM (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give 83 mg (83% yield) of the title compound as a white solid ( A-93). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.63-1.83 (m, 4H), 2.16-2.22 (m, 1H), 2.30-2.38 (m, 1H), 2.52-2.67 (m, 3H), 2.84-2.94 (m, 2H), 3.16 (s, 3H), 3.24-3.33 (m, 1H), 7.01-7.06 (m, 1H), 7.16-7.25 (m, 2H), 7.36-7.40 (m, 1H). MS (ESI): [M + H] + = 338.3. Example 94 : ( S)-2-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-2- Pendant oxoethane -1- Ammonium chloride (A-94) Towards compounds To a solution of 1 (68 mg, 0.25 mmol), (tert-butoxycarbonyl)glycine (111 mg, 0.375 mmol) and HATU (114 mg, 0.3 mmol) in DCM (2 mL) was added DIPEA (0.13 mL, 0.75 mmol). The reaction mixture was microwaved at 70°C for 20 min. The reaction was diluted with DCM (5 mL) and quenched with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO The reaction mixture was dried, filtered, and concentrated to give an oil, which was purified on a silica gel column using hexane / EA (1 / 0 to 3 / 2) as eluent to give a white foam. The white foam was dissolved in EA (1.5 mL), and HCl (0.15 mL, 2N in EA) was added. The reaction was stirred at 25 ° C for 16 h, filtered, and the solid was washed with cold EA to give 35 mg (38% yield) of the title compound ( A-94). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.68 (m, 3H), 1.95 (m, 1H), 2.26 (d, J = 15 Hz, 1H), 2.35 (d, J= 15 Hz, 1H), 2.63 (m, 1H), 3.02 (s, 3H), 3.15 (m, 1H), 4.10 (m, 1H), 4.29 (m, 1H), 7.02-7.04 (m, 1H), 7.25-7.33 (m, 2H), 7.45-7.46 (m, 1H), 8.18 (s, 3H). MS (ESI): [MH 2O] + = 277.1. Example 95 : (S)-2- acetamido -N-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )- N- Methylacetamide (A-95) Towards compound ( A-94) (35 mg, 0.12 mmol) and Et To a 3N solution of acetyl chloride (0.033 mL, 0.24 mmol) in DCM (2 mL) was added acetyl chloride (0.013 mL, 0.18 mmol). The reaction was stirred at 25°C for 16 h. The reaction was diluted with DCM (3 mL) and quenched with H 2O (3 mL) and brine (3 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (100% hexane to 2 / 1) to give 20 mg (50% yield) of the title compound ( A-95). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.67 (m, 3H), 1.86 (s, 3H), 1.95 (m, 1H), 2.17 (d, J = 12.9 Hz, 1H), 2.28 (d, J= 13.2 Hz, 1H), 2.55 (m, 1H), 3.03 (s, 3H), 3.14 (m, 1H), 4.16-4.21 (m, 2H), 6.97 (m, 1H), 7.24-7.30 (m, 2H), 7.42 (m, 1H), 8.11 (m, 1H). MS (ESI): [M + H] + = 337.2. Example 96 : ( S)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Isopropyl hydroxybutyrate (A-96) Towards compounds To a solution of 1 (136 mg, 0.5 mmol), 3-(isopropoxycarbonyl)propionic acid (121 mg, 0.75 mmol) and HATU (228, 0.6 mmol) in DCM (4 mL) was added DIPEA (0.26 mL, 1.5 mmol). The reaction mixture was microwaved at 70 °C for 30 min. The reaction was diluted with DCM (10 mL) and quenched with H 2O (10 mL) and brine (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with DCM / EA (100% DCM to 9 / 1) to give 77 mg (40% yield) of the title compound as a colorless oil ( A-96). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.18 (d, J = 1.8 Hz, 3H), 1.19 (d, J= 1.8 Hz, 3H), 1.66-1.86 (m, 4H), 2.20-2.27 (m, 1H), 2.34-2.42 (m, 1H), 2.50-2.67 (m, 3H), 2.87-2.94 (m, 2H), 3.18 (s, 3H), 3.26-3.34 (m, 1H), 4.88-4.97 (m, 1H), 7.03-7.08 (m, 1H), 7.20-7.28 (m, 2H), 7.38-7.43 (m, 1H). MS (ESI): [M + H] + = 380.2. Example 97 : ( S)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Ethyl butyrate (A-97) Towards compounds To a solution of 1 (68 mg, 0.25 mmol), 3-(isopropoxycarbonyl)propionic acid (55.1 mg, 0.375 mmol) and HATU (114 mg, 0.3 mmol) in DCM (2 mL) was added DIPEA (0.13 mL, 0.75 mmol). The reaction mixture was microwaved at 70 °C for 30 min. The reaction was diluted with DCM (10 mL) and washed with H 2O (10 mL) and brine (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with DCM / EA (100% DCM to 9 / 1) to give 47 mg (51% yield) of the title compound as a light yellow foam ( A-97). