SPHINGOSINE-1-PHOSPHATE RECEPTOR AGONIST AND ANTAGONIST COMPOUNDS CROSS REFERENCE TO RELATED APPLICATION This application claims priority to U.S. Provisional Application Serial No. 60/876,288 filed on December 21,2006 and U.S. Provisional Application Serial No. 60/876,318 filed December 21, 2006, the contents of which are incorporated herein. BACKGROUND OF THE INVENTION Sphingosine-1-phosphate (SIP) is part of the sphingomyelin biosynthetic pathway and is known to affect multiple biological processes. SIP is formed through phosphorylation of sphingosine by sphingosine kinases (SKI and SK2) and it is degraded through cleavage by sphingosine lyase to form palmitaldehyde and phosphoethanolamine or through dephosphorylation by phospholipid phosphatases. It is present at high levels (-500 nM) in serum, and it is found in most tissues. It can be synthesized in a wide variety of cells in response to several stimuli, which include cytokines, growth factors and G protein-coupled receptor (GPCR) ligands. The GPCRs that bind SIP (currently known as the SIP receptors SlPi.5), couple through pertusis toxin sensitive (Gi) pathways as well as pertusis toxin insensitive pathways to stimulate a variety of processes. The individual receptors of the SIP family are both tissue and response specific and therefore are attractive as therapeutic targets. SIP evokes many responses from cells and tissues. In particular, SIP has been shown to be an agonist at all five GPCRs, SIP, (Edg-1), S1P2 (Edg-5), S1P3 (Edg-3), S1P4 (Edg-6) and S1P5 (Edg-8). The action of SIP at the SIP receptors has been linked to resistance to apoptosis, changes in cellular morphology, cell migration, growth, differentiation, cell division, angiogenesis and modulation of the immune system via alterations of lymphocyte trafficking. Therefore, SIP receptors are targets for therapy of, for example, neoplastic diseases, autoimmune disorders and tissue rejection in transplantation. These receptors also share 50-55% amino acid identity with three other lysophospholipid receptors, LPA1, LPA2, and LPA3 of the structurally related lysophosphatidic acid (LPA). GPCRs are excellent drug targets with numerous examples of marketed drugs across multiple disease areas. GPCRs are cell surface receptors that bind hormones on the extracellular surface of the cell and transduce a signal across the cellular membrane to the inside of the cell. The internal signal is amplified through interaction with G proteins which in turn interact with various second messenger pathways. This transduction pathway is manifested in downstream cellular responses that include cytoskeletal changes, cell motility, proliferation, apoptosis, secretion and regulation of protein expression, to name a few. SIP receptors make good drug targets because individual receptors are expressed in different tissues and signal through different pathways, making the individual receptors both tissue and response specific. Tissue specificity of the SIP receptors is desirable because development of an agonist or antagonist selective for one receptor localizes the cellular response to tissues containing that receptor, limiting unwanted side effects. Response specificity of the SIP receptors is also of importance because it allows for the development of agonists or antagonists that initiate or suppress certain cellular responses without affecting other responses. For example, the response specificity of the SIP receptors could allow for an SIP mimetic that initiates platelet aggregation without affecting cell morphology. The physiologic implications of stimulating individual SIP receptors are largely unknown due in part to a lack of receptor type selective ligands. Isolation and characterization of SIP analogs that have potent agonist or antagonist activity for SIP receptors have been limited. \ SIP) for example is widely expressed, and the knockout causes embryonic lethality due to large vessel rupture. Adoptive cell transfer experiments using lymphocytes from SDPt knockout mice have shown that S1P| deficient lymphocytes sequester to secondary lymph organs. Conversely, T cells overexpressing SIP] partition preferentially into the blood compartment rather than secondary lymph organs. These experiments provide evidence that SIP] is the main sphingosine receptor involved in lymphocyte homing and trafficking to secondary lymphoid compartments Currently, there is a need for novel, potent, and selective agents, which are agonists or antagonists of the individual receptors of the SIP receptor family in order to address unmet medical needs associated with agonism or antagonism of the individual receptors of the SIP receptor family. SUMMARY OF THE INVENTION The present invention provides compounds of Formula I (Formula Removed) wherein DisH,N(R5)2orOR6; X is CH, C(CHj) or N; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (C1-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2),-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O- P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R*-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C20)cycloalkyl, or optionally substituted azetidinyl; i R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (C1- CM) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C2o) alkynyl, aryl substituted (C2-CM) alkynyl, aryl, aryl substituted (C1-C20)alkyl, heteroaryl substituted (C2-C20)alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted i arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R1 and R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)aIkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-rC2)alkyl or optionally substituted phenyl; m is 1 or 2; n is 1, 2 or 3; t is 1,2 or 3; and u is 0, 1 or 2; provided that A and D are not both Hat the same time.; and provided the compound is not (Formula Removed)wherein X is CH or N; Y is CH2, NH, N(CH3), S or O. In a second embodiment the invention provides compounds of the foregoing embodiment wherein A is H, -C(O)-OCH3l -C(O)-NR6, CN, C(O)-NHCH3, COOR6, -R4-COOH, or optionally substituted azetidinyl, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C|-C2o) alkenylene, straight or branched (C1-C20) alkynylene; R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C10) alkyl, (C1-C10) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C10) cycloalkyl substituted alkoxy, (C2-C10) alkenyl, aryl substituted (C2-C10) alkenyl, (C2-C10) alkynyl, aryl substituted (C2-C10) alkynyl, aryl, aryl substituted (C1-C10) alkyl, heteroaryl substituted (C1-C10) alkyl, aryl substituted (C1-C10) alkoxy, heteroaryl substituted (C1-C10) alkoxy, (C1-C10) alkyl substituted aryl, arylalkyl and aryl substituted arylalkyl; wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, halo, hydroxy, (Ci-Cio) alkoxy, or CM; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or MR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R1 and R2 are optionally substituted