Analogs of mannose-6-phosphate and uses of the same

Abstract

This application pertains to a compound of Formula (I), Formula (I'), Formula (I") or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein X, R1, R2, R3, R5, R6, and R7 are as defined herein, and uses of such compounds in methods of treating neurodegenerative diseases, neurodevelopmental disorders, and age-related memory impairment.

Description

Attorney Docket No.: 058636.00849ANALOGS OF MANNOSE-6-PHOSPHATE AND USES OF THE SAMECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of the filing of U. S. Provisional Application No. 63 / 720,042, filed on November 13, 2024, the contents of which is incorporated herein by reference in its entirety for all purposes.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with government support under grant numbers MH065635 awarded by the National Institutes of Health. The government has certain rights to this invention.TECHNICAL FIELD

[0003] This application relates to amidate phosphonate and amidate phosphate ester compounds and uses of the same in the treatment of neurodegenerative diseases, neurodevelopmental disorders, age-related cognitive impairment, and age-related memory impairment. This application also relates to phosphono and phospho diamidate compounds and uses of the same in the treatment of neurodegenerative diseases, neurodevelopmental disorders, age-related cognitive impairment, and age-related memory impairment. This application also relates to phosphonate ester and phosphate ester compounds and uses of the same in the treatment of neurodegenerative diseases, neurodevelopmental disorders, age-related cognitive impairment, and age-related memory impairment.BACKGROUND

[0004] Insulin-like growth factor 2 (IGF-2, also called IGF2 and IGF-II) is a polypeptide with structural homology to insulin and, together with insulin-like growth factor 1 (IGF-1), belongs to the IGF / IGFBP system. IGF-2 expression and functions are still poorly characterized: in the adult tissues, its expression remains relatively high in brain regions, including the hippocampus, but is also found in the hypothalamus, striatum, cortex and cerebellum and declines with aging. Numerous studies indicated that IGF-2 and IGF-1 play similar functions including promoting neuronal survival and protection against injury; however, these effects are likely due to the activation of the IGF-1 receptor. IGF-2 in fact has been found to be involvedin promoting neuronal survival, proliferation and maturation, reduction of neuronal loss in adult brain following hypoxic-ischemic injury, protection of oligodendrocytes and hippocampal septal neurons, neurite outgrowth and direct sprouting of spared afferent into a de-afferent hippocampus. These effects may occur via IGF-1 receptor to which IGF -2 can bind with low affinity, hence the activation of the IGF-1 pathway. IGF-2, however, has shown distinct functions via activation of the high affinity receptor for IGF-2 or IGF-2 receptor (IGF-2R) also known as cation-independent mannose-6-phosphate receptor (CIM6PR).

[0005] IGF-2 has also been found to be involved in synaptic plasticity and memory. In addition it has been shown to reverse several behavioral deficits in a variety of brain disorders. Administration of recombinant IGF-2, either intracerebrally or systemically (subcutaneously, s.c.), in healthy animals (rats and / or mice) significantly enhances memory retention and persistence. In BTBR T+ Itpr3tf / J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of autism spectrum disorder (ASD), a s.c. injection of IGF-2 reverses cognitive and social impairments, as well as repetitive behaviors, and significantly ameliorates the underlying deficits of the AMPK-mTOR-S6K pathway and hyperactive rate of protein synthesis. A s.c. injection of IGF-2 or mannose-6-phosphate, another ligand of the IGF-2 receptor, reverses cognitive impairments, motor deficits and repetitive behavior in mice (Ube3a m- / p+ thereafter AS mice) modeling Angelman syndrome (AS). IGF-2 also protects AS mice from seizures. IGF-2 injected into the hippocampus reverses aging-related memory loss in rats. Furthermore, IGF-2 hippocampal overexpression or intraventricular injection rescues memory impairments, amyloid plaque load, and cholinergic dysfunctions in multiple mouse models of Alzheimer’s disease. Finally, IGF-2 is neuro-protective in models of neuronal oxidative damage. Where assessed, these positive effects of IGF-2 were found to be mediated by its high-affinity receptor, the IGF-2 receptor (IGF-2R), also known as cation-independent mannose-6-phosphate receptor (CIM6PR), and not by the IGF-1 receptor (IGF-1R) to which IGF-2 can bind with lower affinity.

[0006] IGF-2 binds with high affinity to the insulin like growth factor 2 receptor (CIM6P / IGF-2R). CIM6P / IGF-2R is a single transmembrane protein that belongs to the IGF / insulin system but acts distinctively from the other receptors of this system, i.e., IGF-1R and insulin receptors. In fact, while IGF-1 receptor and Insulin receptors (IRs) are receptor tyrosine kinase linked to the activation of the classical growth pathways involved in cell growth, proliferation, and survival, IGF-2R binds mannose 6 phosphate (M6P) (generally conjugated to proteins) as well as to IGF-2. The main known function of IGF-2R is to traffic lysosomal enzymes to lysosomes and IGF-2 to lysosomes for degradation. Recent studies showed that IGF-2R expressed in thebrain, and particularly the hippocampus, is required for memory formation by controlling de novo protein synthesis induced by learning (Yu et al. 2020;9:e54781. doi: 10.7554 / eLife.54781;2020).

[0007] IGF -2 has been shown to significantly enhance memory retention and prevent forgetting. This effect occurs via IGF-2R and not IGF- 1R (Chen, et al. Nature 2011; 469(7331): 491-497; Stern, et al. Learn Mem. 2014, 16; 21(10):556-63; Steinmetz et al. JNeurosci. 2018, 38(4): 1015-1029). IGF-2 reverses aging memory loss. (Steinmetz, et al. Neurobiol Aging.2016;44:9-21. doi: 10.1016 / j.neurobiolaging.2016.04.006.)

[0008] Additionally, IGF-2 has been shown to reverse multiple deficits in Alzheimer’s disease (“AD”) models. (Pascual-Lucas, et al. EMBO Mol Med. 2014; 6(10): 1246-62; Mellott, et al. PLoS One. 2014; 9(4):e94287; Kar, et al. Neurobiol Aging. 2006; 27(2): 199-210; Xia et al. Int Psychogeriatr. 2019, 31:7, 947-959.) These studies demonstrated that IGF-2 administration or overexpression is effective in reversing and preventing several pathophysiologic processes associated with AD and suggest that IGF-2 may constitute a therapeutic target for AD.

[0009] Additionally, IGF-2 has been shown to reverse most core deficits in autism spectrum disorder models via IGF-2R (Steinmetz et al. J Neurosci. 2018, 38(4):1015-1029; Pardo et al. JCI Insight. 2017, 2(6): e91782), protect against Huntington’s Disease (Garcia-Huerta et al. ActaNeuropathol. 2020 Nov; 140(5):737-764) and against amyotrophic lateral sclerosis (ALS). (Allodi, et al. Sci Rep. 2016;6:25960. doi: 10.1038 / srep25960; Osborn, et al. 2018;110:218-230.)

[0010] Mannose-6-phosphate (M6P), the structure of which is provided below, and IGF-2 have both been shown to reverse cognitive impairments, motor deficits, repetitive behaviors, and for IGF-2 also seizures, in Angelman syndrome mouse model (Cruz et al. Autism Research 14: 29-45, 2021.)OiiHO-Px_ mannose-6-phosphateHO O M6PI OH HO^A-I-O

[0011] Moreover, both IGF-2 and M6P were demonstrated to enhance memory strength and persistence in healthy rats and mice. (Yu, et al. 2020;9:e54781. doi: 10.7554 / eLife.54781; Chen, et al. Nature. 2011; 469(7331):491-7; Stern, et al. Neuropsychopharmacology 2014;39(9):2179-90; Agis-Balboa, et al. EMBO J. 2011;30(19):4071-83., Cruz et al. Cruz et al. Autism Research 14: 29-45, 2021; Steinmetz et al. JNeurosci. 2018, 38(4): 1015-1029).SUMMARY

[0012] In one aspect, this application pertains to a compound of Formula (I’):R7OR2t2o-^ -1-0 R2O-r3(I’), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;R1is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl;alternatively, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R6, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl,-0(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0013] In one embodiment, X is O.

[0014] In one embodiment, X is C(Y1)(Y2).

[0015] In one embodiment, Y1and Y2are each H.

[0016] In one embodiment, R1is Ci-Ce alkyl.

[0017] In one embodiment, R1is methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, or tert-butyl.

[0018] In one embodiment, R1is methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.

[0019] In one embodiment, each R2is H.

[0020] In one embodiment, at least one R2is -(CH2)m-Z-C(=O)-Rx.

[0021] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx.

[0022] In one embodiment, m is 0 and Z is absent.

[0023] In one embodiment, m is 1 and Z is O.

[0024] In one embodiment, Rxis Ci-Ce alkyl.

[0025] In one embodiment, Rxis methyl.

[0026] In one embodiment, at least one Rxis Ci-Ce alkyl.

[0027] In one embodiment, at least one Rxis methyl.

[0028] In one embodiment, R3is H.

[0029] In one embodiment, R3is Ci-Ce alkyl, C2-Ce alkenyl, or C2-Ce alkynyl.

[0030] In one embodiment, R3is N(Ry)2, SRy, or S(=O)nRy.

[0031] In one embodiment, R3is O(Ry).

[0032] In one embodiment, R5is H or Ci-Ce alkyl.

[0033] In one embodiment, R5is H.

[0034] In one embodiment, R5is Ci-Ce alkyl.

[0035] In one embodiment, R5is heterocyclyl, aryl, or heteroaryl.

[0036] In one embodiment, R5is heterocyclyl.

[0037] In one embodiment, R5is aryl.

[0038] In one embodiment, R5is heteroaryl.

[0039] In one embodiment, R5is H, methyl, iso-propyl, iso-butyl, sec-butyl, -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl, substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0040] In one embodiment, R6is H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, C3-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;

[0041] In one embodiment, R6is C3-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl.

[0042] In one embodiment, R6is aryl or heteroaryl;

[0043] In one embodiment, R6is C3-Cs cycloalkyl or heterocyclyl.

[0044] In one embodiment, R6is H or Ci-Ce alkyl.

[0045] In one embodiment, R6is H.

[0046] In one embodiment, R6is Ci-Ce alkyl.

[0047] In one embodiment, R7is H.

[0048] In one embodiment, R7is Ci-C3alkyl.

[0049] In one embodiment, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring.

[0050] In one embodiment, each Ryis, independently, Ci-Ce alkyl, C2-Ce alkenyl, or C2-Ce alkynyl.

[0051] In one embodiment, Ryis Ci-Ce alkyl.

[0052] In one embodiment, Ryis Ci-Ce alkyl substituted by at least one of -O(R), -N(R)2, or -N(R)-C(=O)-R.

[0053] In one embodiment, Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R.

[0054] In one embodiment, eachRis, independently, hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[0055] In one embodiment, the compound of Formula (I’) is a compound of Formula (Fa),R1OOCr3(Fa), wherein R1, R3, R5, R6and R7are as defined herein.

[0056] In one embodiment, the compound is of Formula (I’a),R1is H, Ci-Ce alkyl;R3is O(Ry), N(Ry)2;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is Ci-Ce alkyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkynyl.

[0057] In one embodiment, the compound is of Formula (I’a),R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl, aryl, or heteroaryl;R6is C3-C8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; and

[0058] each Ryis, independently, H, Ci-Ce alkyl. In one embodiment, the compound is of Formula (I’a),R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl;R6is aryl, or heteroaryl;R7is C1-C3 alkyl; andeach Ryis, independently, Ci-Ce alkyl.

[0059] In one embodiment, the compound of Formula (F) is a compound of Formula (I’b),R7OHHO-"' -1-0HO—r3(I’b), wherein R1, R3, R5, R6and R7are as defined herein.

[0060] In one embodiment, the compound is of Formula (I’b), whereinR1is H, Ci-Ce alkyl;R3is O(Ry), N(Ry)2;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is Ci-Ce alkyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkynyl.

[0061] In one embodiment, the compound is of Formula (I’b), whereinR1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl, aryl, or heteroaryl;R6is Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl.

[0062] In one embodiment, the compound is of Formula (I’b), whereinR1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl;R6is aryl, or heteroaryl;R7is C1-C3 alkyl; andeach Ryis, independently, Ci-Ce alkyl.

[0063] In one embodiment, the compound of Formula (I’) is a compound of Formula (Fc),(I’c), wherein R1, R3, R5, R6and R7are as defined herein.

[0064] In one embodiment, the compound of Formula (F) is a compound of Formula (I’d),(I’d), wherein R1, R3, R5, R6and R7are as defined herein.

[0065] In one embodiment, the compound of Formula (F) is a compound of Formula (Fe),(I’e), wherein R1, R3, R5, R6and R7are as defined herein.

[0066] In one embodiment, the compound of Formula (F) is a compound of Formula (I’f),(I’f), wherein R1, R3, R5, R6and R7are as defined herein.

[0067] In one embodiment, the compound is of Formula (I’c), Formula (I’d), Formula (I’e), Formula (I’f), wherein:R1is H, Ci-Ce alkyl;R3is O(Ry), N(Ry)2;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is Ci-Ce alkyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkynyl.

[0068] In one embodiment, the compound is of Formula (Fc), Formula (I’d), Formula (I’e), Formula (I’f), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl, aryl, or heteroaryl;R6is C3-C8 cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl.

[0069] In one embodiment, the compound is of Formula (I’c), Formula (I’d), Formula (I’e), Formula (I’f), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl;R6is aryl, or heteroaryl;R7is C1-C3 alkyl; andeach Ryis, independently, Ci-Ce alkyl.

[0070] In one embodiment, the compound of Formula (I) is a compound of Formula (I’g),R61ROOC^ XN^ % \°R7 / O^OAc AcO^°'^V^h°\ i R3AcO (I’g) wherein R1, R3, R5, R6, and R7are as defined herein.

[0071] In one embodiment, the compound of Formula (I) is a compound of Formula (I’h), R6x V°1ROOC^XPQ R7 / O^OAc AcO^°XX^|'°\ i o3AcO (Fh) wherein R1, R3, R5, R6, and R7are as defined herein.

[0072] The application also pertains, in one embodiment, to a pharmaceutical composition comprising a compound of Formula (F), and one or more pharmaceutically acceptable excipients.

[0073] In one embodiment, the one or more pharmaceutically acceptable excipients is selected from the group consisting of antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.

[0074] The application also pertains, in one embodiment, to a method of treating a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (F),R6R5o'R1OOC N \1,XR7 / OR2R2O-^? A-|-qR2°-^^\r3(I’), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is C(Y1)(Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;R1is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl;alternatively, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R6, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0075] In one embodiment, the neurodegenerative disease is amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease

[0076] In one embodiment, the neurodevelopmental disorder is an autism spectrum disorder.

[0077] In one embodiment, the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, Angelman syndrome, or pervasive developmental disorders-not otherwise specified.

[0078] In one embodiment, the compound of Formula (I’) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.

[0079] In one aspect, this application pertains to a compound of Formula (I”): COOR1R1OOC R2O R2r3(I”), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;each R5is, independently, H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;each R7is, independently, H or C1-C3 alkyl;alternatively, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, - O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)- O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0080] In one embodiment, X is O.

[0081] In one embodiment, X is C(Y1)(Y2).

[0082] In one embodiment, Y1and Y2are each H.

[0083] In one embodiment, each R1is, independently, Ci-Ce alkyl.

[0084] In one embodiment, at least one R1is, independently, methyl, ethyl, n-propyl, isopropyl, iso-butyl, sec-butyl, or tert-butyl.

[0085] In one embodiment, each R1is, independently, methyl, ethyl, n-propyl, iso-propyl, isobutyl, sec-butyl, or tert-butyl.

[0086] In one embodiment, at least one R1is, independently, methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.

[0087] In one embodiment, each R1is, independently, methyl, ethyl, n-propyl, iso-butyl, secbutyl, or tert-butyl.

[0088] In one embodiment, each R2is H.

[0089] In one embodiment, at least one R2is -(CH2)m-Z-C(=O)-Rx.

[0090] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx.

[0091] In one embodiment, m is 0 and Z is absent.

[0092] In one embodiment, m is 1 and Z is O.

[0093] In one embodiment, Rxis Ci-Ce alkyl.

[0094] In one embodiment, Rxis methyl.

[0095] In one embodiment, at least one Rxis Ci-Ce alkyl.

[0096] In one embodiment, at least one Rxis methyl.

[0097] In one embodiment, R3is H.

[0098] In one embodiment, R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[0099] In one embodiment, R3is N(Ry)2, SRy, or S(=O)nRy.

[0100] In one embodiment, R3is O(Ry).

[0101] In one embodiment, each R5is, independently, H or Ci-Ce alkyl.

[0102] In one embodiment, each R5is H.

[0103] In one embodiment, at least one R5is Ci-Ce alkyl.

[0104] In one embodiment, each R5is Ci-Ce alkyl.

[0105] In one embodiment, at least one R5is, independently, heterocyclyl, aryl, or heteroaryl.

[0106] In one embodiment, at least one R5is heterocyclyl.

[0107] In one embodiment, at least one R5is aryl.

[0108] In one embodiment, at least one R5is heteroaryl.

[0109] In one embodiment, each R5is, independently, H, methyl, iso-propyl, iso-butyl, secbutyl, -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by / / ra-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0110] In one embodiment, each R7is H.

[0111] In one embodiment, at least one R7is Ci-C3alkyl.

[0112] In one embodiment, each R7is Ci-C3alkyl.

[0113] In one embodiment, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring.

[0114] In one embodiment, each Ryis, independently, Ci-Ce alkyl, C2-Ce alkenyl, or C2-Ce alkynyl.

[0115] In one embodiment, Ryis Ci-Ce alkyl.

[0116] In one embodiment, Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)- C(=O)-R.

[0117] In one embodiment, eachRis, independently, hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[0118] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”a),COOR1R5.N OH HO-l-oMOr3(I”a), wherein R1, R3, R5, and R7are as defined herein.

[0119] In one embodiment, the compound is of Formula (I”a), wherein:R1is H, Ci-Ce alkyl;R3is O(Ry), N(Ry)2;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R7is H or Ci-C3alkyl; andeach Ryis, independently, H, Ci-Ce alkyl, C2-Ce alkynyl.

[0120] In one embodiment, the compound is of Formula (I”a), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl, aryl, or heteroaryl;R7is H or Ci-C3alkyl; andeach Ryis, independently, H, Ci-Ce alkyl.

[0121] In one embodiment, the compound is of Formula (I”a), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl;R7is C1-C3 alkyl; andeach Ryis, independently, Ci-Ce alkyl.

[0122] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”b),(I”b), wherein R1, R3, R5, and R7are as defined herein.

[0123] In one embodiment, the compound is of Formula (I”b), wherein:R1is H, Ci-Ce alkyl;R3is O(Ry), N(Ry)2;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkynyl.

[0124] In one embodiment, the compound is of Formula (I”b), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl; andeach Ryis, independently, H, Ci-Ce alkyl.

[0125] In one embodiment, the compound is of Formula (I”b), wherein:R1is Ci-Ce alkyl;R3is O(Ry);R5is H, Ci-Ce alkyl;R7is C1-C3 alkyl; andeach Ryis, independently, Ci-Ce alkyl.

[0126] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”c), R51ROOC-^R71XROOC^~N^N'pP-°\R7 / O^OAcAcO^O'X^|'°\R3AcO (I”c), wherein R1, R3, R5, and R7are as defined herein.

[0127] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”d),R51ROOC-^R71XN'p"°ROOC^~N^P\OR7 / O^OAcAcO^OX'^l'A

[0128] AcO (I”d), wherein R1, R3, R5, and R7are as defined herein. The application also pertains, in one embodiment, to a pharmaceutical composition comprising a compound of Formula (I”), and one or more pharmaceutically acceptable excipients.

[0129] In one embodiment, the one or more pharmaceutically acceptable excipients is selected from the group consisting of: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.

[0130] The application also pertains, in one embodiment, to a method of treating a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I”):(I”), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is CXXY2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;each R5is, independently, H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;each R7is, independently, H or C1-C3 alkyl;alternatively, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0131] In one embodiment, the neurodegenerative disease is amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease.

[0132] In one embodiment, the neurodegenerative disease is amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease, or Alzheimer’s disease.

[0133] In one embodiment, the neurodevelopmental disorder is an autism spectrum disorder.

[0134] In one embodiment, the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, Angelman syndrome, or pervasive developmental disorders-not otherwise specified.

[0135] In one embodiment, the compound of Formula (I”) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.

[0136] In one aspect, this application pertains to a compound of Formula (I):(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=O)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2,provided that:when X is C(Y1)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis not methyl or propargyl; andwhen X is C(YX)(Y2); Y1and Y2are each H; each R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis not 2,4-dimethylphenyl.

[0137] In one embodiment, the compound is of Formula (I), whereinR1is H, Ci-Ce alkyl;each R2is, independently, H, Ci-Ce alkyl, or -(CH2)m-Z-C(=O)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is O(Ry), N(Ry)2;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkynyl.

[0138] In one embodiment, the compound is of Formula (I), whereinR1is Ci-Ce alkyl;each R2is, independently, H, Ci-Ce alkyl,R3is O(Ry);each Ryis, independently, H, Ci-Ce alkyl.

[0139] In one embodiment, the compound is of Formula (I), whereinR1is Ci-Ce alkyl;each R2is, independently, H,or -(CH2)m-Z-C(=O)-Rx;each Rxis, independently, H, Ci-Ce alkyl;R3is O(Ry);each Ryis, independently, Ci-Ce alkyl.

[0140] In one embodiment, X is O.

[0141] In one embodiment, X is C(Y1)(Y2).

[0142] In one embodiment, Y1and Y2are each H.

[0143] In one embodiment, each R1is, independently, Ci-Ce alkyl.

[0144] In one embodiment, each R1is, independently, methyl, ethyl, n-propyl, iso-propyl, isobutyl, sec-butyl, or tert-butyl.

[0145] In one embodiment, each R1is, independently, methyl, ethyl, n-propyl, iso-butyl, secbutyl, or tert-butyl.

[0146] In one embodiment, each R2is H.

[0147] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx.

[0148] In one embodiment, m is 0 and Z is absent.

[0149] In one embodiment, m is 1 and Z is O.

[0150] In one embodiment, Rxis Ci-Ce alkyl.

[0151] In one embodiment, Rxis methyl.

[0152] In one embodiment, R3is H.

[0153] In one embodiment, R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[0154] In one embodiment, R3is N(Ry)2, SRy, or S(=O)nRy.

[0155] In one embodiment, R3is O(Ry).