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.20 (t, J= 7.1 Hz, 3H), 1.66-1.86 (m, 4H), 2.20-2.26 (m, 1H), 2.34-2.42 (m, 1H), 2.52-2.68 (m, 3H), 2.86-2.98 (m, 2H), 3.18 (s, 3H), 3.26-3.35 (m, 1H), 4.01-4.13 (m, 2H), 7.03-7.08 (m, 1H), 7.20-7.28 (m, 2H), 7.38-7.43 (m, 1H). MS (ESI): [M + H] + = 366.2. Example 98 : ( S)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Pendant oxybutane -1- Ammonium chloride (A-98) Towards compounds To a solution of 1 (137 mg, 0.5 mmol), (4-((tert-butoxycarbonyl)amino)butanoic acid (152 mg, 0.75 mmol) and HATU (228 mg, 0.6 mmol) in DCM (4 mL) was added DIPEA (0.26 mL, 1.5 mmol). The reaction mixture was microwaved at 70 °C for 20 min. The reaction was diluted with DCM (10 mL) and washed with H 2O (10 mL) and brine (10 mL). The organic layer was washed with MgSO The mixture was dried, filtered, and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (1 / 0 to 2 / 1) to give a white foam. The white foam was dissolved in diethyl ether (1.5 mL), and HCl (1.5 mL, 2N in diethyl ether) was added. The reaction was stirred at 25°C for 16 h, filtered, and the solid was washed with cold diethyl ether to give 69 mg (39% yield) of the title compound ( A-98). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.67 (m, 3H), 1.81 (m, 2H), 1.91 (m, 1H), 2.19 (d, J = 12.9 Hz, 1H), 2.26 (d, J= 13.9 Hz, 1H), 2.43 (m, 1H), 2.76-2.83 (m, 4H), 3.02 (s, 3H), 3.36 (m, 1H), 6.94 (m, 1H), 7.26-7.31 (m, 2H), 7.44 (m, 1H), 8.07 (s, 3H). MS (ESI): [M + H] + = 323.1. Example 99 : ( S)- N-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )-4-( dimethylamino )- N- Methylbutyramide (A-99) Towards compounds To a solution of 1 (68 mg, 0.25 mmol), 4-(dimethylamino)butyric acid hydrochloride (84 mg, 0.5 mmol) and HATU (190 mg, 0.5 mmol) in DCM (2 mL) was added DIPEA (0.22 mL, 1.25 mmol). The reaction mixture was microwaved at 70°C for 30 min. The reaction was diluted with DCM (5 mL) and quenched with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with DCM / EA (1 / 1) to give 13 mg (15% yield) of the title compound as a white solid ( A-99). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.70-1.83 (m, 4H), 2.29-2.36 (m, 1H), 2.39-2.47 (m, 1H), 2.57-2.66 (m, 1H), 2.94-3.08 (m, 3H), 3.13 (s, 6H), 3.16 (s, 3H), 3.21-3.33 (m, 2H), 3.39-3.48 (m, 2H), 7.05-7.10 (m, 1H), 7.21-7.33 (m, 2H), 7.42-7.48 (m, 1H). MS (ESI): [M + H] + = 350.9. Example 100 : ( S)-2-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) benzyl Isobutyrate (A-100) Towards compounds To a solution of 22 (304 mg, 2.0 mmol) in 1,4-dioxane (5 mL) was added isobutyric anhydride (0.497 mL, 3.0 mmol) and 1-methylimidazole (0.24 mL, 3.0 mmol). The reaction was stirred at 25 °C for 1 h, and the solvent was removed under vacuum. The residue was diluted with DCM (10 mL) and eluted with H 2O (10 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (8 / 2) to give 340 mg (77% yield) of the compound as a white solid. twenty three. 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.17-1.19 (d, J =7.0 Hz, 6H), 2.56-2.68 (m, 1H), 5.38-5.45 (m, 2H), 7.39-7.53 (m, 2H), 7.54-7.94 (m, 3H). MS (ESI): [M + Na] + = 245.0. Towards compounds To a solution of 23 (83 mg, 0.374 mmol) in DCM (2 mL) was added oxalyl chloride (0.043 mL, 0.498 mmol). The reaction was stirred at 25 °C for 4 h, and the solvent was removed under vacuum. The residue was dissolved in DCM (2 mL), and compound A solution of 1 (68 mg, 0.25 mmol) and DIPEA (0.065 mL, 0.375 mmol) in DCM (1 mL) was prepared. The reaction was stirred at 25 °C for 16 h. The reaction was diluted with DCM (10 mL) and quenched with H 2O (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (85 / 15) to give 30 mg (27% yield) of the title compound as a white solid ( A-100). 