with oxo or halo. In a third embodiment the invention provides compounds according to any of the foregoing embodiments wherein the compound is a formula of Formula la: (Formula Removed) and isomers, stereoisomers, esters, prodrugs, and pharmaceutically-acceptable salts thereof, wherein; X is CH; YisCH2orO; A is -C(O)-OCH3, -COOH, -R4-COOH, -C(O)-NHCH3, or optionally substituted azetidinyl; wherein R4 is straight or branched (C1-C10) alkylene, straight or branched (Ci-Cio) alkenylene, or straight or branched (Ci-Cio) alkynylene; R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C10) alkyl, (C|-Cio) alkoxy, (C3-C10) cycloalkyl substituted alkyl, (C3-C10) cycloalkyl substituted alkoxy, (C2-C,0) alkenyl, aryl substituted (C2-C10) alkenyl, (C2-C10) alkynyl, aryl substituted (C2-C10) alkynyl, aryl, aryl substituted (C1-C10)alkyl, heteroaryl substituted (C1-C10)alkyl, aryl substituted (C1-C10)alkoxy, heteroaryl substituted (C1-C10)alkoxy, (C1-C10)alkyI substituted aryl, arylalkyl and aryl substituted arylalkyl; wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, CF3, halo, hydroxy, (C1-C10) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; and n is 1 or 2. In a fourth embodiment the invention provides compounds according to any of the foregoing embodiments wherein Y is CH2; A is -CH2-COOH, COOH or R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C10) alkyl, (C2-C]0) alkenyl, (C2-C,0) alkynyl and aryl substituted (C1-C10) alkyl; wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, halo, hydroxy, (C1-C10) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen. In a fifth embodiment the invention provides compounds according to any of the foregoing embodiments wherein X is CH; Y is CH2; A is COOH; R1 is (C1-C10)alkyl, (C2-C10)alkenyl or (C2-C10)alkynyl; R2 is H; and m is 1. In a sixth embodiment the invention provides compounds according to any of the foregoing embodiments wherein the compound is (Formula Removed)In a seventh embodiment the invention provides compounds according to the first embodiment wherein YisCH2,O,SorNR3; wherein R3 is hydrogen, or (C1-C10) alkyl; A is H, -CH2OH, -CH2OH,-C(O)-OCH3, -optionally substituted -(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), -CH=CH-O-P(=O)(OR7)(OR7)orCN; R1 and R2 are independently selected from the group consisting of hydrogen, halo, straight or branched (C1-C10) alkyl, (C1-C10) alkoxy, (C3-C10) cycloalkyl substituted alkyl, (C3-CIO) cycloalkyl substituted alkoxy, (C2-Ci0) alkenyl, aryl substituted (C1-C10) alkenyl, (C2-C10) alkynyl, aryl substituted (C1-C10) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted (C1-C10)alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, (C1-C10)alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from straight or branched (C1-C10) alkyl, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; R6 is independently selected from H or optionally substituted (C1-C2)alkyl; R7 is independently selected from H or optionally substituted (C1-C2)alkyl; and u is 1 or 2. In an eighth embodiment the invention provides compounds according to embodiments one and seven wherein the compound is a compound of Formula Ib: (Formula Removed) wherein;XisCHorN; YisCH2,O, SorNR3; wherein R3 is hydrogen, or (CrC2o) alkyl; A is -CH2-OH, optionally substituted -CH2-P(=(O)(OR7)(OR7) or optionally substituted - CH2-O-P(=(O)(OR7)(OR7); R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C20) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C2o) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl and aryl substituted arylalkyl; wherein such R2 groups may be optionally substituted with (CpC^) alkyl, halo, hydroxy, (C1-C20) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or MR8; wherein R8 is hydrogen or (C1-C20) alkyl group; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo. In a ninth embodiment the invention provides compounds of any of the embodiments one, seven and eight wherein X is CH; Y is CH2; A is -CH2OH, optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7) or optionally substituted -(CH2)n-P(=O)(OR7)(OR7); R1 and R2 are independently selected from the group consisting of hydrogen, halo, straight or branched (C1-C10) alkyl, aryl'substituted (C1-C10) alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, (C1-C10)alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indoIizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C10) alkyl, halo and (C1-C10) alkoxy; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R6 is independently selected from H or optionally substituted (Ci-C2)alkyl; and u is 1 or 2. In a tenth embodiment, the invention provides compounds of embodiments one, seven, eight and nine wherein A is -CH2OH or optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7); D is NH2; R1 and R2 are independently selected from the group consisting of hydrogen, optionally substituted (C1-C10) alkyl; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen;; mis 1; and u is 1. In an eleventh emobodiment the invention provides compounds of embodiments one, seven, eight, nine and ten wherein the compound is (Formula Removed) In a twelfth embodiment the invention provides compounds of the formula (Formula Removed)In a thirteenth embodiment the invention provides a pharmaceutical composition comprising a compound of Formula I (Formula Removed) wherein DisH,N(R5)2,orOR6; X is CH, C(CH3) or N; Y is CH2,0, S or NR3; wherein R3 is hydrogen, or straight or branched (C1-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2)rCOOH(-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR* or -R4-COOH, wherein R4 is .straight or branched (Q-Czo) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C2o)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (Ci-Cao) alkyl, (CI-CM) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20 alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-CM) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)alkyI-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; n is 1,2 or 3; t is 1, 2 or 3; and u is 0,1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof and a pharmaceutically acceptable diluent or carrier. In a fourteenth embodiment the invention provides a method of treating a disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of Formula I (Formula Removed)wherein DisH,N(R5)2(orOR6; XisCH,C(CH3)orN; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (Ci-Cio) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2)t-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (CrCzo) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C20)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (d-CM) alkyl, (C|-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-CM) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (CrC20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)aIkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; n is 1, 2 or 3; tis 1,2 or 3; and u is 