[0156] In one embodiment, Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[0157] In one embodiment, Ryis Ci-Ce alkyl.

[0158] In one embodiment, Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)- C(=O)-R.

[0159] In one embodiment, each Ris hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[0160] In one embodiment, the compound of Formula (I) is a compound of Formula (la),R3(Ia), wherein R1and R3are as defined herein.

[0161] In one embodiment, the compound of Formula (I) is a compound of Formula (lb),(Ib> wherein R1and R3are as defined herein.

[0162] In one embodiment, the compound of Formula (I) is a compound of Formula (Ic),wherein R1and R3are as defined herein.

[0163] In one embodiment, the compound of Formula (I) is a compound of Formula (Id),wherein R1and R3are as defined herein.

[0164] The application also pertains, in one embodiment, to a pharmaceutical composition comprising a compound of Formula (I), and one or more pharmaceutically acceptable excipients.

[0165] In one embodiment, the one or more pharmaceutically acceptable excipients is selected from the group consisting of antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.

[0166] The application also pertains, in one embodiment, to a method of treating a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I),(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl,-0(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=0)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0167] In one embodiment, the neurodevelopmental disorder is Angelman syndrome.

[0168] In one embodiment, the neurodegenerative disease is, amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease

[0169] In one embodiment, the neurodevelopmental disorder is an autism spectrum disorder.

[0170] In one embodiment, the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, or pervasive developmental disorders-not otherwise specified.

[0171] In one embodiment, the compound of Formula (I), (I’), or (I”) or any of the formulae disclosed herein is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.BRIEF DESCRIPTION OF THE FIGURES

[0172] FIG. 1 depicts a dose response curve of Compound 1 in novel object recognition (nOR).

[0173] FIG. 2 depicts a dose response curve of Compound 2 in novel object recognition (nOR).

[0174] FIG. 3 depicts a dose response curve of Compound 1 in contextual fear conditioning (CFC).

[0175] FIG. 4 depicts a dose response curve of Compound Bl in novel object recognition (nOR).

[0176] FIG. 5 depicts a dose response curve of Compound Bl in contextual fear conditioning (CFC).DETAILED DESCRIPTION

[0177] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which the inventionpertains. Specific terminology of particular importance to the description of the present invention is defined below.

[0178] It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise.

[0179] As used herein, the term "patient" or "individual" or "subject" refers to any person or mammalian subject for whom or which therapy is desired, and generally refers to the recipient of the therapy to be practiced according to the invention. In one embodiment, the subject is a human.

[0180] “Administration” refers to introducing a pharmaceutical formulation as described herein into a subject. The related terms “administering” and “administration of’ (and grammatical equivalents) refer both to direct administration, which may be administration to a subject by a medical professional or by self-administration by the subject, and / or to indirect administration, which may be the act of prescribing a drug such as a pharmaceutical formulation described herein. For example, a physician who instructs a subject to selfadminister a pharmaceutical formulation described herein and / or provides a subject with a prescription for a pharmaceutical formulation described herein is administering the pharmaceutical formulation to the patient.

[0181] “Comprising” or “comprises” as applied to a particular pharmaceutical formulation or method described or claimed herein means that the pharmaceutical formulation or method includes all of the recited elements in a specific description or claim, but does not exclude other elements. “Consists essentially of’ and “consisting essentially of’ means that the described or claimed pharmaceutical formulation or method does not exclude other materials or steps that do not materially affect the recited physical, pharmacological, pharmacokinetic properties or therapeutic effects of the composition, dosage form, method or process. “Consists of’ and “consisting of’ means the exclusion of more than trace elements of other ingredients and substantial method or process steps.

[0182] All amounts of a component of an oral dosage form described herein that are indicated based on % w / w refer to the total weight of the oral dosage form, unless otherwise indicated.

[0183] The term “about” as part of a quantitative expression such as “about X”, includes any value that is 10% higher or lower than X, and also includes any numerical value that falls between X-10% and X+10%. Thus, for example, a weight of about 40 g includes a weight of between 36 to 44 g.

[0184] “Treating” or “treatment” of a state, disorder or condition includes: preventing or delaying the appearance or slowing down the progression of clinical or sub-clinical symptomsof the state, disorder or condition developing in a mammal that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; or inhibiting the state, disorder or condition, e.g., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or sub-clinical symptom thereof; or relieving the disease, e.g., causing regression of the state, disorder or condition or at least one of its clinical or sub-clinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the subject or to the person administering the treatment (e.g., a physician).

[0185] The term “therapeutically effective amount” as used herein is the amount sufficient to achieve, in a single or multiple doses, the intended purpose of treatment. For example, an effective amount to treat an autism spectrum disorder is an amount sufficient to alleviate or eliminate the symptoms of the autism spectrum disorder. The exact amount desired or required will vary depending on the mode of administration, patient specifics and the like. Appropriate effective amounts can be determined by one of ordinary skill in the art (such as a clinician) with the benefit of the present disclosure.

[0186] Representative "pharmaceutically acceptable salts" include, e.g., water-soluble and water-insoluble salts, such as the acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzonate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fumerate, fiunarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methyl sulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (l,l-methene-bis-2-hydroxy-3 -naphthoate, einbonate), pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, subacetate, succinate, sulfate, sulfosalicylate, suramate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate salts.

[0187] The term "solvate" refers to a complex of variable stoichiometry formed by a solute and solvent. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates wherein water is the solvent molecule are typically referred to as hydrates. Hydrates include compositions containing stoichiometric amounts of water, as well as compositions containing variable amounts of water.

[0188] “Alkyl” refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms.

[0189] “ Ci-Ce alkyl” refers to a methyl, ethyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl iso-pentyl, neo-pentyl, n-hexyl, or iso-hexyl group.

[0190] “ C1-C4 alkyl” refers to a methyl, ethyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or tert-butyl group.

[0191] “Alkenyl” refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkenyl” group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, iso-butenyl, pentenyl, or hexenyl. An alkenyl group can be unsubstituted or substituted. Alkenyl, as herein defined, may be straight or branched.

[0192] “Alkynyl” refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The “alkynyl” group contains at least one triple bond (C=C) in the chain.=Examples of alkenyl groups include ethynyl, propargyl( ), n-butynyl, iso-butynyl, pentynyl, or hexynyl. An alkynyl group can be unsubstituted or substituted.

[0193] “Cycloalkyl” refers to a monocyclic saturated carbon ring containing 3-18 carbon atoms. Example of cycloalkyl groups also include partially unsaturated cycloalkyl groups that have one or more double or triple bonds. Examples of cycloalkyl groups include, without limitations, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptanyl, cyclooctanyl, cyclooctynyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl.

[0194] “Heterocyclyl” or “heterocycloalkyl” monocyclic rings containing carbon and one or more ring heteroatoms selected from N, O, S, P, or B and wherein there are not delocalized n electrons (aromaticity) shared among the ring carbon or heteroatoms. The heterocycloalkyl ring structure may be substituted by one or more substituents. The substituents can themselves be optionally substituted. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, and homotropanyl.

[0195] The term "aryl" refers to cyclic, aromatic hydrocarbon groups that have 1, 2, or 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl.When containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group may be joined at a single point (e.g., biphenyl), or fused (e.g., naphthyl). The aryl group may be optionally substituted by one or more substituents, e.g., 1 to 5 substituents, at any point of attachment. The substituents can themselves be optionally substituted. Furthermore, when containing two fused rings the aryl groups herein defined may have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannulenyl, and the like.

[0196] " Heteroaryl" means a monovalent monocyclic or polycyclic aromatic group that has 5 to 24 ring atoms, wherein one or more ring atoms is a heteroatom selected from N, O, S, P, or B, with the remaining ring atoms being carbon. The heteroaryl group may be optionally substituted by one or more substituents, e.g., 1 to 5 substituents, at any point of attachment. The substituents can themselves be optionally substituted. Examples include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolinyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[l,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[l,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][l,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolof l,5-a]pyridinyl, [l,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[l,2-a]pyrimidinyl, tetrahydro pyrrolo[l,2-a]pyrimidinyl, 3,4-dihydro-2H-ll2-pyrrolo[2,l-b]pyrimidine, dibenzo[b,d] thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, lH-pyrido[3,4-b][l,4] thiazinyl, benzoxazolyl, benzisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [l,2,4]triazolo[l,5-a]pyridinyl, benzo [l,2,3]triazolyl, imidazo[l,2-a]pyrimidinyl, [l,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][l,2,5]thiadiazolyl, benzo[c][l,2,5]oxadiazole, l,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo [l,5-b][l,2]oxazinyl, 4, 5,6,7-tetrahydropyrazolo[l,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl, imidazo[2, 1-b][l,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl, and derivatives thereof. Furthermore,when containing two or more fused rings, the heteroaryl groups defined herein may have one or more saturated or partially unsaturated ring fused with a fully unsaturated ring, e.g., a 5-membered heteroaromatic ring containing 1-3 heteroatoms selected from N, S, or O, or a 6-membered heteroaromatic ring containing 1-3 nitrogens, fused to a saturated or partially unsaturated ring with 0-4 heteroatoms selected from N, O, S, P, or B, and is optionally substituted with one or more oxo. In heteroaryl ring systems containing more than two fused rings, a saturated or partially unsaturated ring may further be fused with a saturated or partially unsaturated ring described herein. Exemplary ring systems of these heteroaryl groups include, for example, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-lH-isoquinolinyl, 2,3-dihydrobenzofuranyl, benzofuranonyl, indolinyl, oxindolyl, indolyl, l,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-onyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolizinyl, 8H-pyrido[3,2-b]pyrrolizinyl, l,5,6,7-tetrahydrocyclopenta[b]pyrazolo[4,3-e]pyridinyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolizine, pyrazolo[l,5-a]pyrimidin-7(4H)-only, 3,4-dihydropyrazino[l,2-a]indol-l(2H)-onyl, or benzofc] [l,2]oxaborol-l(3Z / )-olyl.

[0197] In one embodiment, the heteroaryl group isCe alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl; and X' is a counterion such as fluoride, chloride, bromide, iodide, tritiate, tosylate, or the like.

[0198] As used herein, “cholesteryl” refers to the following moiety:

[0199] The term “haloalkyl” as used herein refers to an alkyl group, as defined herein, which is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc.

[0200] “Halogen” or “halo” refers to fluorine, chlorine, bromine, or iodine.

[0201] “Alkoxy” refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms containing a terminal “O” in the chain, i.e., -O(alkyl). Examples of alkoxy groups include without limitation, methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentoxy groups.

[0202] “Haloalkoxy” refers to an alkoxy as defined herein, which is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluromethoxy and pentafluorethoxy.

[0203] “ Stereoisomer”, as used herein, refers to a diastereomer or enantiomer. Included within the definition of a diastereomer is an epimer - a stereoisomer that differs in configuration at any single stereogenic center. Further included within the definition of a diastereomer is an anomer, which is an epimer at the anomeric carbon of a carbohydrate molecule.

[0204] As used herein, the designation refers to a mixture of alpha and beta epimers at the indicated carbon atom. For instance, the compound of Formula (I’) is a mixture of alpha and beta epimers, or alpha and beta anomers when R3is O(Ry).

[0205] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.COMPOUNDS OF THE APPLICATION

[0206] In one aspect, this application pertains to a compound of Formula (F),(F), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:Xis CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;R1is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=O)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl;alternatively, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R6, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0207] In one embodiment, when X is C(Y1)(Y2); Y1and Y2are each H; R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis H, C2-C6 alkyl, C2-C6 alkenyl, C4-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy.

[0208] In one embodiment, when X is C(Y1)(Y2); Y1and Y2are each H; R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, or heteroaryl.

[0209] In one embodiment, X is C(Y1)(Y2).

[0210] In one embodiment, in the compound of Formula (I’), Y1and Y2are the same. For example, Y1and Y2are both H, Y1and Y2are both halo, or Y1and Y2are both Ci-Ce alkyl.

[0211] In one embodiment, Y1and Y2are both fluoro.

[0212] In one embodiment, Y1and Y2are methyl.

[0213] In one embodiment, in the compound of Formula (F), Y1and Y2are the different.

[0214] In one embodiment, Y1is H and Y2is OH, halo, or Ci-Ce alkyl.

[0215] In one embodiment, Y1is H and Y2is OH. In one embodiment, Y1is H and Y2is halo. In one embodiment, Y1is H and Y2is Ci-Ce alkyl.

[0216] In one embodiment, X is C(=O).

[0217] In one embodiment, X is O.

[0218] In one embodiment, R1is H.

[0219] In one embodiment, R1is Ci-Ce alkyl.

[0220] In one embodiment, R1is methyl.

[0221] In one embodiment, R1is ethyl.

[0222] In one embodiment, R1is n-propyl.

[0223] In one embodiment, R1is iso-propyl.

[0224] In one embodiment, R1is iso-butyl.

[0225] In one embodiment, R1is sec-butyl.

[0226] In one embodiment, R1is tert-butyl.

[0227] In one embodiment, R1is n-butyl.

[0228] In one embodiment, R1is C5 alkyl.

[0229] In one embodiment, R1is Ce alkyl.

[0230] In one embodiment, R1is C2-C6 alkenyl.

[0231] In one embodiment, R1is C2-C6 alkynyl.

[0232] In one embodiment, R1is C3-C8cycloalkyl.

[0233] In one embodiment, R1is heterocyclyl.

[0234] In one embodiment, R1is aryl.

[0235] In one embodiment, R1is heteroaryl.

[0236] In one embodiment, R1is cholesteryl.

[0237] In one embodiment, each of R2in the compound of Formula (I’) is the same. For example, each R2is H or each R2is -(CH2)m-Z-C(=O)-Rx.

[0238] In one embodiment, each R2is H.

[0239] In one embodiment, each R2is Ci-Ce alkyl.

[0240] In one embodiment, each R2is C2-C6 alkenyl.

[0241] In one embodiment, each R2is C2-C6 alkynyl.

[0242] In one embodiment, each R2is C3-C8cycloalkyl.

[0243] In one embodiment, each R2is heterocyclyl.

[0244] In one embodiment, each R2is aryl.

[0245] In one embodiment, each R2is heteroaryl.

[0246] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis H.

[0247] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis Ci-Ce alkyl.

[0248] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkenyl.

[0249] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkynyl.

[0250] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C3-C8cycloalkyl.

[0251] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heterocyclyl.

[0252] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis aryl.

[0253] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heteroaryl.

[0254] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 0.

[0255] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 1.

[0256] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 2.

[0257] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 3.

[0258] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 4.

[0259] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 5.

[0260] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 6.

[0261] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 7.

[0262] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 8.

[0263] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 9.

[0264] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 10.

[0265] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 0, and Z is absent.

[0266] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is absent.

[0267] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is O.

[0268] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is absent.

[0269] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is O.

[0270] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is absent.

[0271] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is O.

[0272] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is absent.

[0273] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is O.

[0274] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is absent.

[0275] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is O.

[0276] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is absent.

[0277] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is O.

[0278] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is absent.

[0279] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is O.

[0280] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is absent.

[0281] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is O.

[0282] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is absent.

[0283] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is O.

[0284] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is absent.

[0285] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is O.

[0286] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent.

[0287] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is absent.

[0288] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O.

[0289] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is absent.

[0290] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is O.

[0291] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is absent.

[0292] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is O.

[0293] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is absent.

[0294] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is O.

[0295] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is absent.

[0296] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is O.

[0297] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is absent.

[0298] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is O.

[0299] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is absent.

[0300] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is O.

[0301] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is absent.

[0302] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is O.

[0303] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is absent.

[0304] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is O.

[0305] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is absent.

[0306] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is O.

[0307] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 0, and Z is absent.

[0308] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is absent.

[0309] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is O.

[0310] In one embodiment, two of R2in the compound of Formula (I’) are the same and the other R2is different. For example, two of R2is H or the other R2is -(CH2)m-Z-C(=O)-Rx; or two of R2is -(CH2)m-Z-C(=O)-Rxor the other R2is H.

[0311] In one embodiment, all three of R2in the compound of Formula (F) are different. For example, one of R2is H, one of R2is -(CH2)m-Z-C(=O)-Rx, and the other R2is Ci-Ce alkyl.

[0312] In one embodiment, Rxis H.

[0313] In one embodiment, Rxis Ci-Ce alkyl.

[0314] In one embodiment, Rxis methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, tertbutyl, Cs alkyl, or Ce alkyl.

[0315] In one embodiment, Rxis C2-C6 alkenyl.

[0316] In one embodiment, Rxis C2-C6 alkynyl.

[0317] In one embodiment, Rxis C3-C8cycloalkyl.

[0318] In one embodiment, Rxis heterocyclyl.

[0319] In one embodiment, Rxis aryl.

[0320] In one embodiment, Rxis heteroaryl.

[0321] In one embodiment, in the compound of Formula (F), R3is H.

[0322] In one embodiment, R3is Ci-Ce alkyl.

[0323] In one embodiment, R3is methyl.

[0324] In one embodiment, R3is ethyl.

[0325] In one embodiment, R3is n-propyl

[0326] In one embodiment, R3is iso-propyl

[0327] In one embodiment, R3is iso-butyl.

[0328] In one embodiment, R3is sec-butyl

[0329] In one embodiment, R3is tert-butyl

[0330] In one embodiment, R3is C5 alkyl.

[0331] In one embodiment, R3is Ce alkyl.

[0332] In one embodiment, R3is C2-C6 alkenyl,

[0333] In one embodiment, R3is C2-C6 alkynyl.

[0334] In one embodiment, R3is C3-C8cycloalkyl.

[0335] In one embodiment, R3is heterocyclyl.

[0336] In one embodiment, R3is aryl.

[0337] In one embodiment, R3is heteroaryl.

[0338] In one embodiment, R is O(Ry).

[0339] In one embodiment, R3is N(Ry)2.

[0340] In one embodiment, R3is SRy.

[0341] In one embodiment, R3is S(=O)nRy

[0342] In one embodiment, R5is H.

[0343] In one embodiment, R5is Ci-Ce alkyl.

[0344] In one embodiment, R5is Ci-Ce alkyl, substituted by one or more R.

[0345] In one embodiment, R5is methyl.

[0346] In one embodiment, R5is methyl, substituted by one or more R.

[0347] In one embodiment, R5is ethyl.

[0348] In one embodiment, R5is ethyl, substituted by one or more R.

[0349] In one embodiment, R5is n-propyl

[0350] In one embodiment, R5is iso-propyl

[0351] In one embodiment, R5is iso-butyl.

[0352] In one embodiment, R5is sec-butyl

[0353] In one embodiment, R5is tert-butyl

[0354] In one embodiment, R5is Cs alkyl.

[0355] In one embodiment, R5is Ce alkyl.

[0356] In one embodiment, R5is an amino acid side chain.

[0357] In one embodiment, R5is -CH2-NH2.

[0358] In one embodiment, R5is -CH2-OH.

[0359] In one embodiment, R5is -CH(-OH)-CH3.

[0360] In one embodiment, R5is -CH2-C(=O)-NH2.

[0361] In one embodiment, R5is -(CH2)2-C(=O)-NH2.

[0362] In one embodiment, R5is -CH2-COOH.

[0363] In one embodiment, R5is -(CH2)2-COOH.

[0364] In one embodiment, R5is -CH2-SH.

[0365] In one embodiment, R5is -CH2-S-CH3.

[0366] In one embodiment, R5is -(CH2)2-SH.

[0367] In one embodiment, R5is -(CH2)2-S-CH3.

[0368] In one embodiment, R5is -(CH2)2-NH-C(=NH)-NH2.

[0369] In one embodiment, R5is -(CH2)3-NH-C(=NH)-NH2.

[0370] In one embodiment, R5is -(CH2)4-NH-C(=NH)-NH2.

[0371] In one embodiment, R5is -(CH2)4-NH2.

[0372] In one embodiment, R5is -CH2-phenyl.

[0373] In one embodiment, R5is -CH2-phenyl, substituted by OH.

[0374] In one embodiment, R5is -CH2-phenyl, substituted by para-OH.

[0375] In one embodiment, R5is -CH2-heteroaryl.

[0376] In one embodiment, R5is -CH2-imidazolyl.

[0377] In one embodiment, R5is -CH2-heterocyclyl.

[0378] In one embodiment, R5is -CH2-indolyl.

[0379] In one embodiment, R5is heterocyclyl.

[0380] In one embodiment, R5is aryl.

[0381] In one embodiment, R5is heteroaryl.

[0382] In one embodiment, R6isH.

[0383] In one embodiment, R6is Ci-Ce alkyl.

[0384] In one embodiment, R6is methyl.

[0385] In one embodiment, R6is ethyl.

[0386] In one embodiment, R6is n-propyl

[0387] In one embodiment, R6is iso-propyl

[0388] In one embodiment, R6is iso-butyl.

[0389] In one embodiment, R6is sec-butyl

[0390] In one embodiment, R6is tert-butyl

[0391] In one embodiment, R6is Cs alkyl.

[0392] In one embodiment, R6is Ce alkyl.

[0393] In one embodiment, R6is C2-C6alkenyl.

[0394] In one embodiment, R6is allyl.

[0395] In one embodiment, R6is C2-C6alkynyl.

[0396] In one embodiment, R6is propargyl.

[0397] In one embodiment, R6is C3-C8cycloalkyl.

[0398] In one embodiment, R6is heterocyclyl.

[0399] In one embodiment, R6is aryl.

[0400] In one embodiment, R6is phenyl.

[0401] In one embodiment, R6is heteroaryl.

[0402] In one embodiment, R7is H.

[0403] In one embodiment, R7is C1-C3 alkyl.

[0404] In one embodiment, R7is methyl.

[0405] In one embodiment, R7is ethyl.

[0406] In one embodiment, R7is n-propyl

[0407] In one embodiment, R7is iso-propyl

[0408] In one embodiment, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring.

[0409] In one embodiment, R5and R7, together with the atoms they are attached to, form a pyrrolidine.

[0410] In one embodiment, R5and R7, together with the atoms they are attached to, form a pyrrolidine that is only substituted by the -COOR1moiety.

[0411] In one embodiment, R5and R7, together with the atoms they are attached to, form a pyrrolidine that substituted by one or more R in addition to being substituted by the -COOR1moiety, wherein each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH, or SH.

[0412] In one embodiment, each Ryis, independently, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[0413] In one embodiment, at least one Ryis Ci-Ce alkyl.

[0414] In one embodiment, at least one Ryis methyl.

[0415] In one embodiment, at least one Ryis ethyl.

[0416] In one embodiment, at least one Ryis n-propyl.