1 HNMR (500 MHz, CD 3OD) δ = 1.17 (dd, J =7.0, 4.3 Hz, 6H), 1.76-1.85 (m, 1H), 1.86-2.00 (m, 2H), 2.10-2.20 (m, 1H), 2.53-2.59 (m, 1H), 2.59-2.68 (m, 2H), 2.75-2.84 (m, 1H), 2.96 (s, 3H), 3.38-3.49 (m, 1H), 5.10-5.20 (m, 1H), 5.24-5.33 (m, 1H), 7.29-7.36 (m, 2H), 7.37-7.42 (m, 1H), 7.47-7.54 (m, 4H), 7.55-7.59 (m, 1H). MS (ESI): [M + H] + = 442.3. Example 101 : ( S)- N-(1-(2- Chlorophenyl )-2- Pendant cyclohexyl )- N- methyl -4-( Methylamino ) Butyramide (A-101) Towards compounds To a solution of 1 (68 mg, 0.25 mmol), 4-((tert-butoxycarbonyl)(methyl)amino)butanoic acid (81.4 mg, 0.375 mmol) and HATU (114 mg, 0.3 mmol) in DCM (2 mL) was added DIPEA (0.13 mL, 0.75 mmol). The reaction mixture was microwaved at 70 °C for 1 h. The reaction was diluted with DCM (10 mL) and washed with H 2O (10 mL) and brine (10 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 45 mg (41% yield) of the compound as a white solid. twenty four. 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.46 (s, 9H), 1.69-1.89 (m, 5H), 2.24-2.42 (m, 2H), 2.54-2.68 (m, 3H), 2.84 (s, 3H), 3.12 (s, 3H), 3.23-3.40 (m, 4H), 7.00-7.12 (m, 1H), 7.20-7.29 (m, 2H), 7.38-7.45 (m, 1H). MS (ESI): [M + H] + = 437.4. Towards compounds To a solution of 24 (45 mg, 0.1 mmol) in EA (3 mL) was added HCl (3 mL, 1 M in EA). The reaction was stirred at 25 °C for 16 h, filtered, and the solid was removed. The solid was poured into saturated NaHCO 3 aqueous solution (20 mL) and extracted with DCM (20 mL×2). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with DCM / EA (1 / 1) to give 14 mg (42% yield) of the title compound as a white solid ( A-101). 1 HNMR (500 MHz, CD 3OD) δ = 1.72-1.90 (m, 5H), 2.00-2.09 (m, 1H), 2.32-2.44 (m, 2H), 2.40 (s, 3H), 2.56-2.75 (m, 5H), 2.65-2.75 (m, 1H), 3.12 (s, 3H), 3.32-3.38 (m, 1H), 6.94-7.00 (m, 1H), 7.24-7.31 (m, 2H), 7.42-7.48 (m, 1H). MS (ESI): [M + H] + = 337.3. Example 102 : ( S)-2-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl ) benzyl Acetate (A-102) Towards compounds To a solution of 22 (304 mg, 2.0 mmol) in 1,4-dioxane (5 mL) were added acetic anhydride (0.28 mL, 3.0 mmol) and 1-methylimidazole (0.240 mL, 3.0 mmol). The reaction was stirred at 25 °C for 1 h, and the solvent was removed under vacuum. The reaction was diluted with DCM (10 mL) and eluted with H 2O (10 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (8 / 2) to give 100 mg (26% yield) of the compound as a white solid. 25. 1 HNMR (500 MHz, DMSO- d 6 ) δ = 2.10 (s, 3H), 5.42 (s, 2H), 7.39-7.45 (m, 1H), 7.45-7.52 (m, 1H), 7.53-7.59 (m, 1H), 7.85-7.92 (m, 1H). MS (ESI): [M + Na] + = 217.1. Towards compounds To a solution of 25 (73 mg, 0.375 mmol) in DCM (2 mL) was added oxalyl chloride (0.064 mL, 0.75 mmol). The reaction was stirred at 25 °C for 4 h, and the solvent was removed under vacuum. The residue was dissolved in DCM (2 mL), and compound A solution of 1 (68 mg, 0.25 mmol) and DIPEA (0.065 mL, 0.375 mmol) in DCM (1 mL) was prepared. The reaction was stirred at 25 °C for 16 h. The reaction was diluted with DCM (10 mL) and quenched with H 2O (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 22 mg (21% yield) of the title compound as a viscous oil ( A-102). 1 HNMR (500 MHz, CD 3OD) δ = 1.75-1.85 (m, 1H), 1.88-1.97 (m, 2H), 2.10 (s, 3H), 2.11-2.19 (m, 1H), 2.52-2.58 (m, 1H), 2.60-2.70 (m, 1H), 2.75-2.84 (m, 1H), 2.95 (s, 3H), 3.37-3.49 (m, 1H), 5.11-5.20 (m, 1H), 5.23-5.32 (m, 1H), 7.32-7.35 (m, 2H), 7.37-7.40 (m, 1H), 7.48-7.54 (m, 4H), 7.55-7.59 (m, 1H). MS (ESI): [M + H] + = 414.3. Example 103 : ( S, E)-2-(3-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-3- Pendant oxypropyl -1- ene -1- base ) Phenyl Isobutyrate (A-103) Towards compounds 1(170 mg, 0.62 mmol), ( To a solution of E)-3-(2-(isobutyloxy)phenyl)acrylic acid (219 mg, 0.9 mmol) and HATU (285 mg, 0.75 mmol) in DCM (5 mL) was added DIPEA (0.33 mL, 1.9 mmol). The reaction was heated to 40 °C for 3 h. The reaction was diluted with DCM (5 mL) and quenched with H 2O (5 mL) and brine (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (3 / 1) to give 28 mg (10% yield) of the title compound ( A-103). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.30 (d, J = 1.2 Hz, 3H), 1.32 (d, J= 1.2 Hz, 3H), 1.72-1.90 (m, 4H), 2.29-2.37 (m, 1H), 2.44-2.50 (m, 1H), 2.52-2.65 (m, 1H), 2.88-2.97 (m, 1H), 3.31 (s, 3H), 3.32-3.38 (m, 1H), 7.03-7.09 (m, 1H), 7.17 (d, J= 8.1 Hz, 1H), 7.23-7.30 (m, 2H), 7.31-7.38 (m, 2H), 7.42-7.49 (m, 2H) 7.69 (d, J = 15.6 Hz, 1H), 7.94 (d, J = 7.7 Hz, 1H). MS (ESI): [M + H] + = 454.1. Example 104 : ( S, E)-2-(3-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-3- Pendant oxypropyl -1- ene -1- base ) Phenyl Acetate (A-104) Towards compounds To a solution of 26 (51.5 mg, 0.25 mmol) in DCM (2 mL) was added oxalyl chloride (0.043 mL, 0.5 mmol). The reaction was stirred at 25 °C for 4 h, and the solvent was removed under vacuum. The residue was dissolved in DCM (2 mL), and compound A solution of 1 (68 mg, 0.25 mmol) and DIPEA (0.065 mL, 0.375 mmol) in DCM (1 mL) was prepared. The reaction was stirred at 25 °C for 16 h. The reaction was diluted with DCM (10 mL) and quenched with H 2O (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 38 mg (36% yield) of the title compound as a white solid ( A-104). 1 HNMR (500 MHz, CDCl 3) δ = 1.71-1.80 (m, 2H), 1.82-1.94 (m, 1H), 2.00-2.12 (m, 1H), 2.35 (s, 3H), 2.44-2.51 (m, 1H), 2.52-2.60 (m, 1H), 2.62-2.73 (m, 1H), 3.18 (s, 3H), 3.30-3.41 (m, 1H), 6.90-7.05 (m, 2H), 7.10-7.18 (m, 1H), 7.22-7.32 (m, 3H), 7.38-7.43 (m, 1H), 7.44-7.50 (m, 1H), 7.66-7.76 (m, 1H), 7.80-7.87 (m, 1H). MS (ESI): [M + H] + = 426.1. Example 105 : (E)-N-((S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )-3-(2- Hydroxyphenyl )- N- Methacrylamide (A-105) At 0°C, the compound ( To a solution of 2-[ ... 2O (3 mL) and adjusted to pH = 3 with aqueous HCl (1 M), and then extracted with DCM (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil which was recrystallized from DCM and hexanes to give 12 mg (66% yield) of the title compound as a white solid ( A-105). 1 HNMR (500 MHz, acetone- d 6 ) δ = 1.71-1.90 (m, 4H), 2.29-2.36 (m, 1H), 2.44-2.50 (m, 1H), 2.57-2.66 (m, 1H), 3.28 (s, 3H), 3.31-3.43 (m, 1H), 6.86-6.93 (m, 1H), 6.98 (d, J= 8.1 Hz, 1H), 7.04-7.09 (m, 1H), 7.21-7.30 (m, 3H), 7.32-7.39 (m, 1H), 7.40-7.47 (m, 1H) 7.68 (d, J = 7.7 Hz, 1H), 7.96 (d, J = 15.6 Hz, 1H). MS (ESI): [M + H] + = 384.1. Example 106 : ( S, Z)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Pendant oxadiazole -2- enoic acid (A-106) At 0°C, the compound To a solution of 1 (137 mg, 0.5 mmol) and furan-2,5-dione (392 mg, 4 mmol) in DCM (5 mL) was added Et 3N (0.21 mL, 1.5 mmol). The reaction was stirred at 25°C for 22 h. The mixture was diluted with DCM (5 mL) and washed with aqueous NaOH (20 mL, 1 M). The aqueous layer was adjusted to pH = 3 with aqueous HCl (1 M) and then extracted with DCM (20 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give 76 mg (45% yield) of the title compound as a light yellow solid ( A-106). 1 HNMR (500 MHz, CDCl 3) δ = 1.60-1.64 (m, 1H), 1.79-1.88 (m, 2H), 1.98-2.01 (m, 1H), 2.57-2.66 (m, 2H), 2.77-2.80 (m, 1H), 3.06 (s, 3H), 3.17-3.21 (m, 1H), 6.32-6.35 (m, 1H), 6.66-6.69 (m, 1H), 7.15-7.18 (m, 1H), 7.25-7.29 (m, 2H), 7.44-7.47 (m, 1H). MS (ESI): [M + Na] + = 358.0. Example 107 : ( S, Z)-4-((1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) Amine )-4- Pendant oxadiazole -2- enoic acid (A-107) Towards( To a solution of E)-4-ethoxy-4-oxobut-2-enoic acid (216 mg, 1.5 mmol) in DCM (5 mL) was added oxalyl chloride (0.26 mL, 3 mmol) and a few drops of DMF. The mixture was stirred at 25°C for 1 hour and then dried under vacuum. The residue was dissolved in DCM (3 mL) and compound 1 was added at 0°C. A solution of 1 (137 mg, 0.5 mmol) and DIPEA (0.26 mL, 1.5 mmol) in DCM (3 mL) was prepared. The reaction was stirred at 25 °C for 2 h. The mixture was diluted with DCM (5 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was purified by MgSO 4, dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (4 / 1) to give 76 mg (40% yield) of the title compound as a light yellow foam ( A-107). 