0,1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. In a fifteenth embodiment the invention provides a method of claim 14 wherein the disorder is rheumatoid arthritis, lupus, Crohn's disease, asthma, diabetes, pain or psoriasis. In a sixteenth embodiment the invention provides a method of treating a central nervous system disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of Formula I wherein DisH,N(R5)2,orOR6; X is CH, C(CH3) or N; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (C1-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2),-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH—P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (CrCzo) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C20)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (C|-C20) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-0-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyI or optionally substituted phenyl; m is 1 or 2; nis 1,2 or 3; t is 1, 2 or 3; and u is 0, 1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. In a seventeeth embodiment the invention provides a method of treating multiple sclerosis comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of any of the foregoing embodiments or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. In an eighteenth embodiment the invention provides a packaged pharmaceutical comprising one or more compounds according to Formula I (Formula Removed) wherein DisH,N(R5)2,orOR6; X is CH, C(CH3) or N; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (C,-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2)rCOOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=0)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C2o)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, ( C1-C20 alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C,-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; n is 1,2 or 3; t is 1,2 or 3; and u is 0, 1 or 2; or a pharmaceutical!y acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof and instructions for use. hi a nineteeth embodiment the invention provides the packaged pharmaceutical according to embodiment eighteen wherein the compound or compounds are present in a therapeutically effective amount. In a twentieth embodiment the invention provides a compound of Formula 2(Formula Removed) In a twenty-first embodiment the invention provides a compound of Formula 3 (Formula Removed)In a twenty-second embodiment the invention provides a compound of Formula Formula 5 In a twenty-fourth embodiment the invention provides a compound of Formula 6 In a twenty-third embodiment the invention provides a compound of Formula (Formula Removed) (Formula Removed) In a twenty-fifth embodiment the invention provides a compound of Formula 7 (Formula Removed)In a twenty-sixth embodiment the invention provides a compound of Formula 8 In a twenty-seventh embodiment the invention provides a compound of Formula 9 (Formula Removed)In a twenty-eighth embodiment the invention provides a compound of Formula 10 (Formula Removed)In a twenty-ninth embodiment the invention provides a compound of Formula 11 (Formula Removed)In a thirtieth embodiment the invention provides a compound of Formula 12 (Formula Removed)In another embodiment, R1 or R2 are independently fluorine or chlorine or fluoro- or chloro-substituted alkyl. In another embodiment, Z is hydroxy or -OPO3H2. In another embodiment, the a-substituted phosphonate is -CHFPO3H2, -CF2PO3H2, -CHOHPO3H2, -C=OPO3H2 or -OPO2SHz. In a further embodiment, the a-substituted phosphonate is -CHFPO3H2, -CF2PO:3H2, -CHOHPO3H2, or-C=OPO3H2. In another embodiment, R1 is hydrogen and R2 is alkyl, akenyl, or alkynyl having 5, 6,7, 8, or 9 carbon atoms. In another embodiment, R1 is hydrogen and R2 is heptyl, octyl, nonyl, -O-heptyl, -O-octyl, or -O-nonyl. In another embodiment, R1 is hydrogen and R2 is -(CH2)n-OCH3, -(CH2)n-OCF3, -O-(CH2)n-OCH3, or -O-(CH2)n-OCF3, where n is an integer from 1-20, preferably 5,6, 7, 8, or 9. In compounds of Formula I, the R2 group may be an ortho, meta or para substituent on the phenyl ring, preferably para. The R1 group may be an ortho, meta or para substituent on the phenyl ring, preferably meta. Preferred embodiments of compounds according to Formula I exhibit greater specificity for particular SIP receptors or greater potency than SIP receptor agonist compounds reported previously. In another aspect, the invention provides a pharmaceutical composition comprising one or more compounds according to Formula I, or pharmaceutically acceptable salts, solvates, hydrates, metabolites, prodrugs or stereoisomers thereof, and a pharmaceutically acceptable diluent or carrier. In a preferred aspect, the invention provides a pharmaceutical composition wherein the compound or compounds are present in a therapeutically effective amount. In a related aspect, the invention provides a pharmaceutical composition wherein the compound or compounds are present in a prophylactically effective amount. In still another aspect, the invention provides a packaged pharmaceutical comprising one or more compounds according to Formula I or pharmaceutically acceptable salts, solvates, hydrates, metabolites, prodrugs or stereoisomers thereof and instructions for use. In one embodiment, the invention provides a packaged pharmaceutical wherein the compound or compounds are present in a therapeutically effective amount. In another embodiment, the invention provides a packaged pharmaceutical wherein the compound or compounds are present in a prophylactically effective amount. DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel compounds of Formula I: (Formula Removed)and isomers, stereoisomers, esters, prodrugs, and pharmaceutically-acceptable salts thereof, wherein; XisCHorN; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or (C1-C10) alkyl; Z is hydroxy, phosphate, phosphonate, or a-substituted phosphonate; R1 is selected from the group consisting of hydrogen, halo, (C1-C20) alkyl, (C1-C20) alkyl substituted with halo, hydroxy, (C1-C20) alkoxy, or CN; and R2 is selected from the group consisting of hydrogen, halo, (C1-C20) alkyl, (C1-C20) alkoxy, (C3-C2o) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C2o) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl and aryl substituted arylalkyl; wherein such R2 groups may be optionally substituted with (C1-C20)) alkyl, halo, hydroxy, (C1-C20) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR4; wherein R4 is hydrogen or (C1-C20) alkyl; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo. Exemplary compounds according to the invention include, e.g., [(1R,3S)-l-Amino-3-(4-oct-l-ynyl-phenyl)"CyclopentyI]-methanol; [(1R,3S)-l-Amino-3-(4-octyl-phenyl)-cyclopentyl]-methanol; {(1R,3S)-l-Amino-3-[4-(3-phenoxy-propyl)-phenyl]-cyclopentyl}-methanol; [(1R,3R)-l -Amino-3-(4-oct-l -ynyl-phenyl)-cyclopentyl]-methanol; {(1R,3R)-I-Amino-3-[4-(4-phenyl-but-l-ynyl)-phenyl] treated with imidazole (160 mg, 2.36 mmol) and triisopropylchlorosilane (181 mg, 0.94 mmol) overnight at room temperature under nitrogen. The reaction was concentrated under reduced pressure and the crude product was purified via flash chromatography using 3 : 2 / heptane : Ethyl acetate as eluant. Fractions containing product were combined and concentrated to afford (S)-l-Phenoxy-propan-2-ol (390 mg, 62 %) as a clear oil. LCMS (Table 1, Method a) m/z: poor ionization; 'H NMR (400 MHz, DMSO-4;) 5. 