[0417] In one embodiment, at least one Ryis iso-propyl.

[0418] In one embodiment, at least one Ryis iso-butyl.

[0419] In one embodiment, at least one Ryis sec-butyl.

[0420] In one embodiment, at least one Ryis tert-butyl.

[0421] In one embodiment, at least one Ryis C5 alkyl.

[0422] In one embodiment, at least one Ryis Ce alkyl.

[0423] In one embodiment, at least one Ryis allyl.

[0424] In one embodiment, at least one Ryis propargyl.

[0425] In one embodiment, each Ryis, independently, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein each is substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[0426] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[0427] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein one R is hydrogen, and the other R is; wherein R is H, Ci-Ce alkyl, C2-C6 alkenyl, C2- Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl; and X' is a counterion selected from the group consisting of fluoride, chloride, bromide, iodide, tritiate, and tosylate.

[0428] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0429] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0430] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0431] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0432] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is aryl.

[0433] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is aryl.

[0434] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0435] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0436] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is phenyl.

[0437] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0438] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0439] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0440] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0441] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0442] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is aryl.

[0443] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is aryl.

[0444] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0445] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0446] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is phenyl.

[0447] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0448] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0449] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0450] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0451] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is H.

[0452] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is aryl; and R7is H.

[0453] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is aryl; and R7is H.

[0454] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0455] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is H.

[0456] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is phenyl; and R7is H.

[0457] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is H.

[0458] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0459] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0460] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0461] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is Me.

[0462] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is aryl; and R7is Me.

[0463] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is aryl; and R7is Me.

[0464] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0465] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is Me.

[0466] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is phenyl; and R7is Me.

[0467] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is Me.

[0468] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0469] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0470] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0471] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0472] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is aryl.

[0473] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is aryl.

[0474] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0475] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0476] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is phenyl.

[0477] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0478] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0479] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0480] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0481] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0482] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is aryl.

[0483] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is aryl.

[0484] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0485] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0486] In one embodiment, X is CH2; R1is propyl; R3is ethyl; and R6is phenyl.

[0487] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0488] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0489] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0490] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0491] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is H.

[0492] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is aryl; and R7is H.

[0493] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is aryl; and R7is H.

[0494] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0495] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is H.

[0496] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is phenyl; and R7is H.

[0497] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is H.

[0498] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0499] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0500] In one embodiment, X is CH2; X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0501] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is Me.

[0502] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is aryl; and R7is Me.

[0503] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is aryl; and R7is Me.

[0504] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0505] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is Me.

[0506] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R6is phenyl; and R7is Me.

[0507] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is Me.

[0508] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0509] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0510] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0511] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is aryl.

[0512] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is aryl.

[0513] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is aryl.

[0514] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0515] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0516] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0517] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0518] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0519] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0520] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0521] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is aryl.

[0522] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is aryl.

[0523] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is aryl.

[0524] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0525] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0526] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0527] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0528] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0529] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0530] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0531] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0532] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0533] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0534] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0535] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0536] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0537] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0538] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0539] In one embodiment, X is CH2; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0540] In one embodiment, X is CH2; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0541] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0542] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0543] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0544] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0545] In one embodiment, X is CH2; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0546] In one embodiment, X is CH2; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0547] In one embodiment, X is CH2; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0548] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0549] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0550] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0551] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0552] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is aryl.

[0553] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is aryl.

[0554] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0555] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0556] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is phenyl.

[0557] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0558] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0559] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0560] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0561] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0562] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is aryl.

[0563] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is aryl.

[0564] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0565] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0566] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is phenyl.

[0567] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0568] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0569] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0570] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0571] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is H.

[0572] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is aryl; and R7is H.

[0573] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is aryl; and R7is H.

[0574] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0575] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is H.

[0576] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is phenyl; and R7is H.

[0577] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is H.

[0578] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0579] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0580] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0581] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is Me.

[0582] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is aryl; and R7is Me.

[0583] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is aryl; and R7is Me.

[0584] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0585] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is Me.

[0586] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is phenyl; and R7is Me.

[0587] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is Me.

[0588] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0589] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0590] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0591] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0592] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is aryl.

[0593] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is aryl.

[0594] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0595] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0596] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is phenyl.

[0597] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0598] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is aryl.

[0599] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0600] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; and R6is aryl.

[0601] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is aryl.

[0602] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is aryl.

[0603] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is aryl.

[0604] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; and R6is phenyl.

[0605] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; and R6is phenyl.

[0606] In one embodiment, X is O; R1is propyl; R3is ethyl; and R6is phenyl.

[0607] In one embodiment, X is O; R1is iso-propyl; R3is propyl; and R6is phenyl.

[0608] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0609] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0610] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is H.

[0611] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is H.

[0612] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is aryl; and R7is H.

[0613] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is aryl; and R7is H.

[0614] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0615] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is H.

[0616] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is phenyl; and R7is H.

[0617] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is H.

[0618] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0619] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0620] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0621] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is aryl; and R7is Me.

[0622] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is aryl; and R7is Me.

[0623] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is aryl; and R7is Me.

[0624] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0625] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R6is phenyl; and R7is Me.

[0626] In one embodiment, X is O; R1is propyl; R3is ethyl; R6is phenyl; and R7is Me.

[0627] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R6is phenyl; and R7is Me.

[0628] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0629] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0630] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0631] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is aryl.

[0632] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is aryl.

[0633] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is aryl.

[0634] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0635] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0636] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0637] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0638] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0639] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0640] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is aryl.

[0641] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is aryl.

[0642] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is aryl.

[0643] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is aryl.

[0644] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0645] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0646] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0647] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; and R6is phenyl.

[0648] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0649] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0650] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0651] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0652] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0653] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is aryl; and R7is H.

[0654] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0655] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0656] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0657] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is H.

[0658] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0659] In one embodiment, X is O; R1is propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0660] In one embodiment, X is O; R1is iso-propyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0661] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0662] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0663] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is aryl; and R7is Me.

[0664] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is Ci-Ce alkyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0665] In one embodiment, X is O; R1is Ci-Ce alkyl; R3is methyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0666] In one embodiment, X is O; R1is propyl; R3is ethyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0667] In one embodiment, X is O; R1is iso-propyl; R3is propyl; R5is Ci-Ce alkyl; R6is phenyl; and R7is Me.

[0668] In one aspect, this application pertains to a compound of Formula (F) that is a compound of Formula (Fa),R1OOC'X^'NxIR7OHHO" -l-OHO(Fa), wherein R1, R3, R5, R6and R7are as defined herein.

[0669] In one aspect, this application pertains to a compound of Formula (I’) that is a compound of Formula (Fb),R1OOCOH HO" -l-OHOr3(Fb), wherein R1, R3, R5, R6and R7are as defined herein.

[0670] In one aspect, this application pertains to a compound of Formula (F) that is a compound of Formula ( c),R3(FC), wherein R1, R3, R5, R6and R7are as defined herein.

[0671] In one aspect, this application pertains to a compound of Formula (F) that is a compound of Formula (I’d),r3(I’d), wherein R1, R3, R5, R6and R7are as defined herein.

[0672] In one aspect, this application pertains to a compound of Formula (F) that is a compound of Formula (I’e),(I’e), wherein R1, R3, R5, R6and R7are as defined herein.

[0673] In one aspect, this application pertains to a compound of Formula (I’) that is a compound of Formula (I’f),(I’f), wherein R1, R3, R5, R6and R7are as defined herein.

[0674] In one embodiment, the compound of Formula (I) is a compound of Formula (I’g),(Fg) wherein R1, R3, R5, R6, and R7are as defined herein.

[0675] In one embodiment, the compound of Formula (I) is a compound of Formula (I’h),R61ROOC^XPQ R7 / O^OAc AcO^°XX^|'°\AcO (Fh) wherein R1, R3, R5, R6, and R7are as defined herein.

[0676] In one embodiment, when X is O and R3is O(Ry), then Ryis not H.

[0677] In one embodiment, when X is O and R3is O(Ry), then Ryis Ci-Ce alkyl.

[0678] In one embodiment, when X is O and R3is O(Ry), then Ryis methyl.

[0679] In one embodiment, when X is O and R3is O(Ry), then Ryis ethyl.

[0680] In one embodiment, when X is O and R3is O(Ry), then Ryis n-propyl

[0681] In one embodiment, when X is O and R3is O(Ry), then Ryis iso-propyl

[0682] In one embodiment, when X is O and R3is O(Ry), then Ryis iso-butyl.

[0683] In one embodiment, when X is O and R3is O(Ry), then Ryis sec-butyl.

[0684] In one embodiment, when X is O and R3is O(Ry), then Ryis tert-butyl.

[0685] In one embodiment, when X is O and R3is O(Ry), then Ryis Cs alkyl.

[0686] In one embodiment, when X is O and R3is O(Ry), then Ryis Ce alkyl.

[0687] In one embodiment, when X is O and R3is O(Ry), then Ryis allyl.

[0688] In one embodiment, when X is O and R3is O(Ry), then Ryis propargyl.

[0689] In one embodiment, when X is O and R3is O(Ry), then Ry is Ci-Ce alkyl.

[0690] In one aspect, this application pertains to a compound of Formula (F), wherein the compound is:Compound ID No. Structure1CK. O1 H H OMjC- 1 / "^X^X " CH;I JL2 CH, 05 H H Ol IL / / ''QxyM 7 1 ' Il ) ®H3\ >~O Me C fA / / AM '» Vo HM—P-Oa-A OH HO^V+94O HN. P— oQ— \ OHHO^VM-GCMe5\~O Me 4 ff— \ itO HN—?-OC-A OHHfSS±^QMe5and 6}^ jy? J \* ° is rO HN"“;P"-C>L-X QHHO^AJ-qHO-^"OMe 5or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0691] In one embodiment, the compound of the present disclosure is Compound 1 or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0692] In one embodiment, the compound of the present disclosure is Compound 1 or a pharmaceutically acceptable salt thereof.

[0693] In one embodiment, the compound of the present disclosure is Compound 2 or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0694] In one embodiment, the compound of the present disclosure is Compound 2 or a pharmaceutically acceptable salt thereof.SYNTHESIS OF COMPOUNDS OF FORMULA (F)

[0695] The compounds of the application may be synthesized according to the methods established in the art. See, for example, Topics in Current Chemistry. Phosphorus Chemistry I. Asymmetric Synthesis and Bioactive Compounds. Jean-Luc Montchamp, Ed., Springer International Published, Switzerland, 2015, which is incorporated by reference in its entirety.)

[0696] In one embodiment, one or more intermediates in the preparation of the compounds of the present disclosure may be prepared by the schemes below:

[0697] In one embodiment, a compound of Formula (F) may be prepared according to the general and specific schemes below.

[0698] Starting material 1 is reacted under Grignard conditions with the mannoside 2 to form compound 3 and analogs thereof. A specific synthesis of one embodiment of the present disclosure is seen below.4 5 6

[0699] Intermediate isopropyl ((S)-(perfluorophenoxy)(phenoxy)phosphoryl)-L-alaninate (4) (Org. Lett. 2017, 19, 9, 2218-2221, which is incorporated by reference in its entirety) is reacted with the methyl a-D-mannopyranoside (5) to form compound 6 which can be further functionalized by reacting with an appropriate electrophile (acetyl bromide, acetoxymethyl bromide, acetic anhydride) and, optionally, a base (e.g., 4-dimethylaminopyridine) to provide various compound modifications.

[0700] In one embodiment, a compound of Formula (I’) may be prepared according to the following scheme:

[0701] In one embodiment, a compound of Formula (I’) may be prepared according to the following scheme:t5

[0702] In one aspect, this application pertains to a compound of Formula (I”):(I”), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:Xis CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;each R5is, independently, H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;each R7is, independently, H or C1-C3 alkyl;alternatively, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

[0703] In one embodiment, when X is C(Y1)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis H, C2-C6 alkyl, C2-C6 alkenyl, C4-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy.

[0704] In one embodiment, when X is C(YX)(Y2); Y1and Y2are each H; R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, or heteroaryl.

[0705] In one embodiment, X is C(Y1)(Y2).

[0706] In one embodiment, in the compound of Formula (I”), Y1and Y2are the same. For example, Y1and Y2are both H, Y1and Y2are both halo, or Y1and Y2are both Ci-Ce alkyl.

[0707] In one embodiment, Y1and Y2are both fluoro.

[0708] In one embodiment, Y1and Y2are methyl.

[0709] In one embodiment, in the compound of Formula (I”), Y1and Y2are the different.

[0710] In one embodiment, Y1is H and Y2is OH, halo, or Ci-Ce alkyl.

[0711] In one embodiment, Y1is H and Y2is OH. In one embodiment, Y1is H and Y2is halo. In one embodiment, Y1is H and Y2is Ci-Ce alkyl.

[0712] In one embodiment, X is C(=O).

[0713] In one embodiment, X is O.

[0714] In one embodiment, each R1is H.

[0715] In one embodiment, each of R1in the compound of Formula (I”) is the same. For example, each R1is H or each R1is Ci-Ce alkyl.

[0716] In one embodiment, each R1is H.

[0717] In one embodiment, each R1is Ci-Ce alkyl.

[0718] In one embodiment, each R1is methyl.

[0719] In one embodiment, each R1is ethyl.

[0720] In one embodiment, each R1is n-propyl.

[0721] In one embodiment, each R1is iso-propyl.

[0722] In one embodiment, each R1is iso-butyl.

[0723] In one embodiment, each R1is sec-butyl.

[0724] In one embodiment, each R1is tert-butyl.

[0725] In one embodiment, each R1is n-butyl.

[0726] In one embodiment, each R1is C5 alkyl.

[0727] In one embodiment, each R1is Ce alkyl.

[0728] In one embodiment, each R1is C2-C6 alkenyl.

[0729] In one embodiment, each R1is C2-C6 alkynyl.

[0730] In one embodiment, each R1is C3-C8cycloalkyl.

[0731] In one embodiment, each R1is heterocyclyl.

[0732] In one embodiment, each R1is aryl.

[0733] In one embodiment, each R1is heteroaryl.

[0734] In one embodiment, each R1is cholesteryl.

[0735] In one embodiment, each of R1in the compound of Formula (I”) is different. For example, one of R1is Ci-Ce alkyl and the other R1is a different Ci-Ce alkyl; or one of R1is Ci-Ce alkyl and the other R1is H, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl.

[0736] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is a different Ci-Ce alkyl.

[0737] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is H.

[0738] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C2-C6 alkenyl.

[0739] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C2-C6 alkynyl.

[0740] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C3-C8cycloalkyl.

[0741] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is heterocyclyl.

[0742] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is aryl.

[0743] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is heteroaryl.

[0744] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is cholesteryl.

[0745] In one embodiment, one of R1is methyl and the other R1is H.

[0746] In one embodiment, one of R1is methyl and the other R1is C2-C6 alkenyl.

[0747] In one embodiment, one of R1is methyl and the other R1is C2-C6 alkynyl.

[0748] In one embodiment, one of R1is methyl and the other R1is C3-C8cycloalkyl.

[0749] In one embodiment, one of R1is methyl and the other R1is heterocyclyl.

[0750] In one embodiment, one of R1is methyl and the other R1is aryl.

[0751] In one embodiment, one of R1is methyl and the other R1is heteroaryl.

[0752] In one embodiment, one of R1is methyl and the other R1is cholesteryl.

[0753] In one embodiment, one of R1is ethyl and the other R1is H.

[0754] In one embodiment, one of R1is ethyl and the other R1is C2-C6 alkenyl.

[0755] In one embodiment, one of R1is ethyl and the other R1is C2-C6 alkynyl.

[0756] In one embodiment, one of R1is ethyl and the other R1is C3-C8cycloalkyl.

[0757] In one embodiment, one of R1is ethyl and the other R1is heterocyclyl.

[0758] In one embodiment, one of R1is ethyl and the other R1is aryl.

[0759] In one embodiment, one of R1is ethyl and the other R1is heteroaryl.

[0760] In one embodiment, one of R1is ethyl and the other R1is cholesteryl.

[0761] In one embodiment, one of R1is n-propyl and the other R1is H.

[0762] In one embodiment, one of R1is n-propyl and the other R1is C2-C6 alkenyl.

[0763] In one embodiment, one of R1is n-propyl and the other R1is C2-C6 alkynyl.

[0764] In one embodiment, one of R1is n-propyl and the other R1is C3-C8cycloalkyl.

[0765] In one embodiment, one of R1is n-propyl and the other R1is heterocyclyl.

[0766] In one embodiment, one of R1is n-propyl and the other R1is aryl.

[0767] In one embodiment, one of R1is n-propyl and the other R1is heteroaryl.

[0768] In one embodiment, one of R1is n-propyl and the other R1is cholesteryl.

[0769] In one embodiment, one of R1is iso-propyl and the other R1is H.

[0770] In one embodiment, one of R1is iso-propyl and the other R1is C2-C6 alkenyl.

[0771] In one embodiment, one of R1is iso-propyl and the other R1is C2-C6 alkynyl.

[0772] In one embodiment, one of R1is iso-propyl and the other R1is C3-C8cycloalkyl.

[0773] In one embodiment, one of R1is iso-propyl and the other R1is heterocyclyl.

[0774] In one embodiment, one of R1is iso-propyl and the other R1is aryl.

[0775] In one embodiment, one of R1is iso-propyl and the other R1is heteroaryl.

[0776] In one embodiment, one of R1is iso-propyl and the other R1is cholesteryl.

[0777] In one embodiment, one of R1is n-butyl and the other R1is H.

[0778] In one embodiment, one of R1is n-butyl and the other R1is C2-C6 alkenyl.

[0779] In one embodiment, one of R1is n-butyl and the other R1is C2-C6 alkynyl.

[0780] In one embodiment, one of R1is n-butyl and the other R1is C3-C8cycloalkyl.

[0781] In one embodiment, one of R1is n-butyl and the other R1is heterocyclyl.

[0782] In one embodiment, one of R1is n-butyl and the other R1is aryl.

[0783] In one embodiment, one of R1is n-butyl and the other R1is heteroaryl.

[0784] In one embodiment, one of R1is n-butyl and the other R1is cholesteryl.

[0785] In one embodiment, one of R1is iso-butyl and the other R1is H.

[0786] In one embodiment, one of R1is iso-butyl and the other R1is C2-C6 alkenyl.

[0787] In one embodiment, one of R1is iso-butyl and the other R1is C2-C6 alkynyl.

[0788] In one embodiment, one of R1is iso-butyl and the other R1is C3-C8cycloalkyl.

[0789] In one embodiment, one of R1is iso-butyl and the other R1is heterocyclyl.

[0790] In one embodiment, one of R1is iso-butyl and the other R1is aryl.

[0791] In one embodiment, one of R1is iso-butyl and the other R1is heteroaryl.

[0792] In one embodiment, one of R1is iso-butyl and the other R1is cholesteryl.

[0793] In one embodiment, one of R1is sec-butyl and the other R1is H.

[0794] In one embodiment, one of R1is sec-butyl and the other R1is C2-C6 alkenyl.

[0795] In one embodiment, one of R1is sec-butyl and the other R1is C2-C6 alkynyl.

[0796] In one embodiment, one of R1is sec-butyl and the other R1is C3-C8cycloalkyl.

[0797] In one embodiment, one of R1is sec-butyl and the other R1is heterocyclyl.

[0798] In one embodiment, one of R1is sec-butyl and the other R1is aryl.

[0799] In one embodiment, one of R1is sec-butyl and the other R1is heteroaryl.

[0800] In one embodiment, one of R1is sec-butyl and the other R1is cholesteryl.

[0801] In one embodiment, one of R1is tert-butyl and the other R1is H.

[0802] In one embodiment, one of R1is tert-butyl and the other R1is C2-C6 alkenyl.

[0803] In one embodiment, one of R1is tert-butyl and the other R1is C2-C6 alkynyl.

[0804] In one embodiment, one of R1is tert-butyl and the other R1is C3-C8cycloalkyl.

[0805] In one embodiment, one of R1is tert-butyl and the other R1is heterocyclyl.

[0806] In one embodiment, one of R1is tert-butyl and the other R1is aryl.

[0807] In one embodiment, one of R1is tert-butyl and the other R1is heteroaryl.

[0808] In one embodiment, one of R1is tert-butyl and the other R1is cholesteryl.

[0809] In one embodiment, one of R1is C5 alkyl and the other R1is H.

[0810] In one embodiment, one of R1is C5 alkyl and the other R1is C2-C6 alkenyl.

[0811] In one embodiment, one of R1is C5 alkyl and the other R1is C2-C6 alkynyl.

[0812] In one embodiment, one of R1is C5 alkyl and the other R1is C3-C8cycloalkyl.

[0813] In one embodiment, one of R1is C5 alkyl and the other R1is heterocyclyl.

[0814] In one embodiment, one of R1is C5 alkyl and the other R1is aryl.

[0815] In one embodiment, one of R1is C5 alkyl and the other R1is heteroaryl.

[0816] In one embodiment, one of R1is C5 alkyl and the other R1is cholesteryl.

[0817] In one embodiment, one of R1is Ce alkyl and the other R1is H.

[0818] In one embodiment, one of R1is Ce alkyl and the other R1is C2-C6 alkenyl.

[0819] In one embodiment, one of R1is Ce alkyl and the other R1is C2-C6 alkynyl.

[0820] In one embodiment, one of R1is Ce alkyl and the other R1is C3-C8cycloalkyl.

[0821] In one embodiment, one of R1is Ce alkyl and the other R1is heterocyclyl.

[0822] In one embodiment, one of R1is Ce alkyl and the other R1is aryl.

[0823] In one embodiment, one of R1is Ce alkyl and the other R1is heteroaryl.

[0824] In one embodiment, one of R1is Ce alkyl and the other R1is cholesteryl.

[0825] In one embodiment, each of R2in the compound of Formula (I”) is the same. For example, each R2is H or each R2is -(CH2)m-Z-C(=O)-Rx.

[0826] In one embodiment, each R2is H.

[0827] In one embodiment, each R2is Ci-Ce alkyl.

[0828] In one embodiment, each R2is C2-C6 alkenyl.

[0829] In one embodiment, each R2is C2-C6 alkynyl.

[0830] In one embodiment, each R2is C3-C8cycloalkyl.

[0831] In one embodiment, each R2is heterocyclyl.

[0832] In one embodiment, each R2is aryl.

[0833] In one embodiment, each R2is heteroaryl.

[0834] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis H.

[0835] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis Ci-Ce alkyl.

[0836] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkenyl.

[0837] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkynyl.

[0838] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C3-C8cycloalkyl.

[0839] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heterocyclyl.