1 HNMR (500 MHz, CD 3OD) δ = 1.32 (t, J= 12.0 Hz, 3H), 1.76-1.84 (m, 3H), 2.03-2.06 (m, 1H), 2.43-2.46 (m, 2H), 2.62-2.65 (m, 1H), 3.18 (s, 3H), 3.31-2.34 (m, 1H), 4.27 (q, J= 12.0 Hz, 2H), 6.67-6.70 (m, 1H), 7.03-7.05 (m, 1H), 7.27-7.31 (m, 2H), 7.46-7.48 (m, 1H), 7.54-7.57 (m, 1H). MS (ESI): [M + H] + = 364.1. Example 108 : ((( S)-1-(2- Chlorophenyl )-2- Pendant cyclohexyl )( methyl ) aminoformyl )- L- Alanyl -L- Proline (A-108) Towards compounds A solution of 27 (1.3 g, 9.08 mmol) in DCM (25 mL) was added dropwise to (tert-butoxycarbonyl)- A solution of L-alanine (2.06 g, 10.9 mmol), HOBT (2.21 g, 16.3 mmol), EDCI (3.13 g, 16.3 mmol), and DIPEA (5.69 mL, 32.7 mmol) in DCM (25 mL) was stirred at 25 °C for 4 h. The reaction was diluted with DCM (100 mL) and quenched with H 2O (25 mL). The organic layer was separated and washed with aqueous HCl (1 M) and then with saturated NaHCO 3 aqueous solution (20 mL) and brine (20 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (7 / 3) to give 1.71 g (60% yield) of the compound as a viscous oil 28. 1 HNMR (500 MHz, CDCl 3) δ = 1.25 (t, J = 7.1 Hz, 3H), 1.35 (d, J= 6.9 Hz, 3H), 1.42 (s, 9H), 1.86-2.12 (m, 3H), 2.16-2.29 (m, 1H), 3.55-3.64 (m, 1H), 3.65-3.76 (m, 1H), 4.08-4.24 (m, 2H), 4.37-4.57 (m, 2H). MS (ESI): [M + H] + = 315.3. Towards compounds To a solution of 28 (527 mg, 1.67 mmol) in DCM (10 mL) was added TFA (5.0 mL). The reaction was stirred at 25 °C for 16 h and then concentrated. The reaction was diluted with DCM (10 mL) and quenched with H 2O (5 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give a viscous oil (360 mg), which was dissolved in DCM (8 mL) and saturated NaHCO 3 aqueous solution (12 mL). Diphosgene (166 mg, 0.84 mmol) was slowly added to the solution at 0°C. The mixture was stirred at 25°C for 5 h. The reaction was diluted with DCM (10 mL) and quenched with H 2O (5 mL). The organic layer was washed with MgSO 4Dry, filter and concentrate to obtain the compound as a viscous oil 29 (373 mg). Towards compounds To a solution of 29 (373 mg, 1.55 mmol) in DCM (10 mL) was added compound 1 (118 mg, 0.43 mmol) and Et 3N (0.301 mL, 2.16 mmol). The reaction was heated to 70 °C overnight. The reaction was diluted with DCM (10 mL) and washed with H 2O (5 mL). The organic layer was washed with MgSO The precipitate was dried, filtered and concentrated to give an oil which was purified on a silica gel column eluting with hexane / EA (6 / 4) to give 192 mg (94% yield) of the compound as a white solid. 30. 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.07-1.21 (m, 4H), 1.23-1.33 (m, 1H), 1.37-1.56 (m, 5H), 1.56-1.71 (m, 3H), 1.73-2.06 (m, 6H), 2.07-2.22 (m, 1H), 2.82-3.06 (m, 1H), 3.49-3.63 (m, 1H), 3.64-3.77 (m, 1H), 3.95-4.13 (m, 2H), 4.19-4.31 (m, 1H), 4.76-4.89 (m, 1H), 6.12-6.25 (m, 1H), 7.22-7.48 (m, 4H). MS (ESI): [M + Na] + = 500.3. Towards compounds To a solution of 30 (187 mg, 0.39 mmol) in THF (4 mL) was added aqueous LiOH (2 mL, 1 M). The reaction was stirred at 25 °C for 1 h and then concentrated. The reaction was diluted with DCM (10 mL) and washed with pH 3 HCl solution (10 mL). The organic layer was washed with MgSO 4, dried, filtered and concentrated to give an oil, which was purified on a silica gel column eluting with hexane / EA (1 / 1) to give 110 mg (63% yield) of the title compound ( A-108). 1 HNMR (500 MHz, DMSO- d 6 ) δ = 1.32 (d, J= 6.9 Hz, 4H), 1.35-1.52 (m, 3H), 1.55-1.64 (m, 1H), 1.77-1.99 (m, 4H), 2.03-2.23 (m, 2H), 2.61 (s, 3H), 3.39-3.46 (m, 1H), 3.50-3.58 (m, 1H), 4.23 (dd, J = 3.9, 8.7 Hz, 1H), 4.91 (q, J= 6.9, 13.9 Hz, 1H), 5.08 (dd, J= 3.2, 6.8 Hz, 1H), 7.33-7.38 (m, 2H), 7.42-7.48 (m, 1H), 7.49-7.54 (m, 1H). MS (ESI): [M + Na] + = 472.2. Example 109 : Metabolic stability test of test compounds Mouse, rat, dog, monkey, and human liver S9 Fraction metabolic stability test The protocol for metabolic stability studies of the mouse, rat, dog, monkey and human liver S9 fractions was used to determine the half-life (T 1 / 2 ) and its in vitro conversion from prodrug to SK's release efficiency of his life. The following is a summary of the S9 study: 1) For the SK-1 statin release efficiency assay, pooled liver S9 fractions (mouse, rat, dog, monkey, or human) were obtained from commercial suppliers (e.g., CD-1 male mouse liver S9, SD male rat liver S9, Beagle male dog liver S9, and mixed-sex pooled human liver S9 were purchased from Corning (Woburn, MA, USA); Malayan male monkey liver S9 was purchased from Gibco (Thermo Fisher Scientific Inc. USA)) and stored at −80°C until use. 2) The 1% MgCl2 solution was added to the 1% MgCl2 solution. 