7.30 (m, 2H), 6.90 (m, 3H), 4.80 (d, 1H), 3.90 (m, 1H), 3.80 (m, 2H), 1.10 (d, 3H) General Procedure R: Reduction of carboxvlic acid A solution of carboxylic acid in an organic solvent (such as tetrahydrofuran or dioxane) (preferably THF) is added dropwise to a stirred solution of borane in THF at 0-50°C, preferably about 23°C under an inert atmosphere. The reaction is stirred at warmed to 20-50°C, preferably room temperature for 1-24 hours. The reaction is then quenched by cautious addition of methanol at 0-50°C, preferably about room temperature. The crude product is concentrated under reduced pressure, taken up in ethyl acetate, washed with water, dried (Na2SO4), filtered, and concentrated Exemplification of General Procedure R: Preparation of 2-(3-Methoxy-phenoxy)-ethanol (Formula Removed)A 250ml three-necked round-bottomed flask equipped with temperature probe and nitrogen bubbler was charged with 1M Borane/THF solution (60.4 ml, 60.4 m mol) and a solution of (3-Methoxy-phenoxy)-acetic acid (5.00 g, 27.4 mmol) in THF (2.0 ml) was added dropwise, maintaining reaction temperature below 30°C. The reaction was allowed to stir at room temperature overnight. The reaction was quenched by dropwise addition of methanol (20 ml) maintaining the reaction temperature below 35°C. The reaction was stirred at room temperature for 4 hours and concentrated under reduced pressure to yield 2-(3-Methoxy-pkenoxy)-ethanol (4.51 g, 98%) as a clear oil which was used without further purification. LCMS (Table 1, Method a) 2.43 min., m/z: 169 (M+H)+;.'H NMR (400 MHz, DMSO-d6) B. 7.15 (m, 1H), 6.48 (m, 3H), 4.81 (t, 1H), 3.94 (t, 2H), 3.71 (s, 3H), 3.68 (m, 2H) General Procedure S: Cbz protection of an amine To the appropriately substituted amine in a suitable organic solvent (preferably acetonitrile) and water mixture (about 1:1 to 8:1 ratio, preferably 4:1 ratio) is added N-(Benzyloxycarbonyloxy)succinimide (preferably 1 equivalent) followed by potassium carbonate (preferably 1 equivalent). The reaction mixture is stirred at ambient temperature for a period of 1 -4 hours (preferably 1 hour). The solvent is then removed and the remaining aqueous slurry is taken up in water and organic solvent (preferably ethyl acetate). The organic layer is washed with brine, dried over MgSO4 and concentrated in vacuo. The resulting crude can be purified by column chromatography to give the desired product. Exemplification of General Procedure S: Preparation of (1R,3R)-methyl l-(benzyIoxycarbonylamino)-3-(4-bromophenyl)cyclopentanecarboxylate (Formula Removed) To (lR,3R)-mRtby\ l-ammo-3-(4-bromophenyl)cyclopentanecarboxylate (1.5 g, 5.03 mmol) in acetonitrile (7.2 ml) and water (1.800 ml) was added N-(Benzyloxycarbonyloxy)succinimide (1.254 g, 5.03 mmol) followed by potassium carbonate (0.695 g, 5.03 mmol). The reaction mixture was stirred for 1 hour ar room temperature. The solvent was removed and the remaining aqueous slurry was taken up in water and ethyl acetate. The organic layer was removed and washed with brine, dried over MgSO4 and concentrated in vacuo. The crude was purified by flash chromatography to yield (lR,3R)-methyl ]-(benzyloxycarbonylamino)-3-(4- bromophenyl)cyclopentanecarboxylate (1.4 g, 3.24 mmol, 64.4 % yield) as an off white gum. LCMS (Table 1, Method b) R, = 3.01 min; m/z: 433.28 (M+H)*. General Procedure T: Cross coupling of an aryl bromide to a boronic acid To a flask charged with an aryl bromide (1 equivalent), a boronic acid (1-3 equivalents, preferably 1 equivalents) and an inorganic base (cesium carbonate or sodium carbonate) (preferably cesium carbonate) (3-8 equivalents, preferably 3 equivalents) is added an organic solvent (such as 1,2-dimethoxyethane, dioxane or DMF; preferably 1,2-dimethoxyethane) and water mixture (about 10:1 to 1:1 ratio; preferably 4:1 ratio). The mixture is degassed before adding a palladium catalyst (such as tetrakis(triphenylphosphine)palladium, l,r-bis(diphenylphosphino)ferrocene palladium dichloride or bis(triphenylphosphine)palladium(II) chloride; preferably l,l'-bis(diphenylphosphino) ferrocene palladium dichloride) (2 - 10 mol %, preferably 5 mol %). The reaction mixture is heated at 100 - 200 °C (preferably about 120 °C) for a period of 20 - 60 minutes (preferably 30 minutes) in a microwave reactor. Upon completion of the reaction, the mixture is concentrated to dryness, dissolved in a suitable organic solvent (such as EtOAc, or DCM), and washed with a saturated aqueous solution of NaHCO3, dried over an appropriate drying reagent (such as MgSO4, or Na2SO4) and concentrated to dryness to give the crude product. The crude product is purified via flash chromatography to afford the desired product. Exemplification of General Procedure T: Preparation of (1R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-vinylphenyl)cyclopentanecarboxy late (Formula Removed)To a 60-mL microwave vial was suspended (1R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-bromophenyl)cyclopentanecarboxylate (1.1 g, 2.54 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.431 g, 2.80 mmol) and Cs2CO3 (2.487 g, 7.63 mmol) in DME (30 ml) and Water (7.50 ml). The reaction vessel was purged with nitrogen for 5 minutes. PdCl2(dppf) (0.186 g, 0.254 mmol) was added and the reaction vessel was purged with nitrogen one more time. The reaction mixture was heated to 120 °C in microwave for 30 minutes. The product ((]R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-vinylphenyl)cyclopeiUanecarboxylate (705 mg, 1.858 mmol, 73.0 % yield)) was isolated by flash chromatography as a lightly colored oil. LCMS (Table 1, Method b) R, = 2.94 min; m/z: 380.43 (M+H)+. General Procedure U: Hvdroboration reaction of an alkene To a stirred and ice-bath cooled solution of ah alkene in an organic solvent (preferably tetrahydrofuran) is added 9-BBN (1-8 equivalents, preferably 4 equivalents) dropwise. The reaction mixture is monitored by TLC to ensure complete conversion to boronate. After the reaction is complete, the ice bath is removed and the reaction is left to stir at ambient temperature for a period of 4 - 24 hours (preferably 12 - 20 hours) under inert atmosphere. The reaction mixture is then cooled to about 0 °C and diluted with an organic solvent (such as methanol). An aqueous sodium hydroxide solution (about 4-12 equivalents, preferably 8 equivalents) and 30% w/v hydrogen peroxide solution (about 4-12 equivalents, preferably 