[0840] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis aryl.

[0841] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heteroaryl.

[0842] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 0.

[0843] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 1.

[0844] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 2.

[0845] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 3.

[0846] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 4.

[0847] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 5.

[0848] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 6.

[0849] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 7.

[0850] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 8.

[0851] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 9.

[0852] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 10.

[0853] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 0, and Z is absent.

[0854] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is absent.

[0855] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is O.

[0856] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is absent.

[0857] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is O.

[0858] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is absent.

[0859] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is O.

[0860] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is absent.

[0861] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is O.

[0862] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is absent.

[0863] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is O.

[0864] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is absent.

[0865] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is O.

[0866] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is absent.

[0867] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is O.

[0868] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is absent.

[0869] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is O.

[0870] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is absent.

[0871] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is O.

[0872] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is absent.

[0873] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is O.

[0874] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent.

[0875] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is absent.

[0876] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O.

[0877] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is absent.

[0878] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is O.

[0879] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is absent.

[0880] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is O.

[0881] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is absent.

[0882] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is O.

[0883] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is absent.

[0884] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is O.

[0885] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is absent.

[0886] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is O.

[0887] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is absent.

[0888] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is O.

[0889] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is absent.

[0890] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is O.

[0891] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is absent.

[0892] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is O.

[0893] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is absent.

[0894] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is O.

[0895] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 0, and Z is absent.

[0896] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is absent.

[0897] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is O.

[0898] In one embodiment, two of R2in the compound of Formula (I”) are the same and the other R2is different. For example, two of R2is H or the other R2is -(CH2)m-Z-C(=O)-Rx; or two of R2is -(CH2)m-Z-C(=O)-Rxor the other R2is H.

[0899] In one embodiment, all three of R2in the compound of Formula (I”) are different. For example, one of R2is H, one of R2is -(CH2)m-Z-C(=O)-Rx, and the other R2is Ci-Ce alkyl.

[0900] In one embodiment, Rxis H.

[0901] In one embodiment, Rxis Ci-Ce alkyl.

[0902] In one embodiment, Rxis methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, tertbutyl, Cs alkyl, or Ce alkyl.

[0903] In one embodiment, Rxis C2-C6 alkenyl.

[0904] In one embodiment, Rxis C2-C6 alkynyl.

[0905] In one embodiment, Rxis C3-C8cycloalkyl.

[0906] In one embodiment, Rxis heterocyclyl.

[0907] In one embodiment, Rxis aryl.

[0908] In one embodiment, Rxis heteroaryl.

[0909] In one embodiment, in the compound of Formula (I”), R3is H.

[0910] In one embodiment, R3is Ci-Ce alkyl.

[0911] In one embodiment, R3is methyl.

[0912] In one embodiment, R3is ethyl.

[0913] In one embodiment, R3is n-propyl

[0914] In one embodiment, R3is iso-propyl

[0915] In one embodiment, R3is iso-butyl.

[0916] In one embodiment, R3is sec-butyl

[0917] In one embodiment, R3is tert-butyl

[0918] In one embodiment, R3is C5 alkyl.

[0919] In one embodiment, R3is Ce alkyl.

[0920] In one embodiment, R3is C2-C6 alkenyl,

[0921] In one embodiment, R3is C2-C6 alkynyl.

[0922] In one embodiment, R3is C3-C8cycloalkyl.

[0923] In one embodiment, R3is heterocyclyl.

[0924] In one embodiment, R3is aryl.

[0925] In one embodiment, R3is heteroaryl.

[0926] In one embodiment, R3is O(Ry).

[0927] In one embodiment, R3is N(Ry)2.

[0928] In one embodiment, R3is SRy.

[0929] In one embodiment, R3is S(=O)nRy.

[0930] In one embodiment, each of R5in the compound of Formula (I”) is the same. For example, each R5is H or each R5is Ci-Ce alkyl.

[0931] In one embodiment, each R5is H.

[0932] In one embodiment, each R5is Ci-Ce alkyl.

[0933] In one embodiment, each R5is Ci-Ce alkyl, substituted by one or more R.

[0934] In one embodiment, each R5is methyl.

[0935] In one embodiment, each R5is methyl, substituted by one or more R.

[0936] In one embodiment, each R5is ethyl.

[0937] In one embodiment, each R5is ethyl, substituted by one or more R.

[0938] In one embodiment, each R5is n-propyl

[0939] In one embodiment, each R5is iso-propyl

[0940] In one embodiment, each R5is iso-butyl.

[0941] In one embodiment, each R5is sec-butyl

[0942] In one embodiment, each R5is tert-butyl

[0943] In one embodiment, each R5is Cs alkyl.

[0944] In one embodiment, each R5is Ce alkyl.

[0945] In one embodiment, each R5is an amino acid side chain.

[0946] In one embodiment, each R5is -CH2-NH2.

[0947] In one embodiment, each R5is -CH2-OH.

[0948] In one embodiment, each R5is -CH(-OH)-CH3.

[0949] In one embodiment, each R5is -CH2-C(=O)-NH2.

[0950] In one embodiment, each R5is -(CH2)2-C(=O)-NH2.

[0951] In one embodiment, each R5is -CH2-COOH.

[0952] In one embodiment, each R5is -(CH2)2-COOH.

[0953] In one embodiment, each R5is -CH2-SH.

[0954] In one embodiment, each R5is -CH2-S-CH3.

[0955] In one embodiment, each R5is -(CH2)2-SH.

[0956] In one embodiment, each R5is -(CH2)2-S-CH3.

[0957] In one embodiment, each R5is -(CH2)2-NH-C(=NH)-NH2.

[0958] In one embodiment, each R5is -(CH2)3-NH-C(=NH)-NH2.

[0959] In one embodiment, each R5is -(CH2)4-NH-C(=NH)-NH2.

[0960] In one embodiment, each R5is -(CH2)4-NH2.

[0961] In one embodiment, each R5is -CH2-phenyl.

[0962] In one embodiment, each R5is -CH2-phenyl substituted by OH.

[0963] In one embodiment, each R5is -CH2-phenyl substituted by para-OH.

[0964] In one embodiment, each R5is -CH2-heteroaryl.

[0965] In one embodiment, each R5is -CH2-imidazolyl.

[0966] In one embodiment, each R5is -CH2-heterocyclyl.

[0967] In one embodiment, each R5is -CH2-indolyl.

[0968] In one embodiment, each R5is heterocyclyl.

[0969] In one embodiment, each R5is aryl.

[0970] In one embodiment, each R5is heteroaryl.

[0971] In one embodiment, each of R5in the compound of Formula (I”) is different. For example, one of R5is Ci-Ce alkyl and the other R5is a different Ci-Ce alkyl; or one of R5is Ci-Ce alkyl and the other R5is H, heterocyclyl, aryl, or heteroaryl.

[0972] In one embodiment, one of R5is Ci-Ce alkyl and the other R5is H.

[0973] In one embodiment, one of R5is Ci-Ce alkyl and the other R5is heterocyclyl.

[0974] In one embodiment, one of R5is Ci-Ce alkyl and the other R5is aryl.

[0975] In one embodiment, one of R5is Ci-Ce alkyl and the other R5is heteroaryl.

[0976] In one embodiment, one of R5is methyl and the other R5is H.

[0977] In one embodiment, one of R5is methyl and the other R5is heterocyclyl.

[0978] In one embodiment, one of R5is methyl and the other R5is aryl.

[0979] In one embodiment, one of R5is methyl and the other R5is heteroaryl.

[0980] In one embodiment, one of R5is ethyl and the other R5is H.

[0981] In one embodiment, one of R5is ethyl and the other R5is heterocyclyl.

[0982] In one embodiment, one of R5is ethyl and the other R5is aryl.

[0983] In one embodiment, one of R5is ethyl and the other R5is heteroaryl.

[0984] In one embodiment, one of R5is n-propyl and the other R5is H.

[0985] In one embodiment, one of R5is n-propyl and the other R5is heterocyclyl.

[0986] In one embodiment, one of R5is n-propyl and the other R5is aryl.

[0987] In one embodiment, one of R5is n-propyl and the other R5is heteroaryl.

[0988] In one embodiment, one of R5is iso-propyl and the other R5is H.

[0989] In one embodiment, one of R5is iso-propyl and the other R5is heterocyclyl.

[0990] In one embodiment, one of R5is iso-propyl and the other R5is aryl.

[0991] In one embodiment, one of R5is iso-propyl and the other R5is heteroaryl.

[0992] In one embodiment, one of R5is H, and the other R5is -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0993] In one embodiment, one of R5is methyl, and the other R5is -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0994] In one embodiment, one of R5is ethyl, and the other R5is -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0995] In one embodiment, one of R5is n-propyl, and the other R5is -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0996] In one embodiment, one of R5is iso-propyl, and the other R5is -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CH2-imidazolyl, or -CH2-indolyl.

[0997] In one embodiment, each of R7in the compound of Formula (I”) is the same. For example, each R7is H or each R7is C1-C3 alkyl.

[0998] In one embodiment, each R7is H.

[0999] In one embodiment, each R7is C1-C3 alkyl.

[1000] In one embodiment, each R7is methyl.

[1001] In one embodiment, each R7is ethyl.

[1002] In one embodiment, each R7is n-propyl

[1003] In one embodiment, each R7is iso-propyl

[1004] In one embodiment, each of R7in the compound of Formula (I”) is different. For example, one of R7is C1-C3 alkyl and the other R7is a different C1-C3 alkyl; or one of R7is Ci-C3 alkyl and the other R7is H.

[1005] In one embodiment, one of R7is methyl and the other R7is H.

[1006] In one embodiment, one of R7is ethyl and the other R7is H.

[1007] In one embodiment, one of R7is n-propyl and the other R7is H.

[1008] In one embodiment, one of R7is iso-propyl and the other R7is H.

[1009] In one embodiment, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring.

[1010] In one embodiment, R5and R7, together with the adjacent atoms they are attached to, form a pyrrolidine.

[1011] In one embodiment, R5and R7, together with the adjacent atoms they are attached to, form a pyrrolidine that is only substituted by the -COOR1moiety.

[1012] In one embodiment, R5and R7, together with the adjacent atoms they are attached to, form a pyrrolidine that substituted by one or more R in addition to being substituted by the -COOR1moiety, wherein each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, C3-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH, or SH.

[1013] In one embodiment, each Ryis, independently, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[1014] In one embodiment, Ryis Ci-Ce alkyl.

[1015] In one embodiment, Ryis methyl.

[1016] In one embodiment, Ryis ethyl.

[1017] In one embodiment, Ryis n-propyl

[1018] In one embodiment, Ryis iso-propyl

[1019] In one embodiment, Ryis iso-butyl.

[1020] In one embodiment, Ryis sec-butyl.

[1021] In one embodiment, Ryis tert-butyl.

[1022] In one embodiment, Ryis Cs alkyl.

[1023] In one embodiment, Ryis Ce alkyl.

[1024] In one embodiment, Ryis allyl.

[1025] In one embodiment, Ryis propargyl.

[1026] In one embodiment, Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein each is substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[1027] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[1028] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein one R is hydrogen, and the other R isR, wherein R is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl; and X' is a counterion selected from the group consisting of fluoride, chloride, bromide, iodide, tritiate, and tosylate.

[1029] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1030] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is H.

[1031] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1032] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is H.

[1033] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1034] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1035] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1036] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is H.

[1037] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1038] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is H.

[1039] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1040] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl); andeach R7is H.

[1041] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1042] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1043] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1044] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1045] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-C6alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1046] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is — O(C2-Ce alkynyl); andeach R7is H.

[1047] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1048] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is H.

[1049] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1050] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is H.

[1051] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1052] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1053] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1054] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-C6 alkynyl); andeach R7is H.

[1055] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1056] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is H.

[1057] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is H.

[1058] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl); andeach R7is H.

[1059] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1060] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1061] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1062] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1063] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is H.

[1064] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is H.

[1065] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1066] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is - O(C2-Ce alkynyl); andeach R7is methyl.

[1067] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1068] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is — O(C2-Ce alkynyl); andeach R7is methyl.

[1069] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1070] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1071] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1072] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1073] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1074] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is — O(C2-Ce alkynyl); andeach R7is methyl.

[1075] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1076] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1077] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1078] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1079] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1080] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1081] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1082] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1083] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1084] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1085] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1086] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1087] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1088] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1089] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1090] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1091] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1092] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1093] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is methyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1094] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl); andeach R7is methyl.

[1095] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1096] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is methyl.

[1097] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1098] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is methyl.

[1099] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4 alkyl); andeach R7is methyl.

[1100] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl); andeach R7is methyl.[HOI] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1102] In one aspect, this application pertains to a compound of Formula (I”), wherein: X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is — O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1103] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1104] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1105] In one aspect, this application pertains to a compound of Formula (I”), wherein:Xis O;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1106] In one aspect, this application pertains to a compound of Formula (I”), wherein:Xis O;each R1is C1-C4 alkyl;each R2is H;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1107] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1108] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1109] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1110] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1111] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1112] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1113] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1114] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1115] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1116] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - 0(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1117] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1118] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1119] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1120] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1121] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1122] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is — O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1123] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1124] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1125] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1126] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1127] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1128] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1129] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1130] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1131] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1132] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1133] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1134] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1135] In one aspect, this application pertains to a compound of Formula (I”), wherein:Xis O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is H.

[1136] In one aspect, this application pertains to a compound of Formula (I”), wherein: X is O;each R1is H;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is H.

[1137] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1138] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1139] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1140] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1141] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1142] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is H;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1143] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1144] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-C6 alkynyl);each R5is methyl; andeach R7is methyl.

[1145] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1146] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is — O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1147] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1148] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1149] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1150] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - 0(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1051] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1052] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1153] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1054] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - OfCb-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1155] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1156] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is H;R3is — O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1157] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1158] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is H;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1059] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1160] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is H;R3is - 0(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1061] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1162] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1163] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1164] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1165] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is methyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1166] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1067] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1168] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is - O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1169] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1170] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is — O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1071] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(Ci-C4alkyl);each R5is methyl; andeach R7is methyl.

[1172] In one aspect, this application pertains to a compound of Formula (I”), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O;R3is -O(C2-Ce alkynyl);each R5is methyl; andeach R7is methyl.

[1173] In one aspect, this application pertains to a compound of Formula (I”) that is a compound of Formula (I”a),COOR15N-R7R5IN OH HO^ -1-0HOR'(I”a), wherein R1, R3, R5, and R7are as defined herein.

[1074] In one aspect, this application pertains to a compound of Formula (I”) that is a compound of Formula (I”b),(I”b), wherein R1, R3, R5, and R7are as defined herein.

[1175] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”c),(I”c), wherein R1, R3, R5, and R7are as defined herein.

[1076] In one embodiment, the compound of Formula (I”) is a compound of Formula (I”d),R51ROOC-<\R7XN'p"°1ROOC^N^PVQR7 / O^OAcAcO^O^M'°\^oA^--J'At|AcOR(I”d), wherein R1, R3, R5, and R7are as defined herein.

[1177] In one aspect, this application is directed to a compound of the following formula,(Compound Bl),or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1178] In one aspect, this application is directed to a compound of the following formula,(Compound Bl),or a pharmaceutically acceptable salt thereof.SYNTHESIS OF COMPOUNDS OF FORMULA (I”)

[1179] The compounds of the application may be synthesized according to the methods established in the art. See, for example, Topics in Current Chemistry. Phosphorus Chemistry I. Asymmetric Synthesis and Bioactive Compounds. Jean-Luc Montchamp, Ed., Springer International Published, Switzerland, 2015, which is incorporated by reference in its entirety.)

[1180] In one embodiment, one or more intermediates in the preparation of the compounds of the present disclosure may be prepared by the schemes below:

[1181] In one embodiment, a compound of Formula (I”) may be prepared according to the scheme below.1. EtsN (1 1 eq). POCI3(1 1 eq), THE-78 ' C to rt 2. L-aianine isopropyi ester HC! salt (5 eq), Et3N (10 eq) HO OH CH2Cl2. -78 °C to rt

[1182] The mannoside 1 is reacted with a phosphorus oxychloride to install the phosphorous center in the mannoside. A reactive amine, L-alanine isopropyl ester in the reaction illustrated above, is added to the reaction to form compound 2 which can be further functionalized by reacting with an appropriate electrophile (acetyl bromide, acetoxymethyl bromide, acetic anhydride) and, optionally, a base (e.g., 4-dimethylaminopyridine) to provide various compound modifications.

[1183] In one embodiment, a compound of Formula (F) may be prepared according to the following scheme:

[1184] In one aspect, this application pertains to a compound of Formula (I),(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=0)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2,provided that:when X is C(YX)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis not methyl or propargyl; andwhen X is C(YX)(Y2); Y1and Y2are each H; each R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis not 2,4-dimethylphenyl.

[1185] In one embodiment, when X is C(YX)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis H, C2-C6 alkyl, C2-C6 alkenyl, C4-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy.

[1186] In one embodiment, when X is C(YX)(Y2); Y1and Y2are each H; each R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, or heteroaryl.

[1187] In one embodiment, X is C(Y1)(Y2).

[1188] In one embodiment, in the compound of Formula (I), Y1and Y2are the same. For example, Y1and Y2are both H, Y1and Y2are both halo, or Y1and Y2are both Ci-Ce alkyl.

[1189] In one embodiment, Y1and Y2are both fluoro.

[1190] In one embodiment, Y1and Y2are methyl.

[1091] In one embodiment, in the compound of Formula (I), Y1and Y2are the different.

[1192] In one embodiment, Y1is H and Y2is OH, halo, or Ci-Ce alkyl.

[1193] In one embodiment, Y1is H and Y2is OH. In one embodiment, Y1is H and Y2is halo. In one embodiment, Y1is H and Y2is Ci-Ce alkyl.

[1194] In one embodiment, X is C(=O).

[1095] In one embodiment, X is O.

[1196] In one embodiment, each of R1in the compound of Formula (I) is the same. For example, each R1is H or each R1is Ci-Ce alkyl.

[1197] In one embodiment, each R1is H.

[1198] In one embodiment, each R1is Ci-Ce alkyl.

[1199] In one embodiment, each R1is methyl.

[1200] In one embodiment, each R1is ethyl.

[1201] In one embodiment, each R1is n-propyl.

[1202] In one embodiment, each R1is iso-propyl.

[1203] In one embodiment, each R1is iso-butyl.

[1204] In one embodiment, each R1is sec-butyl.

[1205] In one embodiment, each R1is tert-butyl.

[1206] In one embodiment, each R1is n-butyl.

[1207] In one embodiment, each R1is Cs alkyl.

[1208] In one embodiment, each R1is Ce alkyl.

[1209] In one embodiment, each R1is C2-C6 alkenyl.

[1210] In one embodiment, each R1is C2-C6 alkynyl.

[1211] In one embodiment, each R1is C3-C8cycloalkyl.

[1212] In one embodiment, each R1is heterocyclyl.

[1213] In one embodiment, each R1is aryl.

[1214] In one embodiment, each R1is heteroaryl.

[1215] In one embodiment, each R1is cholesteryl.

[1216] In one embodiment, each of R1in the compound of Formula (I) is different. For example, one of R1is Ci-Ce alkyl and the other R1is a different Ci-Ce alkyl; or one of R1is Ci-Ce alkyl and the other R1is H, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl.

[1217] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is a different Ci-Ce alkyl.

[1218] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is H.

[1219] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C2-C6 alkenyl.

[1220] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C2-C6 alkynyl.

[1221] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is C3-C8cycloalkyl.

[1222] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is heterocyclyl.

[1223] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is aryl.

[1224] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is heteroaryl.

[1225] In one embodiment, one of R1is Ci-Ce alkyl and the other R1is cholesteryl.

[1226] In one embodiment, one of R1is methyl and the other R1is H.

[1227] In one embodiment, one of R1is methyl and the other R1is C2-C6 alkenyl.

[1228] In one embodiment, one of R1is methyl and the other R1is C2-C6 alkynyl.

[1229] In one embodiment, one of R1is methyl and the other R1is C3-C8cycloalkyl.

[1230] In one embodiment, one of R1is methyl and the other R1is heterocyclyl.

[1231] In one embodiment, one of R1is methyl and the other R1is aryl.

[1232] In one embodiment, one of R1is methyl and the other R1is heteroaryl.

[1233] In one embodiment, one of R1is methyl and the other R1is cholesteryl.

[1234] In one embodiment, one of R1is ethyl and the other R1is H.

[1235] In one embodiment, one of R1is ethyl and the other R1is C2-C6 alkenyl.

[1236] In one embodiment, one of R1is ethyl and the other R1is C2-C6 alkynyl.

[1237] In one embodiment, one of R1is ethyl and the other R1is C3-C8cycloalkyl.

[1238] In one embodiment, one of R1is ethyl and the other R1is heterocyclyl.

[1239] In one embodiment, one of R1is ethyl and the other R1is aryl.

[1240] In one embodiment, one of R1is ethyl and the other R1is heteroaryl.

[1241] In one embodiment, one of R1is ethyl and the other R1is cholesteryl.

[1242] In one embodiment, one of R1is n-propyl and the other R1is H.

[1243] In one embodiment, one of R1is n-propyl and the other R1is C2-C6 alkenyl.

[1244] In one embodiment, one of R1is n-propyl and the other R1is C2-C6 alkynyl.

[1245] In one embodiment, one of R1is n-propyl and the other R1is C3-C8cycloalkyl.

[1246] In one embodiment, one of R1is n-propyl and the other R1is heterocyclyl.

[1247] In one embodiment, one of R1is n-propyl and the other R1is aryl.

[1248] In one embodiment, one of R1is n-propyl and the other R1is heteroaryl.

[1249] In one embodiment, one of R1is n-propyl and the other R1is cholesteryl.

[1250] In one embodiment, one of R1is iso-propyl and the other R1is H.

[1251] In one embodiment, one of R1is iso-propyl and the other R1is C2-C6 alkenyl.

[1252] In one embodiment, one of R1is iso-propyl and the other R1is C2-C6 alkynyl.

[1253] In one embodiment, one of R1is iso-propyl and the other R1is C3-C8cycloalkyl.

[1254] In one embodiment, one of R1is iso-propyl and the other R1is heterocyclyl.

[1255] In one embodiment, one of R1is iso-propyl and the other R1is aryl.

[1256] In one embodiment, one of R1is iso-propyl and the other R1is heteroaryl.

[1257] In one embodiment, one of R1is iso-propyl and the other R1is cholesteryl.

[1258] In one embodiment, one of R1is n-butyl and the other R1is H.