2) Preincubate the test substance (3 μM, final acetonitrile concentration 0.1%) with potassium phosphate buffer (100 mM, pH 7.4) (triplicate) in a 37°C incubator for 10 min. 3) Initiate the reaction by adding preheated S9 fraction (1.0 mg / mL) in the presence of 2 mM NADPH. The final incubation mixture volume is 200 μL. 4) Terminate all reactions at predefined time points (0 to 60 min) using five volumes of extraction solvent. 5) Centrifuge aliquots of the terminated incubation mixture at 20,000 x g for 5 min. 6) Analyze the remaining amount of test substance and the amount of supernatant by LC-MS / MS. The data are shown in Table 1 below. In vitro analysis using liver S9 fractions from mice, rats, dogs, monkeys, and humans The release efficiency test of SK-Tamiflu showed that the prodrug compound can be converted into SK-1amin has variable release efficiencies, indicating that it is converted into SK his life. Whole blood metabolic stability studies in mice, rats, dogs, monkeys, and humans The protocol for the whole blood metabolic stability test in mice, rats, dogs, monkeys and humans was used to determine the in vitro conversion of the disclosed compounds from prodrugs to SK's release efficiency of his life. The following is a summary of the whole blood study: 1) For the SK-Tamiflu release efficiency assay, mixed-sex whole blood from rats was obtained from commercial suppliers (e.g., heparinized CD-1 mouse whole blood pool (N>5) and SD rat whole blood pool (N>5) were purchased from BioLASCO (Yi-Lan, Taiwan); heparinized beagle dog whole blood pool (N=3) was purchased from the Center for Toxicology and Preclinical Sciences (CTPS, QPS, Taiwan); heparinized Malay macaque whole blood pool (N=3) was purchased from the Laboratory Animal Center (LAC) of the National Defense Medical Center (NDMC); and fresh heparinized human whole blood was obtained from healthy donors (N>6)) and stored at 4°C until use. 2) The test substance was incubated in prewarmed rat whole blood at 37°C at 3 μM (final acetonitrile concentration 1%) for up to 60 min. 3) At predefined time points (0 to 60 min) after incubation, 100 μL aliquots of the spiked sample solution were removed and immediately extracted by adding 5 volumes of extraction solvent, followed by centrifugation at 20,000 x g for 5 min. 4) The remaining amount of test compound and the amount of ketamine formed in the supernatant fraction were analyzed by LC-MS / MS. The measurement results were then used to calculate the conversion of the test compound to The conversion efficiency of SK-α is shown in Table 2 below. In vitro SK-Tagmin release efficiency studies using whole blood from mice, rats, dogs, monkeys, and humans showed that the prodrug compound could be converted into SK-1amin has variable release efficiencies, indicating that it is converted into SK his life. Example 110 : Pharmacokinetic studies In CD-1 mice and SD rats, ( SK-etamine) or oral administration ( The pharmacokinetic profiles of the test articles in mice and rats were evaluated following administration of the SK-1 inhibitor (a statin or prodrug). For intravenous (IV) administration, blood samples were collected from the facial vein using heparinized tubes before and 3, 10, 30, 1, 2, 3, 4, 6, and 8 hours after dosing. For oral (PO) administration, blood samples were drawn from the facial vein using heparinized tubes before and 10, 30, 1, 2, 3, 4, 5, 6, and 8 hours after dosing. In the mouse PK study, mice were grouped to implement a sparse sampling strategy. Each mouse provided two blood samples at different collection times. Blood samples were collected from alternating groups of three mice at each time point. To prevent