8 equivalents) is then poured into the rection mixture. Stirring is continued for a period of 1 - 8 hours (preferably 2 hours). The solvent is removed under reduced pressure and the resulting crude can be purified by flash chromatography to afford the desired product. Exemplification of General Procedure U: Preparation of (lR,3R)-mettiy\ l-(benzyloxycarbonylamino)-3-(4-(2-hydroxyethyl)phenyI) cyclopentanecarboxylate (Formula Removed)9-BBN (25 ml, 12.50 mmol) was added dropwise to a stirred and cooled solution of (1R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-vinylphenyl)cyclopentanecarboxylate (0.682 g, 1.797 mmol) in THF (15 mL). The reaction mixture was checked by TLC to ensure complete conversion to boronate. Once complete the ice bath was removed and stirring was continued overnight. The reaction mixture was cooled to 0 °C and methanol (20ml) was added. Aqueous NaOH (7.30 ml, 14.59 mmol) and H2O2 (1.522 ml, 14.90 mmol) were poured into the rection mixture. Stirring was continued for 2 hours. The solvent was removed under reduced pressure and the product purified by FCC to afford (]R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-(2-hydroxyethyl)phenyl)cyclopentanecarboxylate (0.507 g, 1.276 mmol, 71.0 % yield) as colorless oil. LCMS (Table 1, Method b) R, = 2.53 min; m/z: 398.30 (M+H)+. General Procedure V; Deprotection of a Cbz group from an amine A Cbz-protected amine dissolved in an organic solvent (such as methanol, ethanol or ethyl acetate; preferably ethanol) is added to a slurry of Pearlman's Catalyst (2 -10 mol %, preferably 5 mol %) in an organic solvent (such as methanol, ethanol or ethyl acetate; preferably ethanol). The hydrogen gas is bubbled through the reaction for about 5 minutes. The reaction is stirred under the atmosphere of hydrogen for a period of 1 - 48 hours (preferably 2-24 hours). The progress of the reaction is monitored via LCMS. The resulting crude reaction mixture is filtered through Celite® and the filtrate is concentrated in vacuo to yield crude product, which can be further purified via column chromatography or used as is for the next step. Exemplification of General Procedure V: Preparation of (lR,3R)-methyl l-amino-3-(4-(2-(3-methoxyphenoxy)ethyl)phenyl)cyclopentanecar boxylate (Formula Removed)A solution of (1R,3R)-methyl l-(benzyloxycarbonylamino)-3-(4-(2-(3-methoxyphenoxy) ethyl)phenyl)cyclopentanecarboxylate (0.266 g, 0.528 mmol) in EtOH (2.0 ml) was added to a slurry of Pearlman's Catalyst (0.019 g, 0.026 mmol) in EtOH (5.28 ml). Hydrogen gas was then bubbled through the reaction mixture for 2-3 minutes. The resulting mixture was stirred under the atmosphere of hydrogen overnight. The crude mixture was filtered through Celite® and the filtrate was concentrated in vacuo to yield (1R,3R)-methyl l-amino-3-(4-(2-(3-methoxyphenoxy)ethyl) phenyl)cyclopentanecar boxylate (157 mg, 0.425 mmol) as colorless oil. LCMS (Table 1, Method b) R, = 1.82 min; m/z: 370.40 (M+H)+. General Procedure W; Synthesis of an alpha-beta unsaturated ketone An organometalic reagent (1-3 equivalents, preferably 1.1 equivalents) is added to a solution of a beta-alkoxy enone in an organic solvent (preferably THF) at about -78 °C-room temperature (preferably 0 °C). Following the addition the reaction mixture is allowed to warm to about room temperature. After Ih IN HC1 is added until a pH of 1 is obtained. The reaction mixture is taken through an aqueous work-up and the crude product can be purified by chromatography. Exemplification of General Procedure W: Preparation of 3-(4-octylphenyl)cyclohex-2-enone (Formula Removed)To a suspension of magnesium (1.477 g, 60.8 mmol) in THF (56 mL) was added 1-bromo-4-octylbenzene (15.00 g, 55.7 mmol). After stirring for about 6h the reaction mixture was added with filtering to a solution of 3-ethoxycycIohex-2-enone (7.10 g, 50.6 mmol) in THF (28.0 mL) at 0 °C. Following the addition the reaction mixture was allowed to warm to room temperature. After Ih IN HC1 was added until a pH of 1 was obtained. The reaction mixture was diluted with Et2O and the organic layer was separated, washed with NaHCO3, and brine, dried with Na2SO4, filtered and concentrated in vacuo. The crude product was purified by chromatography on silica gel (EtOAc/Hep) to provide 3-(4-octylphenyl)cyclohex-2-enone (9.5 g, 33.4 mmol, 65.9 % yield) as a colorless oil. LCMS (Table 1, Method a) R, = 4.53 min; m/z: 285 (M-H)-; IH NMR (400 MHz, DMSO-d6) 8 7.57 (d, 2H), 7.25 (d, 2H), 6.34 (s, IH), 2.76 (dd, 2H), 2.60 (dd, 2H), 2.40 (dd, 2H), 2.03 (dddd, 2H), 1.58-1.55 (m, 2H), 1.27-1.24 (m, 10H), 0.85 (t, 3H). General Procedure X: Addition of an oreanometallic reagent to an ester To a solution of an ester in an organic solvent (preferably THF) at about -78 °C-room temperature (preferably 0 °C) is added an organometallic reagent (2-10 equivalents, preferably 5 equivalents). After about 2h the reaction mixture is quenched with water and the crude product is extracted into a suitable organic solvent (preferably ether). The crude product can be purified by chromatography. Exemplification of General Procedure X: Preparation of 2-((lRr3R)-l-amino-3-(4-octylphenyl)cyclopentyl)propan-2-ol (Formula Removed)To a solution of (lR,3R)-methyl l-amino-3-(4-octylphenyl)cyclopentanecarboxylate (640 mg, 1.931 mmol) in THF (20 mL) at 0 °C was added a 3M solution of methylmagnesium iodide (3.22 mL, 9.65 mmol) in THF. After 2h water was added to the reaction mixture resulting in an emulsion. The reaction mixture was diluted with Et2O (100 mL) and water (100 mL). To the emulsion was added Rochelle's salt (approx. 5g). The resulting emulsion was sonicated for 15 min. The organic layer was removed. The aqueous layer was extracted with Et2O (100 mL) sonicating for 15 min to break up the emulsion. The combined organic layers were dried (Na2SO4) filtered and cone, in vacuo. The crude product was purified by chromatography on silica gel (40 g) eluting with DCM:MeOH:HOAc:H2O (900:90:9:1). The fractions containing the product were combined and concentrated in vacuo. The resulting residue was diluted with water and lyophilized to provide 2-((lR,3R)-l-amino-3-(4-octylphenyl)cyclopentyl)propan-2-ol, Acetic Acid salt (265 mg, 0.677 mmol, 35.1% yield) LCMS (Table 1, Method a) R, = 3.28 min; m/z: 333 (M-H)-; 1H NMR (400 MHz, DMSO-d6) 5 7.15 (d, 2H), 7.08 (d, 2H), 5.30 (bs, 3H), 3.40-3.25 (m, 1H), 2.52-2.50 (m, 2H), 2.20-2.05 (m, 2H), 1.90-1.78 (m, 4H), 1.70-1.60 (m, 1H), 1.51-1.49 (m, 3H), 1.40-1.30 (m, 1H), 1.30-1.25 (m, 10H), 1.17 (s, 6H), 0.85 (t, 3H). General Procedure Y; Conversion of a tertiary alcohol to an alkane To a slurry of silica gel and a lewis acid (preferably copper sulfate hydrate) in an organic solvent (preferably toluene) is added a tertiary alcohol. The reaction mixture is heated to about 50-200 °C (preferably 100 °C). After about 2 days a dehydrating reagent (preferably Na2SO4) is added. After about Iday the reaction mixture is filtered. The resulting alkene is added to a slurry of a metal catalyst (preferably palladium hydroxide on carbon) in an organic solvent (preferably methanol). Hydrogen is bubbled through the solution for about 5 min and an atmosphere of hydrogen is maintained via balloon. After 15h the reaction mixture is filtered and concentrated in vacuo to provide the alkane. Exemplification of General Procedure Y: Preparation of (5R,7R)-7-(4-(7-methyloctyl)phenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (Formula Removed)To a slurry of silica gel (Ig) and copper sulfate hydrate (Ig) in toluene (10 mL) was added (5R,7R)-7-(4-(7-hydroxy-7rmethyloctyl)phenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (230 mg, 0.640 mmol). The reaction mixture was heated to 100 °C. After 2 days Na2SO4 (approx. 