[1259] In one embodiment, one of R1is n-butyl and the other R1is C2-C6 alkenyl.

[1260] In one embodiment, one of R1is n-butyl and the other R1is C2-C6 alkynyl.

[1261] In one embodiment, one of R1is n-butyl and the other R1is C3-C8cycloalkyl.

[1262] In one embodiment, one of R1is n-butyl and the other R1is heterocyclyl.

[1263] In one embodiment, one of R1is n-butyl and the other R1is aryl.

[1264] In one embodiment, one of R1is n-butyl and the other R1is heteroaryl.

[1265] In one embodiment, one of R1is n-butyl and the other R1is cholesteryl.

[1266] In one embodiment, one of R1is iso-butyl and the other R1is H.

[1267] In one embodiment, one of R1is iso-butyl and the other R1is C2-C6 alkenyl.

[1268] In one embodiment, one of R1is iso-butyl and the other R1is C2-C6 alkynyl.

[1269] In one embodiment, one of R1is iso-butyl and the other R1is C3-C8cycloalkyl.

[1270] In one embodiment, one of R1is iso-butyl and the other R1is heterocyclyl.

[1271] In one embodiment, one of R1is iso-butyl and the other R1is aryl.

[1272] In one embodiment, one of R1is iso-butyl and the other R1is heteroaryl.

[1273] In one embodiment, one of R1is iso-butyl and the other R1is cholesteryl.

[1274] In one embodiment, one of R1is sec-butyl and the other R1is H.

[1275] In one embodiment, one of R1is sec-butyl and the other R1is C2-C6 alkenyl.

[1276] In one embodiment, one of R1is sec-butyl and the other R1is C2-C6 alkynyl.

[1277] In one embodiment, one of R1is sec-butyl and the other R1is C3-C8cycloalkyl.

[1278] In one embodiment, one of R1is sec-butyl and the other R1is heterocyclyl.

[1279] In one embodiment, one of R1is sec-butyl and the other R1is aryl.

[1280] In one embodiment, one of R1is sec-butyl and the other R1is heteroaryl.

[1281] In one embodiment, one of R1is sec-butyl and the other R1is cholesteryl.

[1282] In one embodiment, one of R1is tert-butyl and the other R1is H.

[1283] In one embodiment, one of R1is tert-butyl and the other R1is C2-C6 alkenyl.

[1284] In one embodiment, one of R1is tert-butyl and the other R1is C2-C6 alkynyl.

[1285] In one embodiment, one of R1is tert-butyl and the other R1is C3-C8cycloalkyl.

[1286] In one embodiment, one of R1is tert-butyl and the other R1is heterocyclyl.

[1287] In one embodiment, one of R1is tert-butyl and the other R1is aryl.

[1288] In one embodiment, one of R1is tert-butyl and the other R1is heteroaryl.

[1289] In one embodiment, one of R1is tert-butyl and the other R1is cholesteryl.

[1290] In one embodiment, one of R1is Cs alkyl and the other R1is H.

[1291] In one embodiment, one of R1is Cs alkyl and the other R1is C2-C6 alkenyl.

[1292] In one embodiment, one of R1is C5 alkyl and the other R1is C2-C6 alkynyl.

[1293] In one embodiment, one of R1is C5 alkyl and the other R1is C3-C8cycloalkyl.

[1294] In one embodiment, one of R1is C5 alkyl and the other R1is heterocyclyl.

[1295] In one embodiment, one of R1is C5 alkyl and the other R1is aryl.

[1296] In one embodiment, one of R1is C5 alkyl and the other R1is heteroaryl.

[1297] In one embodiment, one of R1is C5 alkyl and the other R1is cholesteryl.

[1298] In one embodiment, one of R1is Ce alkyl and the other R1is H.

[1299] In one embodiment, one of R1is Ce alkyl and the other R1is C2-C6 alkenyl.

[1300] In one embodiment, one of R1is Ce alkyl and the other R1is C2-C6 alkynyl.

[1301] In one embodiment, one of R1is Ce alkyl and the other R1is C3-C8cycloalkyl.

[1302] In one embodiment, one of R1is Ce alkyl and the other R1is heterocyclyl.

[1303] In one embodiment, one of R1is Ce alkyl and the other R1is aryl.

[1304] In one embodiment, one of R1is Ce alkyl and the other R1is heteroaryl.

[1305] In one embodiment, one of R1is Ce alkyl and the other R1is cholesteryl.

[1306] In one embodiment, each of R2in the compound of Formula (I) is the same. For example, each R2is H or each R2is -(CH2)m-Z-C(=O)-Rx.

[1307] In one embodiment, each R2is H.

[1308] In one embodiment, each R2is Ci-Ce alkyl.

[1309] In one embodiment, each R2is C2-C6 alkenyl.

[1310] In one embodiment, each R2is C2-C6 alkynyl.

[1311] In one embodiment, each R2is C3-C8cycloalkyl.

[1312] In one embodiment, each R2is heterocyclyl.

[1313] In one embodiment, each R2is aryl.

[1314] In one embodiment, each R2is heteroaryl.

[1315] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis H.

[1316] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis Ci-Ce alkyl.

[1317] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkenyl.

[1318] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis C2-C6 alkynyl.

[1319] In one embodiment, each R2is -(CH2)m-Z-C(=0)-Rxand Rxis C3-C8cycloalkyl.

[1320] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heterocyclyl.

[1321] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis aryl.

[1322] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand Rxis heteroaryl.

[1323] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 0.

[1324] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 1.

[1325] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 2.

[1326] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 3.

[1327] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 4.

[1328] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 5.

[1329] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 6.

[1330] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 7.

[1331] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 8.

[1332] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 9.

[1333] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rxand m is 10.

[1334] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 0, and Z is absent.

[1335] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is absent.

[1336] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 1, and Z is O.

[1337] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is absent.

[1338] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 2, and Z is O.

[1339] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is absent.

[1340] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 3, and Z is O.

[1341] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is absent.

[1342] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 4, and Z is O.

[1343] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is absent.

[1344] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 5, and Z is O.

[1345] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is absent.

[1346] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 6, and Z is O.

[1347] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is absent.

[1348] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 7, and Z is O.

[1349] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is absent.

[1350] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 8, and Z is O.

[1351] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is absent.

[1352] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 9, and Z is O.

[1353] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is absent.

[1354] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, m is 10, and Z is O.

[1355] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent.

[1356] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is absent.

[1357] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O.

[1358] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is absent.

[1359] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 2, and Z is O.

[1360] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is absent.

[1361] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 3, and Z is O.

[1362] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is absent.

[1363] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 4, and Z is O.

[1364] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is absent.

[1365] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 5, and Z is O.

[1366] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is absent.

[1367] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 6, and Z is O.

[1368] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is absent.

[1369] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 7, and Z is O.

[1370] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is absent.

[1371] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 8, and Z is O.

[1372] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is absent.

[1373] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 9, and Z is O.

[1374] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is absent.

[1375] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 10, and Z is O.

[1376] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 0, and Z is absent.

[1377] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is absent.

[1378] In one embodiment, each R2is -(CH2)m-Z-C(=O)-Rx, Rxis methyl, m is 1, and Z is O.

[1379] In one embodiment, two of R2in the compound of Formula are the same and the other R2is different. For example, two of R2is H or the other R2is -(CH2)m-Z-C(=O)-Rx; or two of R2is -(CH2)m-Z-C(=O)-Rxor the other R2is H.

[1380] In one embodiment, all three of R2in the compound of Formula (I) are different. For example, one of R2is H, one of R2is -(CH2)m-Z-C(=O)-Rx, and the other R2is Ci-Ce alkyl.

[1381] In one embodiment, Rxis H.

[1382] In one embodiment, Rxis Ci-Ce alkyl.

[1383] In one embodiment, Rxis methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, tertbutyl, Cs alkyl, or Ce alkyl.

[1384] In one embodiment, Rxis C2-C6 alkenyl.

[1385] In one embodiment, Rxis C2-C6 alkynyl.

[1386] In one embodiment, Rxis C3-C8cycloalkyl.

[1387] In one embodiment, Rxis heterocyclyl.

[1388] In one embodiment, Rxis aryl.

[1389] In one embodiment, Rxis heteroaryl.

[1390] In one embodiment, in the compound of Formula (I), R3is H.

[1391] In one embodiment, R3is Ci-Ce alkyl.

[1392] In one embodiment, R3is methyl.

[1393] In one embodiment, R3is ethyl.

[1394] In one embodiment, R3is n-propyl

[1395] In one embodiment, R3is iso-propyl

[1396] In one embodiment, R3is iso-butyl.

[1397] In one embodiment, R3is sec-butyl

[1398] In one embodiment, R3is tert-butyl

[1399] In one embodiment, R3is Cs alkyl.

[1400] In one embodiment, R3is Ce alkyl.

[1401] In one embodiment, R3is C2-C6 alkenyl,

[1402] In one embodiment, R3is C2-C6 alkynyl.

[1403] In one embodiment, R3is C3-C8cycloalkyl.

[1404] In one embodiment, R3is heterocyclyl.

[1405] In one embodiment, R3is aryl.

[1406] In one embodiment, R3is heteroaryl.

[1407] In one embodiment, R3is O(Ry).

[1408] In one embodiment, R3is N(Ry)2.

[1409] In one embodiment, R3is SRy.

[1410] In one embodiment, R3is S(=O)nRy.

[1411] In one embodiment, Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

[1412] In one embodiment, Ryis Ci-Ce alkyl.

[1413] In one embodiment, Ryis methyl.

[1414] In one embodiment, Ryis ethyl.

[1415] In one embodiment, Ryis n-propyl

[1416] In one embodiment, Ryis iso-propyl

[1417] In one embodiment, Ryis iso-butyl.

[1418] In one embodiment, Ryis sec-butyl

[1419] In one embodiment, Ryis tert-butyl

[1420] In one embodiment, Ryis C5 alkyl.

[1421] In one embodiment, Ryis Ce alkyl.

[1422] In one embodiment, Ryis allyl.

[1423] In one embodiment, Ryis propargyl.

[1424] In one embodiment, Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein each is substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[1425] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein each R is hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

[1426] In one embodiment, R3is O(Ry); Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R, wherein one R is hydrogen, and the other R is

[1427] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H; andR3is -O(Ci-C4alkyl).

[1428] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is H; andR3is - O(C2-Ce alkynyl).

[1429] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H; andR3is -O(Ci-C4alkyl).

[1430] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is H; andR3is - O(C2-Ce alkynyl).

[1431] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is H; andR3is -O(Ci-C4alkyl).

[1432] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is H; andR3is - O(C2-Ce alkynyl).

[1433] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=0)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(Ci-C4alkyl).

[1434] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(C2-Ce alkynyl).

[1435] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(Ci-C4alkyl).

[1436] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(C2-Ce alkynyl).

[1437] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(Ci-C4alkyl).

[1438] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is - O(C2-Ce alkynyl).

[1439] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is -O(Ci-C4alkyl).

[1440] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is - O(C2-Ce alkynyl).

[1441] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is -O(Ci-C4alkyl).

[1442] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is - O(C2-Ce alkynyl).

[1443] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is -O(Ci-C4alkyl).

[1444] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is C1-C4 alkyl;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is - O(C2-Ce alkynyl).

[1445] In one aspect, this application pertains to a compound of Formula (I), wherein: X is CH2;each R1is H;each R2is H; andR3is -O(Ci-C4alkyl).

[1446] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is H;each R2is H; andR3is -O(C2-Ce alkynyl).

[1447] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is H; andR3is -O(Ci-C4alkyl).

[1448] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is H; andR3is -O(C2-Ce alkynyl).

[1449] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is H; andR3is -O(Ci-C4alkyl).

[1450] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is H; andR3is -O(C2-Ce alkynyl).

[1451] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; andR3is -O(Ci-C4alkyl).

[1452] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis C1-C6alkyl, m is 0, and Z is absent; and R3is —O(C2-C6alkynyl).

[1453] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(Ci-C4alkyl).

[1454] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(C2-Ce alkynyl).

[1455] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(Ci-C4alkyl).

[1456] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 0, and Z is absent; and R3is -O(C2-Ce alkynyl).

[1457] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; and R3is -O(Ci-C4alkyl).

[1458] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CH2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis C1-C6alkyl, m is 1, and Z is O; and R3is -O(C2-C6alkynyl).

[1459] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis C1-C6alkyl, m is 1, and Z is O; and R3is -O(C1-C4alkyl).

[1460] In one aspect, this application pertains to a compound of Formula (I), wherein:X is CF2;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis C1-C6alkyl, m is 1, and Z is O; and R3is -O(C2-C6alkynyl).

[1461] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis Ci-Ce alkyl, m is 1, and Z is O; andR3is -O(Ci-C4alkyl).

[1462] In one aspect, this application pertains to a compound of Formula (I), wherein:X is O;each R1is H;each R2is -(CH2)m-Z-C(=O)-Rx, Rxis C1-C6alkyl, m is 1, and Z is O; and R3is -O(C2-C6alkynyl).

[1463] In one aspect, this application pertains to a compound of Formula (I) that is a compound of Formula (la),OR10—O\ n0-P,R10^ / ° OH-1-0bu H0HO^R3(Ia), wherein R1and R3are as defined herein.

[1464] In one aspect, this application pertains to a compound of Formula (I) that is a compound of Formula (lb),Owherein R1and R3are as defined herein.

[1465] In one aspect, this application pertains to a compound of Formula (I) that is a compound of Formula (Ic),wherein R1and R3are as defined herein.

[1466] In one aspect, this application pertains to a compound of Formula (I) that is a compound of Formula (Id),wherein R1and R3are as defined herein.

[1467] In one aspect, this application pertains to a compound of Formula (I), wherein the compound is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.SYNTHESIS OF COMPOUNDS OF FORMULA (I)

[1468] The compounds of the application may be synthesized according to the methods established in the art. See, for example, Topics in Current Chemistry. Phosphorus Chemistry I. Asymmetric Synthesis and Bioactive Compounds. Jean-Luc Montchamp, Ed., Springer International Published, Switzerland, 2015, which is incorporated by reference in its entirety.)

[1469] In one embodiment, a compound of formula (I) may be prepared according to the Scheme below.H2 / Pd / C, EtOH, H2O

[1470] Intermediate 1 (Acta. Chem. Scand. 1972, 26, 4143-4146, and Aust. J. Org. Chem. 1999, 447-550, R3= methoxy, both of which are incorporated by reference in their entirety) is reacted with the carbanion generated by the reaction of Wittig-Horner reagent 2 with a base (e.g., sodium hydride) to provide bisphosphonate ester 3. Hydrogenation of 3 leads to reduction of the carbon-carbon double bond and removal of the benzyl groups to provide 4. Compound 4 can be further functionalized by reacting with an appropriate electrophile (acetyl bromide, acetoxymethyl bromide) and, optionally, a base (e.g., 4-dimethylaminopyridine) to provide compound 5.PHARMACEUTICAL COMPOSITIONS

[1471] The pharmaceutical compositions or formulations of the application, in addition to comprising a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, may further comprising one or more of the following excipients: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent (e.g., starches or partially gelatinized starches, sorbitol, mannitol, malitol, microcrystalline cellulose); disintegrant (e.g., sodium croscarmellose and sodium starch glycolate); plasticizers (e.g., glycerol, vitamin E TPGS, triacetin); anti-tacking agent (e.g., tricalcium phosphate, silicon dioxide, bentonite); wetting agent (sodium lauryl sulfate, sodium stearyl fumarate, polyoxyethylene 20 sorbitan mono- oleate (e.g., Tween™); sweetener (sucralose, sorbitol, and xylitol); colorant (FD& C Blue # 1 Aluminum Lake, FD& C Blue #2, other FD& C Blue colors, titanium dioxide, iron oxide); flavorant (menthol, peppermint oil, almond oil); glidant (colloidal silica, precipitated silica, and talc); pH adjuster (arginine, tartaric acid, sodium hydrogen carbonate, adipic acid); or surfactant (ammonium lauryl sulfate, sodium lauryl sulfate (sodium dodecyl sulfate, SLS, or SDS), sodium laureth sulfate, sodium myreth sulfate, dioctyl sodium sulfosuccinate, fatty acid esters of glycerol, poloxamers).

[1472] Antioxidants, include, without limitation, hindered phenols (e.g., tetrakis [methylene (3,5-di-t-butyl-4-hydroxyhydrocinnamate)]methane), less-hindered phenols, and semihindered phenols; phosphates, phosphites, and phosphonites (e.g., tris (2,4-di-t-butylphenyl) phosphate); thio compounds (e.g., distearyl thiodipropionate, dilaurylthiodipropionate); various siloxanes; and various amines (e.g., polymerized 2,2,4-trimethyl-l,2-dihydroquinoline). In one embodiment, the antioxidant is selected from the group consisting of distearyl thiodipropionate, dilauryl thiodipropionate, octadecyl-3, 5-di-t-butyl-4-hydroxyhydrocinnamate, benzenepropanoic acid, 3,5-bis (l,l-dimethylethyl)-4-hydroxy-thiodi-2,l-ehtanediyl ester, stearyl 3-(3,5 -di-t-butyl-4-hydroxyphenyl) propionate, octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate, 2,4-bis(dodecylthiomethyl)-6-methylphenol, 4,4'-thiobis(6-tert-butyl-m-cresol), 4,6-bis (octylthiomethyl)-o-cresol, 1,3,5-tris(4-tert-butyl-3-hydroxy-2,6-dimethyl benzyl)-l,3,5-triazine-2,4,6-(lH,3H,5H)-trione, pentaerythritol tetrakis (3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate), 2',3-bis[[3-[3,5-di-tert-butyl-4-hydroxyphenyl]propionyl]]propionohydrazide, and mixtures thereof. In one embodiment, the antioxidant is butylated hydroxyanisole, butylated hydroxytoluene (BHT), sodium metabisulfite, propyl gallate, cysteine, methionine, or ethylenediaminetetraacetic acid (EDTA).

[1473] Buffering agents are includes in the pharmaceutical formulations of the application in order to prevent or reduce a pH change in the dosage form after administration to a subject. Representative buffering agents include, without limitation, borates, borate-polyol complexes, succinate, phosphate buffering agents, citrate buffering agents, acetate buffering agents, carbonate buffering agents, organic buffering agents, amino acid buffering agents, or combinations thereof. In one embodiment, the buffering agent is citric acid, sodium phosphate, sodium citrate, sodium acetate, sodium hydroxide, acetic acid, potassium chloride, sodium chloride, sodium bicarbonate, L-arginine, a cholic acid derivative, or tris(hydroxymethyl)aminomethane (TRIS).

[1474] Bulking agents, or fillers, include, without limitation, lactose monohydrate, microcrystalline cellulose, cellulose acetate, calcium carbonate, potato starch, sucrose, and sorbitol, and dextrose.

[1475] Non-aggregating agents, or lubricants, include, without limitation, boric acid, PEG4000, PEG6000, sodium oleate, sodium benzoate, sodium acetate, sodium acetate, sodium stearate, sodium stearyl fumarate, sodium lauryl sulfate, magnesium lauryl sulfate, magnesium stearate, stearate, stearic acid, talc, hydrogenated oil, and glyceryl behenate.

[1476] Binding agents include, without limitation, acacia, gelatin, starch paste, polyvinylpyrrolidone, polyethylene glycol, glucose, carboxymethyl cellulose, and povidone.

[1477] The pharmaceutical compositions or formulations of the application can be administered via a route selected from the group consisting of route selected from the group consisting of oral administration, nasal (intranasal) administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.

[1478] In one embodiment, the formulations of the application are intended for oral administration. Example of oral dosage forms contemplated herein include, without limitation,tablets, capsules, gels, caplets, gelcaps, geltabs, liquids, syrups, pellets, sachets, dragees, pills, lozenges, granules, powders, or powder-in-capsule.METHODS OF TREATMENT

[1479] In one aspect, the methods of the application pertain to treating and / or preventing a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1480] In one aspect, the methods of the application pertain to treating a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1481] In one embodiment, the method of the applications pertains to treating a neurodegenerative disease, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1482] In one embodiment, the method of the applications pertains to preventing a neurodegenerative disease, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1483] In one embodiment, the methods of the application pertain to treating age-related memory impairment.

[1484] In one embodiment, the methods of the application pertain to treating age-related cognitive impairment.

[1485] In one embodiment, the neurodegenerative disease is Huntington's Disease (HD).

[1486] Huntington's Disease (HD), also known as Huntington's Chorea, is a progressive disorder of motor, cognitive and psychiatric disturbances. The mean age of onset for this disease is age 35-44 years, although in about 10% of cases, onset occurs prior to age 21, and the average lifespan post-diagnosis of the disease is 15-18 years. HD is prevalent in about 3 to 7 among 100,000 people of western European descent.

[1487] In one aspect, the application pertains to a method of treating Huntington’s disease comprising the administration to a subject in need thereof of an effective amount of acompound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1488] In one aspect, the application pertains to a method of preventing Huntington’s disease comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1489] In one embodiment, the neurodegenerative disease is Parkinson’s Disease (PD).

[1490] In one aspect, the application pertains to a method of preventing PD comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1491] In one embodiment, the neurodegenerative disease is Amyotrophic lateral sclerosis (ALS).

[1492] Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, causes the death of neurons controlling voluntary muscles. The term motor neuron disease can also be used for a group of conditions of which ALS is the most common. ALS is characterized by stiffness, twitching, and weakness of muscles and their decrease in size. This disease may begin with weakness in the arms or legs, or with difficulty speaking or swallowing. About half of the people affected develop at least mild difficulties with behavior and thinking, and most experience pain as well. Most who suffer from the disease eventually lose the ability to walk, use their hands / extremities, speak, swallow, and breathe. There are three types of ALS categorized by where the symptoms first start: (1) limb onset, (2) trunk onset that affects the breathing muscles, and (3) bulbular onset that affects speech and swallowing first. In all of the types, the condition eventually spreads to the other muscles and paralyzes them. The underlying mechanism involves damage to both upper and lower motor neurons. The diagnosis is based on a patient's symptoms, with testing done to rule out other potential causes.

[1493] In one aspect, the application pertains to a method of treating amyotrophic lateral sclerosis comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (I’), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1494] In one aspect, the application pertains to a method of preventing amyotrophic lateral sclerosis comprising the administration to a subject in need thereof of an effective amount of acompound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1495] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the rate of progressive death of motor neurons is slowed or stopped.

[1496] In one embodiment, the neurodegenerative disease is Alzheimer’s disease (AD).