compound degradation, once drawn, blood samples were immediately mixed with acetonitrile (containing 0.1% formic acid) in a 1:3 (v / v) ratio. Deproteinized samples were temporarily stored on ice and then at -70°C prior to bioanalysis. The concentration of analytes in blood was determined by LC-MS / MS. TM WinNonlin ® The software calculates various pharmacokinetic parameters. In order to quantify the biotransformation efficiency of the test compound in the circulatory system, the The relative bioavailability of SK-1amin. The relative bioavailability value is expressed as the conversion of The AUC of SK-1tamin was determined by dose-adjusted intravenous administration alone. The data are shown in Tables 3 and 4 below. For canine pharmacokinetic studies, male Beagle dogs were housed individually. Dogs in the oral administration group were fasted overnight prior to use but had free access to water. Dogs in the IV group had free access to food and water. SK-Tamiflu HCl salt was administered intravenously (IV) to each dog at a single dose of 3.75 μmol / kg. The vehicle for SK-Tamiamine HCl salt is saline. For other test compounds, a single dose of each test compound was administered to each dog via oral gavage (n=3 / group). The dose of each test compound is listed in Table 5. Blood samples were collected at designated time points (before administration, 10 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h after administration) after administration of individual dogs in the IV and PO groups. In order to prevent compound degradation, once the blood sample was drawn, it was immediately mixed with acetonitrile (containing 0.1% formic acid) in a ratio of 1:3 (v / v). The deproteinized samples were temporarily stored in ice and then stored at -70°C before bioanalysis. The concentration of the analyte in the blood was determined by LC-MS / MS. Phoenix was used. TM WinNonlin ® The software calculates various pharmacokinetic parameters. To quantify the biotransformation efficiency of the test compound in the circulatory system, the The relative bioavailability of SK-Citric Acid is shown in Table 5 below. For the monkey pharmacokinetic study, three Malay macaques (two males and one female, cynomolgus monkeys) from the Laboratory Animal Center (LAC) of the National Defense Medical Center (NDMC) were studied. The average age of the subjects was 6 years and the average weight was 6.6 kg (range 6 to 7 kg). There was a washout period of at least 7 days between treatments. On the day of the in vivo experiment, the monkeys were sedated by intramuscular injection of Alfaxan (5 mg / kg) and Dexmedetomidine (10 mcg / kg). For intravenous administration, Sektamine HCl solution was administered slowly via the cephalic vein as a bolus injection at a dose of 33.2 μmol / kg. For oral administration, the dose of each test compound is listed in Table 6 and administered via oral gavage. Monkeys in the IV treatment group had free access to a laboratory diet, while monkeys in the oral treatment group fasted overnight before treatment and were fed 2 to 3 hours after test substance administration. Drinking water was available ad libitum during the study. Blood samples (0.35 mL / each) were collected from the monkeys via the saphenous vein. The collected blood samples were placed in tubes containing heparin as an anticoagulant. Blood samples were collected from the intravenous (IV) group before dosing and 10 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, and 8 h after dosing. For the PO group, blood samples were collected before dosing and 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, and 8 h after dosing. To prevent compound degradation, 100 μL of blood samples were immediately drawn from monkeys and mixed with 300 μL of acetonitrile (containing 0.1% formic acid) at a 1:3 (v / v) ratio. Deproteinized samples were temporarily stored on ice and then at -70°C prior to bioanalysis. Analyte concentrations in blood were determined by LC-MS / MS. Finally, it should