500 mg) was added. After an additional Iday at 100 °C the reaction mixture was cooled to room temperature and filtered, rinsing with EtOAc. The resulting alkene was added to a slurry of palladium hydroxide on carbon (4.49 mg, 0.032 mmol) in MeOH (10.00 mL). Hydrogen was bubbled through the solution ' for 5 min and an atmosphere of hydrogen was maintained via balloon. After 15h the reaction mixture was filtered and concentrated in vacua. The crude alkane was purified by chromatography on silica gel (EtOAc/Hep) to provide (5R,7R)-7-(4-(7-methyIoctyl)phenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (120 mg, 0.349 mmol, 54.6 % yield) as a colorless solid. 'H NMR (400 MHz, DMSO-d6) 8 8.06 (s, 1H), 7.13 (d, 2H), 7.08 (d, 2H), 4.26 (d, 1H), 4.19 (d, 1H), 3.23-3.16 (m, 1H), 2.55-2.50 (m, 2H), 2.16-2.00 (m, 3H), 1.85-1.75 (m, 2H), 1.60-1.45 (m, 4H), 1.3-1.2 (m, 6H), 1.15-1.10 (m, 2H), 0.84 (d, 6H). General Procedure Z; Hvdration of an alkvne An alkyne is dissolved in formic acid and heated to about 50-120 °C (preferably 80 °C). After about 4 h the reaction mixture is cooled to room temperature and concentrated in vacua, diluted with water and heated to about 50-120 °C (preferably 80 °C). After about 4h the reaction mixture is purified by RP HPLC. Exemplification of General Procedure Z: Preparation of l-(4-((lR,3R)-3-amino-3-(hydroxymethyl)cyclopentyl)phenyI)-5-phenylpentan-l-one, Acetic Acid salt (Formula Removed) ((lR,3R)-l-amino-3-(4-(5-phenylpent-l-ynyl)phenyl)cyclopentyl)methanol (900 mg, 2.70 mmol) was dissolved in formic acid (20 mL) and heated to about 80 °C. After 4h the reaction mixture was cooled to room temperature, concentrated in vacuo, diluted with water (10 mL) and reheated to about 80 °C. After 4h the reaction mixture was purified by RP HPLC. Concentration of the fractions containing the desired product provided l-(4-((lR,3R)-3-amino-3-(hydroxymethyl)cyclopentyI)phenyl)-5-phenylpentan-l-one, Acetic Acid (320 mg, 0.778 mmol, 28.8 % yield) as an off white foam. LCMS (Table 1, Method a) R, = 2.19 min; m/z: 352 (M-H)-; !H NMR (400 MHz, DMSO-rffi) 6 7.87 (d, 2H), 7.36 (d, 2H), 7.29-7.15 (m, 5H), 3.46-3.35 (m, 1H), 3.32 (dd, 2H), 3.00 (dd, 2H), 2.61 (dd, 2H),2.13-2.08(m, 1H), 1.93-1.76(m, 5H), 1.69-1.60(m,6H), 1.51-1.41 (m, 1H). General Procedure AA: Synthesis of an alkvlcther To a strong base (preferably sodium hydride) 0.5-2 equivalents (preferably 1 equivalent) in a suitable solvent (preferably DMF) is added an alkylating agent 1-5 equivalents (preferably 1.2 equivalent) followed by a solution of an alcohol. After the reaction is substantively complete the reaction mixture is taken through an aqueous work up and purified by chromatography or distillation. Exemplification of General Procedure AA: Preparation of 7-methoxyhept-l-yne (Formula Removed)To a slurry of sodium hydride (7.86 g, 197 mmol) in DMF (100 mL) was added methyl iodide (12.29 mL, 197 mmol) followed by a solution of hept-6-yn-l-ol (24.5 g, 197 mmol) in DMF (50 mL). Following the addition the reaction was monitored by TLC. After 2h additional methyl iodide (6 mL, 50 mmol) was added followed by sodium hydride (1 g, 25 mmol) portions. At Ih intervals additional sodium hydride (1 g, 25 mmol) portions was added until no alcohol remained as indicated by TLC. Et2O (50 mL) and water (100 mL) was added to the reaction mixture and the layers were separated. The organic layer was washed with brine, dried using Na2SO4, filtered and distilled (145-155 °C) to provide 7-methoxyhept-l-yne (18 g, 121 mmol, 61.7 % yield) as a colorless oil. 'H NMR (400 MHz, DMSO-40 8. 3.28 (t, 2H), 3.19 (s, 3H), 2.71 (t, IH), 2.13 (dddd, 2H), 1.51-1.33 (m, 6H). General Procedure BB: Synthesis of an N-arvl prolinol To a microwave reaction vial is added l,4-dibromobutan-2-ol (0.5-2 equivalents, preferably 1.1 equivalent), an aniline (0.5-2 equivalents, preferably 1.0 equivalent), potassium carbonate (0.5-2 equivalents, preferably 1.1 equivalent) and a polar protic solvent (preferably water). The reaction vial is heated in a microwave at (50-200 watts, preferably 100 watt), (50-200 °C, preferably 120 °C, (100-200 psi, preferably 150 psi), (ramp time of 2-10 min, preferably 5 min) and (hold time of 10-30 min, preferably 20 min). After cooling to rt an organic solvent (preferably EtOAc) is added to the reaction mixture. The organic layer is removed and concentrated in vacua. The crude product is purified by flash chromatography on silica gel. Exemplification of General Procedure BB: Preparation of l-(4-octyIphenyl)pyrrolidin-3-ol (Formula Removed)To 10 microwave vials were added l,4-dibromobutan-2-ol (0.375 mL, 2.75 mmol), 4-octylaniline (0.572 mL, 2.5 mmol), potassium carbonate (0.380 g, 2.75 mmol) and water (3 mL). Each vial was heated in a CEM microwave at 100 watt, 120 °C, 150 psi, ramp time 5 min and hold time 20 min. After cooling to room temperature EtOAc (1 mL) was added to each vial. After thorough mixing the organic layers were removed, combined and concentrated in vacuo. The product was purified by flash chromatography on silica gel (eluting with EtOAc/Hep) to provide 1-(4-octylphenyl)pyrrolidin-3-ol (3.7 g, 13.43 mmol, 53.7 % yield) as a white solid which was stored under nitrogen in a sealed flask. LCMS (Table 1, Method a) R, = 4.88 min; m/z: 276 (M-H)'; 'H NMR (400 MHz, DMSO-4,) 5. 6.95 (d, 2H), 6.41 (d, 2H), 4.88 (d, 1H), 4.37 (m, 1H), 3.36 (dd, 1H), 3.3-3.17 (m, 3H), 3.01 (dd, 1H), 2.43 (t, 2H), 2.06-1.98(m, 1H), 1.89-1.84(m, 1H), 1.52-1.47 (m, 2H), 1.29-1.24 (m, 10H), 0.85 (t, 3H). General Procedure CC: Oxidation of an alcohol to the ketone To a solution of an alcohol in DMSO and an organic solvent (preferably toluene) at -10-10 °C (preferably 0 °C) is added a weak organic base (preferably pyridine, 2-5 equivalents, preferably 3.5 equivalents), followed by a carbodiimide (preferably DCC, 1-3 equivalents, preferably 1.75 equivalents), and an organic acid (preferably TFA, 0.5-2 equivalents, preferably 1 equivalents). Following the addition the reaction mixture is allowed to warm to about room temperature. After about 5 h saturated NaCHCO3 is added to the reaction mixture and the suspension was filtered. The filtrate is partially concentrated in vacuo and the resulting dark oil is extracted with heptane. The heptane extracts are purified by silica gel chromatography. Exemplification of General Procedure CC: Preparation of !