[1497] Alzheimer’s disease (AD) is the most common form of dementia in the elderly. There is currently no efficacious treatment for the disease. AD is characterized by senile plaques (P-amyloid) accumulation in the brain. Agents that reverse synapse impairments and P-amyloid accumulation represent promising therapeutic candidates for the treatment and / or prevention of AD.

[1498] In one aspect, the application pertains to a method of treating Alzheimer’s disease comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (I’), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1499] In one aspect, the application pertains to a method of preventing Alzheimer’s disease comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (I’), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1500] In one embodiment, the method of the application pertains to treating a neurodevelopmental disorder, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (I’), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1501] In one embodiment, the method of the application pertains to preventing a neurodevelopmental disorder, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (I’), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1502] In one embodiment, the neurodevelopmental disorder is an autism spectrum disorder (ASD).

[1503] Autism spectrum disorders (ASD) are characterized by complex developmental disability that interferes with the normal development of the brain, particularly impacting social interaction and communication skills. It typically appears during the first three years of life. Autistic individuals have difficulties in verbal and non-verbal communication, social interactions, and leisure or play activities. Impairment in social interaction range fromdifficulty initiating and maintaining interaction, impaired ability to recognize and experience emotions, and difficulty processing and appreciating the feelings of others. Communication deficits vary amongst autistic individuals, with some autistic individuals having severely limited form of communication to individuals having significant language skills. Repetitive and stereotypic behaviors include complex rituals, difficulty in adapting to change, and unusual movements such as hand flapping. Some characteristic behavior which may be useful for diagnosing autism includes lack of or delay in spoken language, repetitive use of language or motor mannerisms (hand flapping or twirling objects), little or no eye contact, persistent fixation on certain objects, and lack of interest in socializing.

[1504] In one aspect, the application pertains to a method of treating an autism spectrum disorder comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1505] In one aspect, the application pertains to a method of preventing an autism spectrum disorder comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1506] In one embodiment, the autism spectrum disorder is an autistic disorder.

[1507] In one embodiment, the autism spectrum disorder is Asperger's syndrome.

[1508] In one embodiment, the autism spectrum disorder is Fragile X syndrome.

[1509] In one embodiment, the autism spectrum disorder is a childhood disintegrative disorder.

[1510] In one embodiment, the neurodevelopmental disorder is Angelman Syndrome (AS).

[1511] Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by developmental delay, intellectual disability, speech impairment, motor problems, sleep alteration and neurological symptoms caused by genetic alterations of regions of the chromosome 15. These genetic defects affect several imprinted genes of which ubiquitin ligase 3A (UBE3A) seems to be the most common. Symptoms of AS can include: developmental delays such as a lack of crawling or babbling at 6 to 12 months, attenuated mental development, no or minimal speech, ataxia (inability to move, walk, or balance properly), stiff or jerky movements (e.g., hand-flapping), hyperactivity, trembling in the arms and legs, frequent smiling and laughter, bouts of inappropriate laughter, widely spaced teeth, a happy, excitable personality, epilepsy, an electroencephalographic abnormality with slowing and notched wave and spikes, seizures which usually begin at 2 to 3 years of age and may be accompanied by myoclonus and atypical absence, partial seizures with eye deviation and vomiting, a small headwhich is noticeably flat in the back (microbrachyoephaly), crossed eyes (strabismus), thrusting of the tongue and suck / swallowing disorders, protruding tongue, excessive chewing / mouthing behaviors, hyperactive lower extremity deep tendon reflexes, wide-based gait with pronated or valgus-positioned ankles, increased sensitivity to heat, walking with the arms up in the air, fascination with water or crinkly items such as some papers or plastics, obesity in older children, constipation, a jutting lower jaw, light pigmentation of the hair, skin, and eyes (hypopigmentation), frequent drooling, prognathia, feeding problems and / or truncal hypotonia during infancy, and / or scoliosis. Symptoms are usually not evident at birth and are often first evident as developmental delays such as a failure to crawl or babble between the ages of 6 to 12 months as well as slowing head growth before the age of 12 months. Individuals with Angelman Syndrome may also suffer from sleep disturbances including difficulty initiating and maintaining sleep, prolonged sleep latency, prolonged wakefulness after sleep onset, high number of night awakenings and reduced total sleep time, enuresis, bruxism, sleep terrors, somnambulism, nocturnal hyperkinesia, and snoring.

[1512] Severity of symptoms for AS can be measured clinically (Williams et al., American Journal of Medical Genetics 2005 140 A; 413-8, incorporated herein by reference) and quantification of the severity of different symptoms can also be carried out (Lossie et al., Journal of Medical Genetics 2001, 38; 834-845, incorporated herein by reference; Ohtsuka et al., Brain and Development 2005, 27; 95-100, incorporated herein by reference). This may include the extent of language ability, degree of independent mobility, frequency and severity of seizures, ability to comprehend language, acquisition of motor skills, growth parameters. A screening procedure for suspected Angelman syndrome patients that quantifies the severity of 22 distinct criteria (Lossie et al., Journal of Medical Genetics 2001, 38) can be used. Other measurements of AS severity include psychometric methods to distinguish the degree of developmental delay with respect to psychomotor developmental achievement, visual skills, social interactions based on non-verbal events, expressive language abilities, receptive language abilities, and speech impairment. The degree of gait and movement disturbances as well as attention ability and the extent of EEG abnormalities can be measured (Williams et al., American Journal of Medical Genetics 2005 140A; 413-8). At appropriate age intellectual ability tests can also be used, such as the Kaufman Brief Intelligence Test-2 (KBIT-2; Kaufman & Kaufman, Circle Pines, MN: American Guidance Services; 2004, incorporated herein by reference). One or more of the above characteristics can be used to evaluate the effectiveness of treatment with the present compositions.

[1513] In an embodiment, assessment protocols to evaluate the effect of treatment include neurological and neurovisual examination and the evaluation of motor (e.g. Gross Motor Function Measure Scale), cognitive (e.g. Griffiths Mental Development Scale and Uzgiris-Hunt Scale and spatial working memory tests); adaptive (e.g. Vineland Adaptive Behavioral Scale); communication (e.g. MacArthur-Bates Communicative Development Inventory and video-recordings children’s verbal expression), behavioral aspects (e.g. IPDDAG Scale) and neurovisual aspects as described in Micheletti et al., (Ital J Pediatr. 2016; 42(1): 91), incorporated herein by reference.

[1514] In one aspect, the application pertains to a method of treating Angelman Syndrome comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1515] In one aspect, the application pertains to a method of preventing Angelman Syndrome comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1516] In one aspect, the application pertains to a method of treating Angelman Syndrome comprising the administration to a subject in need thereof of an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[1517] In one embodiment, the neurological condition is pervasive developmental disordersnot otherwise specified.

[1518] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the autism spectrum disorder may be treated by decreasing one or more symptoms of the disorder, including, for example, irritability, lethargy, hyperactivity, inadequate eye contact, or inappropriate speech.

[1519] In one embodiment, the method of the application pertains to treating age-related memory impairment, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1520] In one embodiment, the method of the application pertains to preventing age-related memory impairment, wherein the method comprises administering an effective amount of acompound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1521] In one embodiment, the method of the application pertains to treating age-related cognitive impairment, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1522] In one embodiment, the method of the application pertains to preventing age-related cognitive impairment, wherein the method comprises administering an effective amount of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, to a subject in need thereof.

[1523] Age-related memory impairment, or memory impairment, memory loss, or forgetting, refers to an inability to retain information either in the short-term or long-term. It may include difficulties with cognitive, executive, and language performance, executive function and visual memory. It may also include difficulties with short-term memory, which is the temporary storage of information while processing the same or other information, and / or inability or difficulty with verbal working memory, i.e., phonological memory.

[1524] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the subject develops an improved ability to retain information in the short-term.

[1525] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the subject develops an improved ability to retain information in the long-term.

[1526] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the subject’s visual memory improves.

[1527] In one embodiment, upon administration of a compound of Formula (I), Formula (F), or Formula (I”), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, the subject’s phonological memory improves.NUMBERED EMBODIMENTS

[1528] The below numbered embodiments apply to Formula (I’):Al. A compound of Formula (F)R3(D, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:Xis CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;R1is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl;alternatively, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R6, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH, or SH;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.A2. The compound of embodiment Al, wherein X is O.A3. The compound of embodiment Al, wherein X is C(Y1)(Y2).A4. The compound of embodiment A3, wherein Y1and Y2are each H.A5. The compound of any one of embodiments A1-A4, wherein R1is Ci-Ce alkyl.A6. The compound of any one of embodiments A1-A5, wherein R1is methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, or tert-butyl.A7. The compound of any one of embodiments A1-A6, wherein R1is methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.A8. The compound of any one of embodiments A1-A7 wherein each R2is H.A9. The compound of any one of embodiments A1-A7, wherein at least one R2is -(CH2)m- C(=O)-RX.A10. The compound of any one of embodiments A1-A9, wherein m is 0.Al 1. The compound of any one of embodiments A1-A9, wherein m is 1.A12. The compound of any one of embodiments Al-All, wherein at least one Rxis Ci-Ce alkyl.A13. The compound of any one of embodiments A1-A12, wherein at least one Rxis methyl.A14. The compound of any one of embodiments A1-A13, wherein R3is H.A15. The compound of any one of embodiments A1-A13, wherein R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.A16. The compound of any one of embodiments A1-A13, wherein R3is N(Ry)2, SRy, or S(=O)nRyA17. The compound of any one of embodiments A1-A13 wherein, R3is O(Ry).A18. The compound of any one of embodiments A1-A17, wherein at least one Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.Al 9. The compound of any one of embodiments Al -Al 8, wherein at least one Ryis Ci-Ce alkyl.A20. The compound of any one of embodiments Al -Al 9, wherein at least one Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R.A21. The compound of any one of embodiments A1-A20, wherein R5is H.22. The compound of any one of embodiments A1-A20, wherein R5is Ci-Ce alkyl.23. The compound of any one of embodiments A1-A20, wherein R5is H, methyl, isopropyl, iso-butyl, sec-butyl, -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl, substituted by para-OH, -Cffc-imidazolyl, or -CTfc-indolyl.A24. The compound of any one of embodiments 1-A23, wherein R6is H, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.A25. The compound of any one of embodiments A1-A23, wherein R6is C3-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl.A26. The compound of any one of embodiments A1-A23, wherein R6is aryl or heteroaryl.A27. The compound of any one of embodiments A1-A26, wherein R7is H.A28. The compound of any one of embodiments A1-A27, wherein each Ris, independently, hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.A29. The compound of embodiment 1, wherein the compound of Formula (T) is Formula (I’a):(I’a),or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.A30. The compound of embodiment Al, wherein the compound of Formula (F) is selected from a compound of Formula (I’c), Formula (I’d), Formula (I’e), and Formula (I’f):R6R6(I’d),(I’f), or a pharmaceutically acceptable salt or solvate thereof.A31. The compound of embodiment Al, wherein the compound is:or a pharmaceutically acceptable salt or solvate thereof.A32. A pharmaceutical composition comprising a compound of any one of embodiments Al-A31 and one or more pharmaceutically acceptable excipients.A33. The pharmaceutical composition of embodiment A32, wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.A34. A method of treating a neurodegenerative disease, neurodevel opmental disorder, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound according to embodiments A1-A31 or a pharmaceutical composition according to embodiments A32 or A33.A35. The method of embodiment A34, wherein the neurodegenerative disease is amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease.A36. The method of embodiment A34, wherein the neurodevelopmental disorder is an autism spectrum disorder.A37. The method of embodiment A36, wherein the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, Angelman syndrome, or pervasive developmental disorder-not otherwise specified.A38. The method of any one of embodiments A34-A37, wherein the compound of Formula (I’) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.A39. A compound of embodiments A1-A31, or a pharmaceutical composition of embodiment 32 or 33, for use in the treatment of a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment.A40. Use of a compound according to embodiments A1-A31, or a pharmaceutical composition according to embodiment A32 or A33, for the preparation of a medicament for the treatment of a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment.

[1529] The below numbered embodiments apply to Formula (I”):Bl. A compound of Formula (I”):(I”), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is C(Y1)(Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;each R5is, independently, H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;each R7is, independently, H or C1-C3 alkyl;alternatively, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR;each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH, or SH;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.B2. The compound of embodiment Bl, wherein X is O.B3. The compound of embodiment Bl, wherein X is C(Y1)(Y2).B4. The compound of embodiment B3, wherein Y1and Y2are each H.B5. The compound of any one of embodiments B1-B4, wherein each R1is Ci-Ce alkyl.B6. The compound of any one of embodiments B 1-B5, wherein each R1is methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, or tert-butyl.B7. The compound of any one of embodiments B 1-B6, wherein each R1is methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.B8. The compound of any one of embodiments B1-B7 wherein each R2is H.B9. The compound of any one of embodiments Bl -B7, wherein at least one R2is -(CH2)m-C(=O)-RX.BIO. The compound of any one of embodiments B1-B9, wherein m is 0.Bl 1. The compound of any one of embodiments B1-B9, wherein m is 1.B12. The compound of any one of embodiments Bl-Bll, wherein at least one Rxis Ci-Ce alkyl.B13. The compound of any one of embodiments Bl -Bl 2, wherein at least one Rxis methyl.B14. The compound of any one of embodiments Bl -Bl 3, wherein R3is H.B15. The compound of any one of embodiments B1-B13, wherein R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.B16. The compound of any one of embodiments B1-B13, wherein R3is N(Ry)2, SRy, or S(=O)nRyB17. The compound of any one of embodiments Bl -Bl 3, wherein R3is O(Ry).B18. The compound of any one of embodiments B1-B17, wherein at least one Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.Bl 9. The compound of any one of embodiments Bl -Bl 8, wherein at least one Ryis Ci-Ce alkyl.B20. The compound of any one of embodiments Bl -Bl 9, wherein at least one Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R.B21. The compound of any one of embodiments B 1-B20, wherein each R5is H.B22. The compound of any one of embodiments Bl -B20, wherein each R5is Ci-Ce alkyl.B23. The compound of any one of embodiments Bl -B20, wherein each R5is H, methyl, isopropyl, iso-butyl, sec-butyl, -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl substituted by para-OH, -CFk-imidazolyl, or -CFb-indolyl.B24. The compound of any one of embodiments B1-B23, wherein each R7is H.B25. The compound of any one of embodiments Bl -B24, wherein each R is, independently, hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.B26. The compound of embodiment Bl, wherein the compound of Formula (I”) is Formula (I”a):or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.B27. The compound of embodiment Bl, wherein the compound of Formula (I”) is Formula (I”b):or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.B28. The compound of embodiment Bl, wherein the compound isor a pharmaceutically acceptable salt or solvate thereof.B29. A pharmaceutical composition comprising a compound of any one of embodiments Bl-B28 and one or more pharmaceutically acceptable excipients.B30. The pharmaceutical composition of embodiment B29, wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.B31. A method of treating a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound according to embodiments B1-B28 or a pharmaceutical composition according to embodiments B29 or B30.B32. The method of embodiment B31, wherein the neurodegenerative disease is amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease.B33. The method of embodiment B31, wherein the neurodevelopmental disorder is an autism spectrum disorder.B34. The method of embodiment B33, wherein the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, Angelman syndrome, or pervasive developmental disorder-not otherwise specified.B35. The method of any one of embodiments B31-B34, wherein the compound of Formula (I”) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.B36. A compound of embodiments Bl -B28, or a pharmaceutical composition of embodiment B29 or B30, for use in the treatment of a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment.B37. Use of a compound according to embodiments B1-B28, or a pharmaceutical composition according to embodiment B29 or B30, for the preparation of a medicament for the treatment of a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment.

[1530] The below numbered embodiments apply to Formula (I):Cl. A compound of Formula (I)(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is C(Y1)(Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=0)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2,provided that:when X is C(Y1)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis not methyl or propargyl; andwhen X is C(Y1)(Y2); Y1and Y2are each H; each R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis not 2,4-dimethylphenyl.C2. The compound of embodiment Cl, wherein X is O.C3. The compound of embodiment Cl, wherein X is C(Y1)(Y2).C4. The compound of embodiment C3, wherein Y1and Y2are each H.C5. The compound of any one of embodiments C1-C4, wherein each R1is, independently, Ci-C6alkyl.C6. The compound of any one of embodiments C1-C5, wherein each R1is, independently, methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, or tert-butyl.C7. The compound of any one of embodiments C1-C6, wherein each R1is, independently, methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.C8. The compound of any one of embodiments C1-C7 wherein each R2is H.C9. The compound of any one of embodiments C1-C7, wherein each R2is -(CH2)m-Z-C(=O)-RX.CIO. The compound of any one of embodiments C1-C9, wherein m is 0 and Z is absent.Cl 1. The compound of any one of embodiments C1-C9, wherein m is 1 and Z is O.C12. The compound of any one of embodiments Cl-Cl 1, wherein Rxis Ci-Ce alkyl.C13. The compound of any one of embodiments C1-C12, wherein Rxis methyl.C14. The compound of any one of embodiments C1-C13, wherein R3is H.C15. The compound of any one of embodiments C1-C13, wherein R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.C16. The compound of any one of embodiments C1-C13, wherein R3is N(Ry)2, SRy, or S(=O)nRy.C17. The compound of any one of embodiments C1-C13, wherein R3is O(Ry).C18. The compound of any one embodiments C1-C17, wherein Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.C19. The compound of any one embodiments C1-C18, wherein Ryis Ci-Ce alkyl.C20. The compound of any one embodiments Cl -Cl 9, wherein Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R.C21. The compound of any one of embodiments C1-C20, wherein each Ris hydrogen, Ci- Ce alkyl, aryl, or heteroaryl.C22. The compound of embodiment Cl, wherein the compound is a compound of Formula (la),R1O^fR3(Ia), wherein R1and R3are as defined in embodiment Cl.C23. The compound of embodiment Cl, wherein the compound is a compound of Formula (Ib),wherein R1and R3are as defined in embodiment Cl.C24. The compound of embodiment Cl, wherein the compound is a compound of Formulawherein R1and R3are as defined in embodiment Cl.C25. The compound of embodiment Cl, wherein the compound is a compound of Formula (Id),wherein R1and R3are as defined in embodiment Cl.C26. A pharmaceutical composition comprising a compound of any one of embodiments Cl-C25 and one or more pharmaceutically acceptable excipients.C27. The pharmaceutical composition of embodiment C26, wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.C28. A method of treating a neurodegenerative disease, neurodevelopmental disorder, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound of formula (I),(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Xis CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=0)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.C29. The method of embodiment C28, wherein the neurodegenerative disease is Angelman syndrome, amyotrophic lateral sclerosis, Huntington’s disease, or Alzheimer’s disease.C30. The method of embodiment C28, wherein the neurodevelopmental disorder is an autism spectrum disorder.C31. The method of embodiment C30, wherein the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder, or pervasive developmental disorder-not otherwise specified.C32. The method of any one of embodiments C28-C31, wherein the compound of formula (I) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.EXAMPLES

[1531] The disclosure is further illustrated by the following examples, which are not to be construed as limiting this disclosure in scope or spirit to the specific procedures herein described. It is to be understood that the examples are provided to illustrate certain embodiments and that no limitation to the scope of the disclosure is intended thereby. It is to be further understood that resort may be had to various other embodiments, modifications, and equivalents thereof which may suggest themselves to those skilled in the art without departing from the spirit of the present disclosure and / or scope of the appended claims.General Synthetic Methods

[1532] All solvents used were commercially available and were used without further purification. Reactions were typically run using anhydrous solvents under an inert atmosphere of nitrogen.

[1533] Liquid Chromatography-Mass Spectrometry Method A:

[1534] Total ion current (TIC) and DAD UV chromatographic traces together with MS and UV spectra associated with the peaks were taken on a UPLC / MS Acquity™ system equipped with PDA detector and coupled to a Waters single quadrupole mass spectrometer operating in alternated positive and negative electrospray ionization mode. [LC / MS-ES (+ / -): analyses performed using an Acquity UPLCTMCSH, Cl 8 column (50 X 2.1mm, 1.7 u m particle size), column temperature 40° C, mobile phase: A-water + 0.1% HCOOH / B- CH3CN + 0.1% HCOOH, flow rate: 1.0 mL / min, runtime = 2.0 min, gradient: t=0 min 3%B, t= 1.5 min 99.9% B, t = 1.9 min 99.9% B, t= 2.0 min 3%B, stop time 2.0 min. Positive ES 100-1000, Negative ES 100-1000, UV detection DAD 210-350 nm.

[1535] Liquid Chromatography-Mass Spectrometry Method B

[1536] Total ion current (TIC) and DAD UV chromatographic traces together with MS and UV spectra associated with the peaks were taken on a UPLC / MS Acquity TM system equipped with PDA detector and coupled to a Waters single quadrupole mass spectrometer operating in alternated positive and negative electrospray ionization mode. [LC / MS-ES (+ / -): analyses performedusingan Acquity UPLCTMCSH, Cl 8 column (50 X 2.1mm, 1.7 u m particle size), column temperature 50° C, mobile phase: A- HCOONH4 0.025M pH 3 B- ACN + 0.1% HCOOH, flow rate: 0.35 mL / min, runtime = 10.0 min, gradient: t=0 min 20%B, t= 5.5 min 80% B, t = 7.5 min 80% B, t= 8.0 min 20% B, stop time 10.0 min. Positive ES 100-1000, Negative ES 100-1000, UV detection DAD 210-350 nm.

[1537] Methods of Characterization

[1538] 1H Nuclear magnetic resonance (NMR) spectroscopy was carried out using one of the following instruments: a Bruker Avance 400 instrument equipped with probe DUAL 400MHz SI, a Bruker Avance 400 instrument equipped with probe 6 SI 400 MHz 5mm 1H-13C ID, a Bruker Avance III 400 instrument with nanobay equipped with probe Broadband BBFO 5 mm direct, a 400 MHz Agilent Direct Drive instrument with ID AUTO-X PFG probe, all operating at 400 MHz, or an Agilent VNMRS500 Direct Drive instrument equipped with a 5 mm Triple Resonance 1H{13C / 15N] cryoprobe operating at 500 MHz. The spectra were acquired in the stated solvent at around room temperature unless otherwise stated. In all cases, NMR data were consistent with the proposed structures. Characteristic chemical shifts are given in parts-per-million using conventional abbreviations for designation of major peaks: e.g. s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; br, broad.