be noted that there are other ways to implement the present invention. Therefore, the embodiments of the present invention will be described in terms of examples, but the present invention is not limited to what is described, and further modifications can be made within the scope of the present invention or equivalents added to the scope of the claims. All publications or patents cited herein are incorporated herein by reference. Throughout this specification, references to "an embodiment," "some embodiments," "an embodiment," "another embodiment," "an embodiment," "a specific embodiment," or "some embodiments" mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or embodiment is included in at least one embodiment or embodiment of the present disclosure. Thus, the appearance of phrases such as "in some embodiments," "in one embodiment," "in an embodiment," "in another embodiment," "in an embodiment," "in a specific embodiment," or "in some embodiments" in various places throughout this specification are not necessarily referring to the same embodiment or embodiment of the present disclosure. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or embodiments. Although illustrative implementations have been shown and described, those skilled in the art will understand that the above implementations should not be construed as limiting the disclosure, but rather that changes, substitutions, and modifications may be made to the implementations without departing from the spirit, principles, and scope of the disclosure.

Claims

1. A compound having the structure of formula A-12, A-16, A-27, A-52, or A-53; or a pharmaceutically acceptable salt of any of the aforementioned compounds.

2. A pharmaceutical composition comprising a compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof.

3. The pharmaceutical composition as claimed in claim 2, wherein the pharmaceutical composition is an oral preparation.

4. Use of a therapeutically effective amount of a compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as claimed in claim 2 or 3 for the manufacture of a medicament for the treatment of individual pain.

5. Use of a therapeutically effective amount of a compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as claimed in claim 2 or 3 for the manufacture of a medicament for the treatment of individual depression.

6. The use of a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of claim 2 or 3 for the manufacture of a medicament for treating an individual with a neurological disorder, mental disorder or central nervous system disease associated with NMDA receptor inhibition.

7. As requested in item 6, wherein the mental disorder is selected from: alcohol or drug use disorder, anxiety disorder, adult attention deficit / hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, opioid use disorder, post-traumatic stress disorder, schizophrenia, dissociative disorders, feeding and eating disorder, sexual and paraphilic disorder, sleep and wake disorder, childhood mental disorder, personality disorder, affective disorder, substance abuse disorder, and suicidal ideation.

8. The use of a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 2 or 3, for the manufacture of a medicament for treating an individual with a condition associated with NMDA receptor inhibition, wherein the condition is selected from the group consisting of: anxiety disorders, seasonal affective disorder, mania, bipolar disorder, obsessive-compulsive disorder, jet lag-related insomnia and fatigue, schizophrenia, seizures, panic attacks, depression, alcoholism, drug addiction, alcoholism, substance abuse, withdrawal symptoms, insomnia, psychotic disorders, epilepsy, sleep disorders, sleep apnea syndrome, mandatory eating disorder, fibromyalgia, stress, obesity, Parkinson's disease, cognitive impairment, memory disorders, premenstrual syndrome, migraine, memory loss, Alzheimer's disease, and / or asymptomatic diseases or disorders associated with normal or pathological aging.