-(4-octyIphenyI)pyrroIidin-3-one (Formula Removed)To a solution of l-(4-octylphenyl)pyrrolidin-3-ol (3.7 g, 13.43 mmol) in DMSO (50 ml) and Toluene (50.0 ml) at 0 °C was added pyridine (3.80 ml, 47.0 mmol), DCC (4.85 g, 23.51 mmol), and TFA (1.035 ml, 13.43 mmol). Following the addition the reaction mixture was allowed to warm to room temperature. After 5 h saturated NaCHCO3 was added to the reaction mixture and the suspension was filtered. The filtrate was partially concentrated in vacuo and the resulting dark oil was extracted with heptane. The heptane extracts were purified by silica gel chromatography eluting with EtOAc/Hep to provide H4-octylphenyl)pyrrolidin-3-one (3.1 g, 11.34 mmol, 84 % yield) as a colorless solid. 'H NMR (400 MHz, DMSO-d6) 8. 7.03 (d, 2H), 6.61 (d, 2H), 3.61 (s, 2H), 3.56 (t, 2H), 2.66 (t, 2H), 2.47 (t, 2H), 1.55-1.48 (m, 2H), 1.30-1.20 (m, 10H), 0.85 (t, 3H). General Procedure DD; Reductive Amination on a Ketone To a ketone dissolved in a suitable solvent (such as dichloromethane, methanol, tetrahydrofuran, or dimethylformamide, preferably methanol) is added an amine (1-2 equivalents, preferably 1 equivalent), acetic acid (1-5 equivalents, preferably 3 equivalents) and resin-bound sodium cyanoborohydride (1-5 equivalents, preferably 3 equivalents). The reaction mixture is stirred under an inert atmosphere at room temperature for a period of 12 - 72 hours (preferably 48 hours). Reaction is then filtered to remove the resin-bound borohydride and the resin washed 3 x with a suitable solvent (such as dichloromethane, methanol, tetrahydrofuran, or dimethylformamide, preferably methanol). The filtrate is collected, concentrated and chromatographed to give the desired product. Exemplification of General Procedure DD: Preparation of MethyI-[3-(4-octyl-phenyl)-cyclopentyl]-amino}-acetic acid (Formula Removed)To 3-(4-octyl-phenyl)-cyclopentanone (0.200 g, 0.734 mmol) dissolved in methanol (4.0 mL) was added methylamiono-acetic acid (0.065 g, 0.734 mmol), acetic acid (0.125 mL, 2.20 mmol) and resin-bound sodium cyanoborohydride (0.941 g, 2.20 mmol, 2.34 mmol/g loading). The reaction mixture was stirred under an inert atmosphere at room temperature for 72 hours. The reaction was then filtered to remove the resin-bound borohydride and the resin was washed with MeOH (3 x 10 mL). The filtrate was collected, concentrated and purified by by RP-HPLC (A = 50mM ammonium acetate, B = acetonitrile; 30-80% B over 30.0 min (21.0 mL/min flow rate); 21.2 x 250 mm Thermo Hyperprep C18 column, 8 (im particles) to give Methyl-[3-(4-octyl-phenyl)-cyclopentylj-amino)-acetic acid as a white solid (0.112 g, 43%) LCMS (Table 1, Method f) R, = 1.94 min; m/z: 344 (M-H)\ m/z: 346 (M+H)+ TABLES UTILIZING GENERAL PROCEDURES Table A. Examples following general procedures A, B, C, D, E, F, H (Scheme 1) (Table Removed) Table B. Examples following general procedures A, B, C, D, E, F, G, H (Scheme 1) (Table Removed) Table C. Examples following general procedures A, I, J, E, F, H (Scheme 2) Table D. Examples following general procedures A, I, J, E, F, G, H (Scheme 2) able E. Examples (Table Removed) Table G. Examples following general procedures P (Scheme 5) The letters in parentheses below the ester precursors indicate the General Procedure by which the ester was made. (Table Removed) Table H. Examples following general procedures A, I, J, E, F, G, H, K, L, M, N (Scheme 11)Table I. Examples following general procedures A, B, C, D, £, S, T, U, M, V, H (Scheme 7) (Table Removed) Table J. Intermediates prepared following general procedure AA (Scheme 8) Table K. Examples following general procedures BB, CC, B, D, E, H (Scheme 9) (Table Removed) Table L. Examples following general procedures A, I, J, E, H, K, F, M, N (Scheme 10) (Table Removed) Table M. Examples following general procedures D (Scheme 12) The letters in parentheses below the ester precursors indicate the General Procedure by which the ester was made. Table N. Examples following general procedures A, F, G, D (Scheme 13) (Table Removed)Table O. Examples following general procedures A, B, C, D, £, F (Scheme 14) (Table Removed)Table P. Examples following general procedures A, B, C, D, E, F, G (Scheme 15) Table Q. Examples following general procedures A, I, J, E, H, K, L, M, N (Scheme 3) Table R. Examples following general procedures O (Scheme 4) The letters in parentheses below the amino-alcohol precursors indicate the General Procedure by which the amino-alcohol precursor was made. (Table Removed)PREPARATION OF ADDITIONAL MOLECULES (NOT IN TABLES): Preparation ot4-Benzyloxy-N-prop-2-ynyl-butyramide (Table Removed)A solution of 4-BenzyIoxy-butyric acid (l.OOg, 5.15 mmol) and Propargylamine (284 mg, 5.15 mmol) in DMF (10.3 ml) was treated with Diisopropylethylamine (0.90 ml, 5.15 mmol), Hydroxybenzotriazole (788 mg, 5.15 mmol) and EDC (665 mg, 5.15 mmol) at room temperature. The resulting mixture was stirred overnight at room temperature under nitrogen. The reaction was concentrated under reduced pressure and the crude product is taken up in Ethyl acetate, washed with water, dried using Na2SO4, filtered, and concentrated to yield 4-Benzyloxy-N-prop-2-ynyl-butyramide (1.02 g, 86%) as a viscous oil. LCMS (Table 1, Method a) min., /n/z:(M+H)+; 'H NMR (400 MHz, DMSO-d6) 8. 8.24 (broad t, 1H), 7.30 (m, 5H), 4.43 (s, 2H), 3.82 (m, 2H), 3.40 (t, 2H), 3.31 (s, 1H), 2.16 (t, 2H), 1.76 (m, 2H) Preparation of 2-(3-Benzyloxy-propyl)-5-methyl-oxazole (Table Removed)A solution of 4-Benzyloxy-N-prop-2-ynyl-butyramide (500 mg, 2.16 mmol) in acetonitrile (22 ml) was treated with Gold (HI) chloride (32.8 mg, 0.108 mmol) at room temperature. The reaction was heated at 50°C for 8 hours then was allowed to stir at room temperature overnight. The reaction was concentrated under reduced pressure and the residue was purified on silica gel using 1 : 1 / heptane : ethyl acetate as eluant. Fractions that contained product were combined and concentrated under reduced pressure to yield 2-(3-Benzyloxy-propyl)-5-methyl-oxazole (405 mg, 81%) as a clear oil. LCMS (Table 1, Method a) min., m/z:(M+H)+; !H NMR (400 MHz, DMSO-d6) 8. 7.32 (m, 5H), 6.67 s, 1H), 4.45 (s, 2H), 3.47 (t, 2H), 2.73 (t, 2H), 2.23 (s, 3H), 1.92 (m, 2H) Preparation of 3-(5-Methyl-oxazol-2-yl)-propan-l-ol (Formula Removed)solution of 2-(3-Benzyloxy-propyl)-5-methyI-oxazole (675 mg, 2.92 mmol) in ethanol (15 ml) containing a suspension of 10% Pd on C (63.9 mg, 0.06 mmol) was hydrogenated overnight at room temperature. The catalyst was removed by filtration through Celite®, then the filtrate was concentrated and the residue was purified on silica gel using 1 : 1 / heptane : ethyl acetate and then ethyl acetate as eluants. Fractions that contained product were combined and concentrated under reduced pressure to yield 3-(5-Methyl-oxazol-2-yl)-propan-l-ol (242 mg, 59%) as an oil. LCMS (Table 1, Method a) 1.85 min., m/z: 142 (M+H)+; !H NMR (400 MHz, DMSO-4,) 8. 