[1539] Preparation of intermediates [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6- methoxy-tetrahydropyran-2-yl] methanol and [(E)-2-[(2R,3R,4S,5S,6S)-6-methoxy- 3,4,5-tris(phenylmethoxy)oxan-2-yl]ethenyl]phosphonic acid

[1540] A7ep 1 -Synthesis of (2S,3S,4S,5S, 6R) -2 -methoxy-6- [ (triphenylmethoxy)methyl oxane -3,4,5 -triolPh

[1541] (2R,3S,4S,5S,6S)-2-(hydroxymethyl)-6-methoxyoxane-3,4,5-triol (25.0 g, 128.75 mmol), [chloro(diphenyl)methyl]benzene (35.89 g, 128.75 mmol) and Pyridine (25 mL) were mixed at room temperature, the mixture was heated at 100°C for 30 min. UPLC-Ms reaction completed (check by NMR)

[1542] Dichloromethane (400 ml) was added and the mixture was stirred for 1 h at room temperature, the slurry was washed with NH4C1 aq sat (100 ml x 2) and the organic layer was collected and concentrated to afford an oil, Cyclohexane (150 ml) was added and the mixture was heated under stirring for 1 hour at 65°C, the mixture was let to cool to 20° C and left at 20°C for 10 h without stirring. The cyclohexane solution was discarded, the oil was collected and concentrated to afford (2S,3S,4S,5S,6R)-2-methoxy-6- [(triphenylmethoxy )methyl]oxane-3,4,5-triol as white foam (51 g, 0.117 mol).

[1543] 'H NMR (400 MHz, Chloroforms / ) 6 7.47 - 7.42 (m, 7H), 7.35 - 7.28 (m, 8H), 4.72 (d, J= 1.6 Hz, 1H), 3.95 - 3.90 (m, 1H), 3.83 - 3.62 (m, 3H), 3.44 (qd, J= 9.8, 5.1 Hz, 2H), 3.38 (s, 3H), 2.70 (d, J= 2.3 Hz, 1H), 2.48 (d, J= 4.9 Hz, 1H), 2.24 (d, J= 4.3 Hz, 1H).

[1544] Step 2 - Synthesis of (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6- ( trityloxymethyl)tetrahydropyran

[1545] Reaction performed under Nitrogen: (2S,3S,4S,5S,6R)-2-methoxy-6-(trityloxymethyl) oxane- 3,4,5-triol (51 g, 117 mmol) was dissolved in anhydrous DMF (450 mL) and the mixture was cooled to 0° C. Sodium hydride 60% dispersion in mineral oil (23.37 g, 584.2 mmol) was added portion wise in 1 hour, then the mixture was stirred at 0°C for 30 minutes. Chloromethylbenzene (59.16 g, 467.35 mmol) was slowly added to the reaction mixture, the reaction was stirred 10 minutes at 0° C and allowed to warm up to 20° C. The mixture was stirred at 20° C overnight.

[1546] From UPLC analysis no SM was any longer visible. The mixture was cooled to 5° C, then ice was added portion wise to quench the reaction (very slow addition with considerable effervescence formation, to be done carefully). Cyclohexane (500 ml), EtOAc (400 ml) and Water (1.21) were added to the reaction mixture, the mix was stirred at 20° C for 15 min. The phases were separated, the organic layer was washed with additional water (400 ml), dried over Na2SC>4 filtered and concentrated to dryness under reduced pressure to afford 113.2 g of crude (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6-(trityloxymethyl)tetrahydropyran as orange oil. UPLC-MS: Method A rt = 1.73 min, ESI+ [M+Na]+= 729.5 found

[1547] Step 3 - Synthesis of [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl methanol

[1548] Reaction performed under nitrogen: (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6-(trityloxymethyl)tetrahydropyran (113.2 g, crude from step 2) was dissolved in a mixture ofMethanol (100 mL) and Dichloromethane (60 mL). 4-methylbenzenesulfonic acid hydrate (3.85 g, 20.23 mmol) was added at 20° C, pH was checked and was < 4. The mixture was stirred at 20° C for 8 hours. UPLC-MS showed complete conversion. The reaction was neutralized with triethylamine (2.82 mL, 20.23 mmol) and the solvent was concentrated to dryness under reduced pressure (T Bath 35° C). The crude was extracted with Dichloromethane (500 ml), washed with H2O and concentrated to dryness. The oil obtained was purified by flash chromatography using Cy / EtOAc 90:10 to 20:80 as eluent, column Biotage Sfar 340 g, fractions with product were collected and concentrated to afford [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl]methanol (49 g, 105.48 mmol, 89.7% yield for two steps) as yellow oil. UPLC-MS: Method A, rt = 1.31 min, ESI+ [M+Na]+= 487.27 found. 'H NMR (400 MHz, Chloroform- ) 8 7.41 - 7.29 (m, 15H), 4.97 (d, J= 11.0 Hz, 1H), 4.81 (d, J= 12.3 Hz, 1H), 4.76 - 4.68 (m, 3H), 4.66 (s, 2H), 4.03 -3.90 (m, 2H), 3.90 - 3.75 (m, 3H), 3.64 (ddd, J= 8.2, 4.6, 3.0 Hz, 1H), 3.33 (s, 3H), 2.01 (dd, J = 7.5, 5.7 Hz, 1H).

[1549] Step 4 - Synthesis of (2S,3S,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxane-2-carbaldehyde

[1550] [(2R,3R,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]methanol (6.0 g, 12.92 mmol) was dissolved in Dichloromethane (35 ml) at 20° C, then Dess-Martin periodinane (3.7 g, 23.25 mmol) was added, the mix was stirred for 2 hours at 25° C, reaction completed (check by NMR), mix was concentrated to small volume, rinsed with AcOEt-Cy 1: 1 (60 ml), the white precipitate was removed by filtration and the solution was collected, concentrated, stripped 3 times with Toluene and resulting crude was purified by chromatography on a Biotage Sfar 10 g, Cy-AcOEt 100:00 to 40:60 to afford (2S,3S,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxane-2-carbaldehyde (5.4 g, 11.67 mmol, 90.4 % yield) as pale yellow oil. Store at -20° C, the aldehyde intermediate was stripped with Toluene three times just before use.

[1551] Step 5 - Synthesis of [(E)-2-[(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl]vinyl] phosphonic acid

[1552] Reaction performed under Nitrogen: to a suspension of Sodium Hydride, 60% w / w dispersion in mineral oil (0.63 g, 15.76 mmol) in anhydrous toluene (35 mL) cooled at 10 °C was added dropwise 1 -[di ethoxy phosphorylmethyl (ethoxy)phosphoryl]oxy ethane (5.4 g, 18.74 mmol, caution: H2 evolution), the mixture was warmed to 20° C and stirred for 10 min. (2S,3S,4S,5S,6S)-6-methoxy-3,4,5-tris(phenyl methoxy)oxane-2-carbaldehyde (5.4 g, 11.67 mmol) was added to this mixture and stirred at 20 °C for 1 hour. The reaction mixture was diluted with CH2CI2 (50 ml) and quenched with distilled water (30 ml). The organic layer was extracted again with CH2CI2 (50 ml), organic phases were collected and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (10% to 100% ethyl acetate / hexanes) on a Biotage Sfar 25 g to afford [(E)-2-[(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl]vinyl] phosphonic acid as colourless syrup (5.1 g, 73.2 % yield). UPLC-MS: Method A, rt = 1.41 min, ESI+ [M+H]+= 597.25 found. 'HNMR (400 MHz, Chloroform-d) 87.39 - 7.27 (15 H, m), 6.96 (1 H, ddd, J = 22.1, 17.2, 4.3 Hz), 6.12 (1 H, ddd, J = 21.2, 17.5, 1.8 Hz), 4.88 and 4.59 (2 H, AMq, J = 10.6 Hz), 4.77 and 4.70 (2 H, ABq, J = 12.4 Hz), 4.73 (1 H, s), 4.63 (2 H, s), 4.14 - 4.03 (5 H, m), 3.90 (1 H, dd, J = 9.3, 3.0 Hz), 3.81 - 3.77 (1 H, m), 3.72 (1 H, t, J = 9.5 Hz), 3.29 (3 H, s), 1.31 (6 H, t, J = 7.1 Hz).

[1553] Step 6 - [(E)-2-[(2R,3R,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]ethenyl]phosphonic acid

[1554] This intermediate was used as starting material for Compound 2 preparation.

[1555] Reaction performed under nitrogen atmosphere: (2R,3R,4S,5S,6S)-2-[(E)-2-diethoxyphosphorylethenyl]-6-methoxy-3,4,5-tris(phenylmethoxy)oxane (3.5 g, 5.87 mmol) was dissolved in MeCN (35 mL) then Pyridine (0.76 mL, 9.39 mmol) was added at 20 °C, to this solution Bromotrimethylsilane (6.29 g, 41.06 mmol) was added and the mixture was stirredat 20 °C for 2h. The reaction mixture was cooled to 0 °C and Pyridine (1.23 mL, 15.25 mmol) followed by Water (4.44 mL, 246.38 mmol) were added. After 2 h the reaction mixture was diluted with CH2CI2 (80 ml) and 1 M HC1 (40 mL). The organic layer was collected and the aqueous layer was extracted again with CH2CI2 (50 ml), the organic phases were concentrated under reduced pressure to afford [(E)-2-[(2R,3R,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2- yl]ethenyl]phosphonic acid, 3.1 g of crude used in the next step without purification. UPLC-MS: Method A, rt = 1.27 min, ESI+ [M+H]+= 541.23 found, ESI-[M+H]- = 539.46 found.Example 1. Synthesis of Isopropyl (2S)-2-[[phenoxy-[[(2R,3S,4S,5S,6S)-3,4,5- trihydroxy-6-methoxy-tetrahydropyran-2-yl]methoxy]phosphoryl]amino]propanoate (Compound 1)

[1556] Steps 1 and 2: A mixture of [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2- yl]methanol (2.0 g, 4.31 mmol) was added dropwise to a solution of di chlorophosphoryloxybenzene (999.15 mg, 4.74 mmol) in Dichloromethane (50 mL) at 0° C under Nitrogen. The mixture was stirred at 0° C for 10 min then 4-DMAP (525.97 mg, 4.31 mmol) and TEA (5,97 ml) were added, the mix was let to warm to 20 °C and stirred for 3 hours. UPLC-MS reaction completed. The mix was concentrated to dryness and dissolved in acetonitrile (50 ml), to this mixture isopropyl (2S)-2-aminopropanoate hydrochloride (2.89 g, 17.22 mmol) was added portion wise followed by TEA (10 ml), the mixture was warmed to 50 °C and stirred for 10 hours. The slurry was concentrated to small volume, water (40 ml) was added and the mixture was extracted with AcOEt (30 ml x 2 times). The combined organic layers were concentrated and purified by silica gel column chromatography (Cy / AcOEt 100:00 to 20:80) to give propan-2-yl(2S)-2-{[phenoxy({[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-m ethoxy oxan-2-yl]methoxy} )phosphoryl]amino}propanoate (790 mg, 1.08 mmol, 25 %yield) as colorless oil. UPLC-MS: Method A rt = 1.49 min, ESI+ [M+H]+=734.07 and [M+Na]+=756.07 found.

[1557] Step 3: Propan-2-yl(2S)-2-{[phenoxy({[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-m ethoxy oxan-2-yl]methoxy} )phosphoryl]amino}propanoate (790 mg) was dissolved in EtOH (10 ml) and AcOEt (10 ml), Pd / C 10% (70 mg, wet 50%) was added. The mixture was stirred under Hydrogen atmosphere (7 Bar) for 12 h, NMR Check: reaction completed The reaction mixture was filtered over a plug of celite, the solution was concentrated to dryness. Crude material was loaded over a Biotage KP-Sil 25 g and eluted with DCM / MeOh from 100:00 to 80:20 in 10 CV, fraction with product were collected and concentrated to afford 175 mg of isopropyl (2S)-2-[[phenoxy-[[(2R,3S,4S,5S,6S)-3,4,5- trihydroxy-6-methoxy-tetrahydropyran-2-yl]methoxy]phosphoryl]amino]propanoate (34.3 % yield, purity >95%) as a diastereomeric mixture. UPLC-MS: Method A, rt = 0.77 min, ESI+ [M+H]+= 464.11 found. 'H NMR (400 MHz, Methanol^) 67.39 - 7.33 (m, 2H), 7.28 - 7.23 (m, 2H), 7.19 (t, J= 7.4 Hz, 1H), 5.03 - 4.95 (m, 1H), 4.66 (m, 1H), 4.46 (dd, J= 11.1, 6.2 Hz, 1H), 4.00 - 3.90 (m, 1H), 3.81 (m, 1H), 3.68 (s, 3H), 1.35 (d, J= 7.2, 3H), 1.24 (m, 6H).Example 2. Synthesis of Propan-2-yl(2S)-2-{[phenoxy({2-[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]ethyl}) phosphoryl] amino} propanoate (Compound 2)CHS

[1558] Step 1: [(E)-2-[(2R,3R,4S,5S,6S)-6-methoxy-3,4,5-tris(phenylmethoxy)oxan-2-yl]ethenyl]phosphonic acid (1.8 g, 3.33 mmol) was dissolved in DCM (18 mL), the mixture was cooled to 0° C then oxalyl chloride (1.14 mL, 13.32 mmol) was added dropwise. The mixture was heated to 35° C for 2 h, reaction completed (check with MeOH). The mix was concentrated to dryness, then rinsed with Acetonitrile (15 ml), DIPEA (3.5 ml) followed by phenol (1.25 g, 13.32 mmol) were added at 20° C, reaction check by UPLC after Ih: reaction completed. The mixture was diluted with DCM (50 ml) and washed with water (50 ml). The organic layer was collected, concentrated and the crude was purified by chromatography Biotage KP-Sil 25 g Cy / AcOEt 90:10 to 20:80, fractions with product were collected and concentrted to afford (2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-2-[(E)-2-diphenoxyphosphorylvinyl]-6-methoxy -tetrahydropyran (820 mg, 35.5 % yield) as a pale yellow oil. UPLC-MS: Method A, rt = 1,51 min, ESI+ [M+H]+= 693.08 and [M+Na]+= 715.03 found.

[1559] Step 2: (2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-2-[(E)-2-diphenoxyphosphorylvinyl]-6-methoxy-tetrahydropyran (820 mg, 1.18 mmol) was dissolved in Acetonitrile (10 ml), water was added (3 ml) followed by Lithium hydroxide monohydrate (139.73 mg, 3.33 mmol), the mixture was stirred at 20° C for 18 h, UPLC-MS showed reaction completion, the mix was concentrated to small volume, HC1 1 M was added until pH = 2 was reached, the white precipitated was collected by filtration and dried overnight at 30° C under high vacuum to afford phenoxy-[(E)-2-[(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl]vinyl]phosphinic acid ( 520 mg, 0.843 mmol, 71.1 % yield). UPLC-MS: Method A, rt= 1,37 min, ESI+ [M+H]+= 617.06 found.

[1560] Step 3: Phenoxy[(lE)-2-[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxyoxan-2-yl]ethenyl] phosphinic acid (520 mg, 0.843 mmol) was dissolved in Dichloromethane (5 ml), the mixture was cooled to 0° C then oxalyl chloride (0.142 mL, 1.665 mmol) was added. The mixture was heated to 35° C for 2 h, reaction completed (check with MeOH). The mix was concentrated to dryness, then rinsed with Acetonitrile (5 ml), DIPEA (1.5 ml) followed by isopropyl (2S)-2-aminopropanoate hydrochloride (356 mg, 2.12 mmol) and 4- DMAP (102 mg). The mix was stirred at 55° C for 2 h, reaction check by UPLC showed reaction completion. The mix was concentrated and the crude was purified by chromatography KP-Sil 50 g, Cyclohexane / AcOEt 90:10 to 80:20 in 15 CV, fractions with product were collected and concentrated to afford propan-2-yl(2S)-2- ({phenoxy[(lE)-2-[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxyoxan-2-yl]ethenyl]phosphoryl}amino)propanoate as a pale yellow oil (212 mg, 34,3 % yield). UPLC-MS: Method A, rt = 1,48 min, ESI+ [M+H]+= 730.09 and [M+Na]+= 752.13 found.

[1561] Step 4: Propan-2-yl(2S)-2-({phenoxy[(lE)-2-[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxyoxan-2-yl]ethenyl]phosphoryl}amino)propanoate (212 mg, 0.290 mmol) was dissolved in EtOH (5 ml) and AcOEt (5 ml), Pd / C 10% (30 mg, wet 50%) was added. The mixture was stirred under Hydrogen atmosphere (7 Bar) for 12 h, NMR Check: reaction completed. The reaction mixture was filtered over a plug of celite, the solution was concentrated to dryness dissolved in MeOH (2 ml) and loaded over a Biotage KP-Sil 2g and eluted with DCM-MeOH 8:2 (40 ml), the solution was concentrated to afford propan-2-yl(2S)-2-{[phenoxy({2-[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]ethyl}) phosphoryl]amino}propanoate (purity >95%, 121 mg, 90.5 % Yield). UPLC-MS: Method A, rt = 0.77 min, ESI+ [M+H]+= 462.16 and [M+Na]+= 484.14 found. 'H NMR (400 MHz, Deuterium Oxide) 87.41 (td, J= 7.9, 3.6 Hz, 2H), 7.25 (dt, J= 8.1, 4.0 Hz, 1H), 7.21 - 7.15(m, 2H), 5.03 - 4.80 (m, 1H), 4.44 - 4.28 (m, 1H), 3.96 - 3.84 (m, 1H), 3.69 (m, 1H), 3.60 -3.43 (m, 2H), 3.36 (m, 3H), 2.31 -2.00 (m, 2H), 1.91 - 1.72 (m,21H), 1.46 - 1.10 (m, 9H).Example 3. Dose response curves for Compound 1 and Compound 2 in novel object recognition (nOR) and contextual fear conditioning (CFC) in miceMaterials and Methods

[1562] Mice

[1563] All the studies were performed on adult male and female C57BL / 6J mice (Jackson Laboratory, Maine, USA) at approximately 8-10 weeks of age at the start of experiments. Mice were group-housed on a 12:12 light / dark cycle with ad libitum access to food and water. All experiments were carried out during the light cycle. Mice were handled for 2-3 min / day for 5 days before their behavioral procedure. Validation and reproducibility of data was ensured by repetitions of experiments conducted on different days and on different groups of mice (n=3-4 / group per experiment) and performed by different experimenters. All retentions were scored in blind to treatment.

[1564] Compound preparations

[1565] On the day of the experiments, compounds were dissolved in 10% dimethyl sulfoxide (DMSO, Sigma-Aldrich, 276855) in 1 mL sterile PBS, pH 7.4 to make a stock solution of the desired concentration. Then, subsequently diluted to the final concentrations (see results) in PBS, pH 7.4 / 1% DMSO. The control vehicle solutions consisted of PBS, pH 7.4 / 1% DMSO. Individual compounds were injected subcutaneously (s.c.) 20 min before each behavioral experiment. Mice were randomly assigned to receive treatment with either a compound or vehicle.

[1566] Novel object recognition test

[1567] Novel object recognition (nOR) was performed as follows: one day before training, mice were placed in a clean square novel arena, free of bedding, for 5 min to allow habituation. The following day, mice were trained in the same arena, now containing two identical objects (Mega Bloks 120) and allowed to explore freely for 3 min. Memory tests were performed at 4 hours (h), at 24 h, and 1 week after training. At testing, the mice were placed back into the same arena, in which one of the objects was replaced by a novel object and allowed them to explore for 5 minutes. Each session was video-recorded and analyzed offline by an observer blind to treatment. Time spent interacting / sniffing each object over the 5 min was recorded in seconds, and memory retention was expressed as the percent index exploration preference for the novel object, relative to the total object investigation [100 * (novel object / novel object + old object in seconds) over 5 min], in seconds over the 5 minutes.

[1568] Contextual fear conditioning

[1569] CFC was carried out as follows: the training session consisted in placing the mice in the conditioning chamber and allowing them to explore it for 2 min. The conditioning chamber consisted of a rectangular Perspex box (30.5 x 24.1 x 21.0 cm) with a metal grid floor (Med Associates). Then, the mice received one footshock (0.70 mA, 2 s), delivered via a constantcurrent scrambler circuit, and remained in the chamber for 1 more minute before returning to the home cage. Tests were performed at 24 hours, 1 week and 2 weeks after training. At testing, given at the desired time as indicated in the experiments, the mice were returned to the conditioning chamber for 3 min, in the absence of a footshock. Freezing behavior, defined as a lack of movement besides heartbeat and respiration, was recorded every ten seconds by an experimenter blind to the training and treatment conditions, and the percentage of time spent freezing across the total number of observations was calculated and expressed in %.Results

[1570] Effect of a dose-response curve of Compounds 1 and 2 in wild type mice trained in the novel object recognition (nOR)

[1571] To establish a dose-response curve for each compound, adult wild type C57 / B6 mice (WT) were injected with 233, 850, or 2500 pg / kg of Compound 1, Compound 2, or vehicle 20 min before the novel object recognition (nOR) test. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc test was used for statistical analyses. The significant effects are indicated. The significant effects are indicated. *p< 0.05; ***p<0.001.

[1572] Dose-response curves for Compound 1 or Compound 2 in nOR are reported in FIGs. 1 and 2 respectively.

[1573] Dose-response curve of an s.c. injection of Compound 1 in WT mice is shown in FIG.1. The experimental schedule is shown above the graph. Mice received an s.c. injection (red arrow) of either vehicle or Compound 1 at the indicated doses of 233, 850, and 2500 pg / Kg, 20 min before nOR training and were tested for memory retention at 4 h, 24 h and 1 week post training. Graphs from left to right show respectively the total exploration time of both objects expressed in seconds during the training session, the % preference of objects during training (Tr), and the % preference for the novel object relative to the familiar object during nOR testing at 4 h, 24 h and 1 week after training. N = 6-8 per group. 2 independent experiments. Data are expressed as mean ± s.e.m. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc tests were used.

[1574] Dose-response curve of an s.c. injection of Compound 2 in WT mice. The experimental schedule is shown above the graph. Mice received an s.c. injection (red arrow) of either vehicleor Compound 2 at the indicated doses of 233, 850, or 2500 pg / kg, 20 min before nOR training and were tested for memory retention at 4 h, 24 h and 1 week post training. Graphs from left to right show respectively the total exploration time of both objects expressed in seconds during the training session, the % preference of objects during training (Tr), and the % preference for the novel object relative to the familiar object during nOR testing at 4 h, 24 h and 1 week after training. N = 6-8 per group. 2 independent experiments. Data are expressed as mean ± s.e.m. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc tests were used. The significant effects are indicated. *p < 0.05, ***p< 0.001.

[1575] Effect of a dose-response curve of Compound 1 in wild type mice trained in contextual fear conditioning (CFC)

[1576] To establish a dose-response curve for Compound 1, adult wild type (WT) mice were injected with 233, 850, or 2500 pg / kg of Compound 1 or vehicle 20 min before training in the CFC. Animals were then tested at 24 h, 1 week and 2 weeks after training session. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc test was used for statistical analyses. The significant effects are indicated. *p< 0.05; **p<0.01.

[1577] Dose-response curves for Compound 1 in CFC are reported in FIG. 3.

[1578] Preparation of intermediate, [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6- methoxy- tetrahydropyran-2-yl] methanol

[1579] A7ep 1 -Synthesis of (2S,3S,4S,5S,6R) -2 -methoxy-6- [ (triphenylmethoxy)methyl oxane - 3,4,5 -triol

[1580] (2R,3S,4S,5S,6S)-2-(hydroxymethyl)-6-methoxyoxane-3,4,5-triol (25.0 g, 128.75 mmol), [chloro(diphenyl)methyl]benzene (35.89 g, 128.75 mmol) and Pyridine (25 mL) were mixed at room temperature, the mixture was heated at 100°C for 30 min. UPLC-Ms reaction completed (check by NMR)

[1581] Dichloromethane (400 ml) was added and the mixture was stirred for 1 h at room temperature, the slurry was washed with NH4C1 aq sat (100 ml x 2) and the organic layer was collected and concentrated to afford an oil, Cyclohexane (150 ml) was added and the mixture was heated under stirring for 1 hour at 65°C, the mixture was let to cool to 20° C and left at20°C for 10 h without stirring. The cyclohexane solution was discarded, the oil was collected and concentrated to afford (2S,3S,4S,5S,6R)-2-methoxy-6- [ (triphenylmethoxy )methyl]oxane-3,4,5-triol as white foam (51 g, 0.117 mol).

[1582] 'H NMR (400 MHz, Chloroform^ / ) 6 7.47 - 7.42 (m, 7H), 7.35 - 7.28 (m, 8H), 4.72 (d, J = 1.6 Hz, 1H), 3.95 - 3.90 (m, 1H), 3.83 - 3.62 (m, 3H), 3.44 (qd, J = 9.8, 5.1 Hz, 2H), 3.38 (s, 3H), 2.70 (d, J = 2.3 Hz, 1H), 2.48 (d, J = 4.9 Hz, 1H), 2.24 (d, J = 4.3 Hz, 1H).

[1583] Step 2 - Synthesis of (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6- ( trityloxymethyl) tetrahydropyranPhOBn

[1584] Reaction performed under Nitrogen: (2S,3S,4S,5S,6R)-2-methoxy-6-(trityloxymethyl) oxane- 3,4,5-triol (51 g, 117 mmol) was dissolved in anhydrous DMF (450 mL) and the mixture was cooled to 0° C. Sodium hydride 60% dispersion in mineral oil (23.37 g, 584.2 mmol) was added portion wise in 1 hour, then the mixture was stirred at 0°C for 30 minutes. Chloromethylbenzene (59.16 g, 467.35 mmol) was slowly added to the reaction mixture, the reaction was stirred 10 minutes at 0° C and allowed to warm up to 20° C. The mixture was stirred at 20° C overnight.

[1585] From UPLC analysis no SM was any longer visible. The mixture was cooled to 5° C, then ice was added portion wise to quench the reaction (very slow addition with considerable effervescence formation, to be done carefully). Cyclohexane (500 ml), EtOAc (400 ml) and Water (1.21) were added to the reaction mixture, the mix was stirred at 20° C for 15 min. The phases were separated, the organic layer was washed with additional water (400 ml), dried over Na2SC>4 filtered and concentrated to dryness under reduced pressure to afford 113.2 g of crude (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6-(trityloxymethyl)tetrahydropyran as orange oil. UPLC-MS: Method A rt = 1.73 min, ESI+ [M+Na]+= 729.5 found

[1586] Step 3 - Synthesis of [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl methanol06n

[1587] Reaction performed under nitrogen: (2S,3S,4S,5R,6R)-3,4,5-tribenzyloxy-2-methoxy-6-(trityloxymethyl)tetrahydropyran (113.2 g, crude from step 2) was dissolved in a mixture of Methanol (100 mL) and Dichloromethane (60 mL). 4-methylbenzenesulfonic acid hydrate (3.85 g, 20.23 mmol) was added at 20° C, pH was checked and was < 4. The mixture was stirred at 20° C for 8 hours. UPLC-MS showed complete conversion. The reaction was neutralized with triethylamine (2.82 mL, 20.23 mmol) and the solvent was concentrated to dryness under reduced pressure (T Bath 35° C). The crude was extracted with Dichloromethane (500 ml), washed with H2O and concentrated to dryness. The oil obtained was purified by flash chromatography using Cy / EtOAc 90:10 to 20:80 as eluent, column Biotage Sfar 340 g, fractions with product were collected and concentrated to afford [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2-yl]methanol (49 g, 105.48 mmol, 89.7% yield for two steps) as yellow oil. UPLC-MS: Method A, rt = 1.31 min, ESI+ [M+Na]+= 487.27 found.1HNMR(400 MHz, Chloroform- d) 87.41 - 7.29 (m, 15H), 4.97 (d, J= 11.0 Hz, 1H), 4.81 (d, J= 12.3 Hz, 1H), 4.76 - 4.68 (m, 3H), 4.66 (s, 2H), 4.03 - 3.90 (m, 2H), 3.90 - 3.75 (m, 3H), 3.64 (ddd, J= 8.2, 4.6, 3.0 Hz, 1H), 3.33 (s, 3H), 2.01 (dd, J= 7.5, 5.7 Hz, 1H).Example 4. Synthesis of Propan-2-yl (2S)-2-[({[(2S)-l-oxo-l-(propan-2-yloxy)propan-2-yl]amino}({[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methoxy})phosphoryl)amino]propanoate (Compound Bl)

[1588] Steps 1 and 2: A mixture of [(2R,3R,4S,5S,6S)-3,4,5-tribenzyloxy-6-methoxy-tetrahydropyran-2- yl]methanol (1.0 g, 2.15 mmol) and TEA (283.17 mg, 2.8 mmol) was added dropwise to a solution of Phosphorus(V) oxychloride (0.26 mL, 2.8 mmol) in DCM (100 mL) at -78°C under Nitrogen. The mixture was stirred at -78° C for 30 min, the mix was let to warm to 20° C over 3 h. The mix was concentrated and Acetonitrile (15 ml) followed by isopropyl (2S)-2-aminopropanoate hydrochloride (1.44 g, 8.61 mmol) were added, the mix was stirred for 10 minutes at 20° C then TEA (6 ml) and DMAP (500 mg) were added into the reaction mixture. After addition the mixture was warmed to 40° C and stirred for 5 h. The reaction mixture was quenched with water (40 ml) and extracted with DCM twice (30 ml). The combined organic layers were dried (Na2SC>4), filtered and concentrated. The residue was purified by silica gel column chromatography (Cyclohexane / EtOAc 90:10 to 10:90) to give propan-2-yl (2 S) -2 - [( { [(2 S)- 1 -oxo- 1 -(propan-2-yloxy)propan-2-yl]amino}({[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxyoxan-2-yl]methoxy})phosphoryl)amino]propanoate (620 mg, 0.804 mmol, 18.68% yield) as colorless oil.

[1589] Step 3: Propan-2-yl (2S)-2-[({[(2S)-l-oxo-l-(propan-2-yloxy)propan-2-yl]amino}({[(2R,3R,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-methoxyoxan-2-yl]methoxy})phosphoryl)amino]propanoate (620 mg, 0.804 mmol) was dissolved in EtOH (10 ml) and AcOEt (10 ml), Pd / C 10% (70 mg, wet 50%) was added. The mixture was stirred under Hydrogen atmosphere (7 Bar) for 12 h, NMR Check: reaction completed. The reaction mixture was filtered over a plug of celite, the solution was concentrated to dryness, crude material was dissolved in DCM (4 ml) and loaded over a Biotage KP-Sil 2g and eluted with DCM-MeOH 7:3 (40 ml), the solution was concentrated to afford 321 mg propan-2-yl (2S)-2-[({[(2S)-l-oxo-l-(propan-2-yloxy)propan-2-yl]amino}({[(2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]methoxy})phosphoryl)amino]propanoate (86.5 Yield, purity >95%). UPLC-MS: Method A, rt = 0.77 min, ESI+ [M+H]+= 501.2 found. 'H NMR (400 MHz, Deuterium Oxide) 64.97 (m, 2H), 4.24 (ddd, J= 11.5, 6.7, 1.9 Hz, 1H), 4.16 - 4.06 (m, 1H), 3.95 - 3.82 (m, 3H), 3.78 - 3.61 (m, 3H), 3.39 (s, 3H), 1.36 (d, J= 7.16 Hz, 6H), 1.24 (m, 12H).Example 5. Dose response curves for Compound Bl in novel object recognition (nOR) and contextual fear conditioning (CFC) in miceMaterials and Methods

[1590] Mice

[1591] All the studies were performed on adult male and female C57BL / 6J mice (Jackson Laboratory, Maine, USA) at approximately 8-10 weeks of age at the start of experiments. Mice were group-housed on a 12:12 light / dark cycle with ad libitum access to food and water. All experiments were carried out during the light cycle. Mice were handled for 2-3 min / day for 5 days before their behavioral procedure. Validation and reproducibility of data was ensured by repetitions of experiments conducted on different days and on different groups of mice (n=3-4 / group per experiment) and performed by different experimenters. All retentions were scored in blind to treatment.

[1592] Compound preparations

[1593] On the day of the experiments, compounds were dissolved in 10% dimethyl sulfoxide (DMSO, Sigma-Aldrich, 276855) in 1 mL sterile PBS, pH 7.4 to make a stock solution of the desired concentration. Then, subsequently diluted to the final concentrations (see results) in PBS, pH 7.4 / 1% DMSO. The control vehicle solutions consisted of PBS, pH 7.4 / 1% DMSO. The compound was injected subcutaneously (s.c.) 20 min before each behavioral experiment. Mice were randomly assigned to receive treatment with either a compound or vehicle.

[1594] Novel object recognition test

[1595] Novel object recognition (nOR) was performed as follows: one day before training, mice were placed in a clean square novel arena, free of bedding, for 5 min to allow habituation. The following day, mice were trained in the same arena, now containing two identical objects (Mega Bloks 120) and allowed to explore freely for 3 min. Memory tests were performed at 4 hours (h), at 24 h, and 1 week after training. At testing, the mice were placed back into the same arena, in which one of the objects was replaced by a novel object and allowed them to explore for 5 minutes. Each session was video-recorded and analyzed offline by an observer blind to treatment. Time spent interacting / sniffing each object over the 5 min was recorded inseconds, and memory retention was expressed as the percent index exploration preference for the novel object, relative to the total object investigation [100 * (novel object / novel object + old object in seconds) over 5 min], in seconds over the 5 minutes.

[1596] Contextual fear conditioning

[1597] CFC was carried out as follows: the training session consisted in placing the mice in the conditioning chamber and allowing them to explore it for 2 min. The conditioning chamber consisted of a rectangular Perspex box (30.5 x 24.1 x 21.0 cm) with a metal grid floor (Med Associates). Then, the mice received one footshock (0.70 mA, 2 s), delivered via a constantcurrent scrambler circuit, and remained in the chamber for 1 more minute before returning to the home cage. Tests were performed at 24 hours, 1 week and 2 weeks after training. At testing, given at the desired time as indicated in the experiments, the mice were returned to the conditioning chamber for 3 min, in the absence of a footshock. Freezing behavior, defined as a lack of movement besides heartbeat and respiration, was recorded every ten seconds by an experimenter blind to the training and treatment conditions, and the percentage of time spent freezing across the total number of observations was calculated and expressed in %.

[1598] Results

[1599] Effect of a dose-response curve of Compound Bl in wild type mice trained in the novel object recognition (nOR)

[1600] To establish a dose-response curve for Compound Bl, adult wild type C57 / B6 mice (WT) were injected with 233, 850, or 2500 pg / kg of Compound Bl or vehicle 20 min before the novel object recognition (nOR) test. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc test was used for statistical analyses. Dose-response curves for Compound Bl in nOR is reported in FIG. 4.

[1601] Dose-response curve of an s.c. injection of Compound Bl in WT mice. The experimental schedule is shown above the graph. Mice received an s.c. injection (red arrow) of either vehicle or Compound Bl at the indicated doses of 233, 850, or 2500 pg / kg, 20 min before nOR training and were tested for memory retention at 4 h, 24 h and 1 week post training. Graphs from left to right show respectively the total exploration time of both objects expressed in seconds during the training session, the % preference of objects during training (Tr), and the % preference for the novel object relative to the familiar object during nOR testing at 4 h, 24 h and 1 week after training. N = 6-8 per group. 2 independent experiments. Data are expressed as mean ± s.e.m. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc tests were used.

[1602] Effect of a dose-response curve of compound Bl in wild type mice trained in contextual fear conditioning (CFC)

[1603] To establish a dose-response curve for Compound Bl, adult wild type (WT) mice were injected with 233, 850, or 2500 pg / kg of Compound Bl or vehicle 20 min before training in the CFC. Animals were then tested at 24 h, 1 week and 2 weeks after training session. One way Analysis of variance (ANOVA) followed by Bonferroni’s posthoc test was used for statistical analyses. The significant effects are indicated, **p<0.01.

[1604] Dose-response curves for Compound Bl in CFC is reported in FIG. 5.

[1605] Dose-response curve of an s.c. injection of Compound Bl in WT mice. The experimental schedule is shown above the graph. Mice received an s.c. injection (red arrow) of either vehicle or Compound Bl at the indicated doses of 233, 850, or 2500 pg / kg, 20 min before CFC training and were tested for memory retention at 24 h, 1 week and 2 weeks post training. Graphs from left to right show respectively the % of freezing during training session (Tr), and the % of freezing at 24 h, 1 week and 2 week after training; N = 6-8 per group. 2 independent experiments. Data are expressed as mean ± s.e.m. One-way analysis of variance (ANOVA) followed by Bonferroni’s post-hoc tests were used. The significant effects are indicated, ** p<0.01.

Claims

CLAIMSWhat is claimed is:

1. A compound of Formula (I’)(I’), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:Xis CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;R1is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;R5is H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;R6is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R7is H or C1-C3 alkyl;alternatively, R5and R7, together with the atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R6, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -0-C(=0)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH, or SH;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

2. A compound of Formula (I”):COOR1R1OOCr3(I”), or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=0)-Rx;each Rxis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;R3is H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;each R5is, independently, H, Ci-Ce alkyl, heterocyclyl, aryl, or heteroaryl;each R7is, independently, H or C1-C3 alkyl;alternatively, R5and R7, together with the adjacent atoms they are attached to, form a heterocyclyl ring;each Ryis, independently, H, Ci-Ce alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;Z is absent or O;wherein R1, R2, R3, R5, R7, Rx, and Ryare each optionally substituted with one or more R, halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -0(R), -COO(R), -N(R)2, -NH-C(=NH)-NH2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl, wherein aryl or heteroaryl is optionally substituted with one or more NH2, OH or SH.each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2.

3. A compound of Formula (I):(I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is CCY^Y2), C(=O), or O;Y1and Y2are, independently, H, OH, halo, or Ci-Ce alkyl;each R1is, independently, H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;each R2is, independently, H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or -(CH2)m-Z-C(=O)-Rx;each Rxis H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl;Z is absent or O;R3is H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, O(Ry), N(Ry)2, SRy, or S(=O)nRy;Ryis H, Ci-Ce alkyl, C2-Ce alkenyl, C2-Ce alkynyl, Cs-Cs cycloalkyl, heterocyclyl, aryl, heteroaryl, or cholesteryl;wherein R1, R2, R3, Rx, and Ryare each optionally substituted with one or more halo, Ci-Ce alkyl, Ci-Ce alkoxy, Ci-Ce haloalkyl, Ci-Ce haloalkoxy, Cs-Cs cycloalkyl, -O(R), -N(R)2, -N(R)-C(=O)-R, -N(R)-C(=O)-N(R)2, -O-C(=O)-O(R), -O-C(=O)-N(R)2, -N(R)-C(=O)-O(R), SR, or S(=O)nR,each R is, independently, hydrogen, Ci-Ce alkyl, Ci-Ce haloalkyl, Cs-Cs cycloalkyl, aryl, or heteroaryl;each m is, independently, 0 or an integer selected from 1 to 10; andeach n is, independently, 1 or 2,provided that:when X is C(Y1)(Y2); Y1and Y2are each H; each R1is iso-propyl, each R2is H; and R3is O(RX); then Rxis not methyl or propargyl; andwhen X is C(YX)(Y2); Y1and Y2are each H; each R1is tert-butyl, each R2is H; and R3is O(RX); then Rxis not 2,4-dimethylphenyl.

4. The compound of any one of the preceding claims, wherein X is O.

5. The compound of any one of the preceding claims, wherein X is C(Y1)(Y2).

6. The compound of any one of the preceding claims, wherein Y1and Y2are each H.

7. The compound of any one of the preceding claims, wherein R1is Ci-Ce alkyl.

8. The compound of any one of the preceding claims, wherein R1is methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, or tert-butyl.

9. The compound of any one of the preceding claims, wherein R1is methyl, ethyl, n-propyl, iso-butyl, sec-butyl, or tert-butyl.

10. The compound of any one of the preceding claims, wherein each R2is H.

11. The compound of any one of the preceding claims, wherein at least one R2is -(CH2)m- C(=O)-RX.

12. The compound of any one of the preceding claims, wherein m is 0.

13. The compound of any one of the preceding claims, wherein m is 1.

14. The compound of any one of the preceding claims, wherein at least one Rxis Ci-Ce alkyl.

15. The compound of any one of the preceding claims, wherein at least one Rxis methyl.

16. The compound of any one of the preceding claims, wherein R3is H.

17. The compound of any one of the preceding claims, wherein R3is Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

18. The compound of any one of the preceding claims, wherein R3is N(Ry)2, SRy, or S(=O)nRy.

19. The compound of any one of the preceding claims, wherein, R3is O(Ry).

20. The compound of any one of the preceding claims, wherein at least one Ryis Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

21. The compound of any one of the preceding claims, wherein at least one Ryis Ci-Ce alkyl.

22. The compound of any one of the preceding claims, wherein at least one Ryis Ci-Ce alkyl substituted by one of -O(R), -N(R)2, or -N(R)-C(=O)-R.

23. The compound of any one of the preceding claims, wherein R5is H.

24. The compound of any one of the preceding claims, wherein R5is Ci-Ce alkyl.

25. The compound of any one of the preceding claims, wherein R5is H, methyl, iso-propyl, iso-butyl, sec-butyl, -CH2-OH, -CH(-OH)-CH3, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -CH2-COOH, -(CH2)2-COOH, -CH2-SH, -(CH2)2-S-CH3, -(CH2)3-NH-C(=NH)-NH2, -(CH2)4-NH2, -CH2-phenyl, substituted by para-OH, -Cffc-imidazolyl, or -Cffc-indolyl.

26. The compound of any one of the preceding claims, wherein R6is H, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl.

27. The compound of any one of the preceding claims, wherein R6is Cs-Cs cycloalkyl, heterocyclyl, aryl, or heteroaryl.

28. The compound of any one of the preceding claims, wherein R6is aryl or heteroaryl.

29. The compound of any one of the preceding claims, wherein R7is H.

30. The compound of any one of the preceding claims, wherein each Ris, independently, hydrogen, Ci-Ce alkyl, aryl, or heteroaryl.

31. The compound of claim 1, wherein the compound of Formula (F) is Formula (Fa), Formula (I’b), Formula (I’g), or Formula (I’h):or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

32. The compound of claim 1, wherein the compound of Formula (T) is selected from a compound of Formula (I’c), Formula (I’d), Formula (I’e), and Formula (I’f):or a pharmaceutically acceptable salt or solvate thereof.

33. The compound of claim 1, wherein the compound is:or a pharmaceutically acceptable salt or solvate thereof.

34. The compound of claim 2, wherein the compound of Formula (I”) is selected from a compound of Formula (I”a), Formula (I”b), Formula (I”c), or Formula (I”d),or a pharmaceutically acceptable salt or solvate thereof.

35. The compound of claim 2, wherein the compound is Compound Bl(Compound Bl), or a pharmaceutically acceptable salt or solvate thereof.

36. The compound of claim 3, wherein the compound of Formula (I) is selected from a compound of Formula (la), Formula (lb), Formula (Ic), or Formula (Id),or a pharmaceutically acceptable salt or solvate thereof.

37. The compound of claim 3, wherein the compound is5 or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

38. A pharmaceutical composition comprising a compound of any one of the preceding claims and one or more pharmaceutically acceptable excipients.

39. The pharmaceutical composition of claim 38, wherein the one or more pharmaceutically acceptable excipients is selected from the group consisting of: antioxidant, buffering agent, bulking agent, non-aggregating agent, binding agent, filler, diluent, disintegrant, plasticizer, anti-tacking agent, wetting agent, sweetener, colorant, flavorant, pH adjuster, and surfactant.

40. A method of treating a neurodegenerative disease, neurodevel opmental disorder, age-related cognitive impairment, or age-related memory impairment, the method comprising the administration to a subject in need thereof of an effective amount of a compound according to claims 1-37 or a pharmaceutical composition according to claims 38 or 39.

41. The method of claim 40, wherein the neurodegenerative disease is amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease, or Alzheimer’s disease.

42. The method of claim 40, wherein the neurodevelopmental disorder is Angelman syndrome or an autism spectrum disorder.

43. The method of claim 42, wherein the autism spectrum disorder is an autistic disorder, Asperger's syndrome, Fragile X syndrome, a childhood disintegrative disorder,, or pervasive developmental disorder-not otherwise specified.

44. The method of any one of claims 40-43, wherein the compound of Formula (I’), Formula (I”), or Formula (I) is administered via a route selected from the group consisting of oral administration, nasal administration, administration by inhalation, rectal administration, intraperitoneal injection, intravascular injection, subcutaneous injection, transcutaneous administration, and intramuscular injection.

44. A compound of any one of claims 1-37, or a pharmaceutical composition of claim 38 or 39, for use in the treatment of a neurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment.

45. Use of a compound of any one of claims 1-37, or a pharmaceutical composition according to claim 38 or 39, for the preparation of a medicament for the treatment of aneurodegenerative disease, neurodevelopmental disorder, age-related cognitive impairment, or age-related memory impairment.

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