6.64 (s, 1H), 4.50 (t, 1H), 3.41 (m, 2H), 2.67 (t, 2H), 2.22 (s, 3H), 1.76 (m, 2H) Preparation of 5-methoxy-pentan-l-ol (Formula Removed)To a flask charged with ((5-methoxypentyloxy)methyl)benzene (4.25 g, 0.0204 mol), palladium on carbon (0.5 g) was added ethanol (40 mL). The mixture was stirred at room temperature under hydrogen (balloon) for 1 hour. The crude mixture was filtered through a pad of Celite®, concentrated, and dried under vacuum to give 5-methoxy-pentan-l-ol (2.40 g, 100%). 'H NMR (400 MHz, DMSO-40 S 4.32 (t, 3H), 3.37 (m, 2H), 3.31 (m, 1H), 3.21 (s, 3H), 1.39-1.49 (m,4H), 1.25-1.32 (m,2H) Preparation of 3-(3-methoxy-phenyI)-propan-l-ol (Formula Removed)A solution of 3-(3-methoxyphenyl)propanoic acid (2.00g, 11.10 mmol) in THF (2.0 mL) was added dropwise to a stirred solution of borane-tetrahydrofuran complex (24.42 mL, 24.42 mmol) so as to maintain reaction temperature below 35 °C. The mixture was allowed to stir at room temperature overnight. Methanol was added dropwise to the stirred mixture until visible reaction had ceased. An additional 20 mL of methanol was added and the reaction was stirred for 4 hours. The crude mixture was concentrated, filtered and purified by silica gel chromatography (1:1 heptane:EtOAc as eiuant). Fractions containing product were combined and concentrated to give 3-(3-methoxy-phenyl)-propan-l-ol as an oil. 'H NMR (400 MHz, DMSO-d6) 8 7.17 (m, 1H), 6.74 (m, 3H), 4.44 (t, 1H), 3.72 (s, 3H), 3.40 (m, 2H), 2.57 (m, 2H), 1.69 (m, 2H) Preparation of 3-(3,5-dimethoxy-phenyl)-propan-l-ol (Formula Removed)A solution of 3-(3,5-dimethoxyphenyl)propanoic acid (2.00 g, 9.51 mmol) in THF (2.0 mL) was added dropwise to a stirred solution of borane-tetrahydrofuran complex (20.93 mL, 20.93 mmol) so as to maintain reaction temperature below 35 °C. The mixture was allowed to stir overnight at room temperature. Methanol was added dropwise to the stirred mixture until visible reaction had ceased. An additional 20 mL of methanol was added and the reaction was stirred for 4 hours. The crude mixture was concentrated, filtered and purified by silica gel chromatography (1:1 heptane:EtOAc as eiuant). Fractions containing product were combined and concentrated to give 3-(3,5-dimethoxy-phenyl)-propan-l-ol as an oil. 'H NMR (400 MHz, DMSO-d6) 8 6.34 (d, 2H), 6.29 (t, 1H), 4.43 (t, 1H), 3.71 (s, 6H), 3.40 (m, 2H), 2.57 (m, 2H), 1.69 (m, 2H). Preparation of 2-(4-fluoro-phenoxy)-ethanol (Formula Removed) A solution of 4-fluorophenol (2.00 g, 17.84 mmol) in DMF (10 mL) was added dropwise to a stirred suspension of NaH in DMF (2.0 mL) at around 10 °C. Ethyl bromoacetate (2.483 mL, 22.30 mmol) was added dropwise and then the reaction mixture was allowed to warm up to room temperature for 4 hours. The solvent was removed under vacuum and the residue was dissolved in methylene chloride and washed 2 times with water, dried over MgSO4, filtered and concentrated to dryness. The crude product was purified on silica gel using (4:1 heptane:EtOAc as eluent) to give ethyl 2-(4-fluorophenoxy)acetate (3.12 g, 95 %). 'H NMR (400 MHz, DMSO-d6) 6 7.09 (m, 2H), 6.94 (m, 2H), 4.84 (t, 1H), 3.94 (t, 2H), 3.69 (m, 2H) Ethyl 2-{4-fluorophenoxy)acetate (3.12g, 15.74 mmol) was dissolved in diethyl ether (50ml) and cooled to about 0 °C. Lithium aluminum hydride (1.792 g, 47.2 mmol) was added in portions while maintaining reaction temperature below 35 °C. The reaction was allowed to stir at room temperature for one hour. The crude reaction was diluted with ether (50 mL) then cooled in an ice bath and quenched by dropwise addition of water (6.1 mL), then 2 M NaOH (12.2 mL), then water (6.1 mL). The mixture was filtered and concentrated. The crude product was purified on silica gel (4:1 heptane:EtOAc as eluant) to give 2-(4-fluoro-phenoxy)-ethanol (1.36 g, 55 %). 'H NMR (400 MHz, DMSO-4s) 8 7.08-7.13 (m, 2H), 6-92-6.96 (m, 2H), 4.84 (t, 1H), 3.95 (t, 2H), 3.69 (m, 2H). Preparation of 4-{2-[4-((1R,3R)-3-amino-3-hydroxymethyl-cycIopentyl)-phenoxy]-ethyI}-phenol (Formula Removed) To a solution of ((1R,3R)-l-amino-3-(4-(4-(benzyloxy)phenethoxy)phenyl)cyclopentyl) methanol (250 mg, 0.599 mmol) in ethanol (10 mL) was added Pd/C 10% (20 mg, 0.188 mmol). The mixture was flushed with hydrogen and hydrogenate with a balloon for about 16 hours. The crude mixture was filtered, concentrated and the residue was triturated with ether. The solid was collected and dried under vacuum at 50 °C to give 4-(2-(4-((1R,3R)-3-amino-3-(hydroxymethyl)cyclopentyl)phenoxy)ethyl)phenol (169 mg, 86 %) as a white solid. LCMS (Table 1, Method b) R, = 1.75 min; m/r. 328 (M+H)+; 'H NMR (400 MHz, DMSCMs) 8 7.10 (m, 4H), 6.81 (dd, 2H), 6.68 (dd, 2H), 4.63 (b, 1H), 4.05 (t, 2H), 3.31 (s, 3H), 2.88 (t, 2H), 1.98-2.07 (m, 1H), 1.77-1.84 (m, 1H), 1.30-1.65 (m, 5H). Preparation of 4-((7S)-3-methyl-2,4-dioxo-13-diazaspiro[4.4]nonan-7-yl)benzonitrile (Formula Removed)A suspension of (7S)-7-(4-bromophenyl)-3-methyI-l,3-diazaspiro[4.4]nonane-2,4-dione (General procedures A, B, C) (0.500 g, 1.547 mmol) in anhydrous NMP (4.00 ml) was degassed by evacuating the reaction vial then refilling with N2 a couple of times. To this suspension was added zinc (1.012 mg, 0.015 mmol), dppf (0.027 g, 0.048 mmol), zinc cyanide (0.145 g, 1.238 mmol), and Pd2(dba)3 (0.021 g, 0.023 mmol) at ambient temperature. The resulting mixture was heated to 120 °C for about 16 hours. The crude material was filtered through Celite®. The filtrate was taken up in water (70mL) and ethyl acetate (lOOmL). The organic phase was washed with water (50mL x 2) and brine (50mL), dried (MgSO4) and concentrated to yield 4-((7S)-3-methyl-2,4-dioxo-l,3-diazaspiro[4.4]nonan-7-yl)benzonitrile (0.44 g, 0.20 mrnol) as light brown solid. LCMS (Table 1, Method a) R, = 2.04 min; m/Z: 270.15 (M+H)+; 'H NMR (400 MHz, Methanol-d4) 8 ppm 3.52-3.39 (m, 1H), 2.10-1.85 (m, 3H), 2.31-2.15 (m, 3H), 7.69-7.64 (m, 2H), 7.50 (t, J = 8.45 Hz, 2H), 2.96 (d, J = 2.91 Hz, 3H), 2.59-2.34 (m, 1H). Preparation of (Z)-N'-hydroxy-4-{(7S)-3-methyl-2,4-dioxo-l,3-diazaspiro[4.4]nonan-7-i yljbenzimidamide (Formula Removed)4-((7S)-3-methyl-2,4-dioxo-l,3-diazaspiro[4.4]nonan-7-yl)benzonitrile (0.88 g, 3.27 mmol) was suspended in ethanol (20 ml). To this was added hydroxylamine (0.240 ml, 3.59 mmol) as 50% weight solution in water, and the reaction was heated to 60 °C under an atmosphere of nitrogen for about 20 hours. The reaction mixture was left to cool down to ambient temperature. Solvent was partially removed. The resulting white precipitate was filtered, rinsed with cold ethanol and vacuum-dried to afford (Z)-N'-hydroxy-4-{(7S)-3-methyl-2,4-dioxo-l,3-diazaspiro[4.4Jnonan -7-yljbenzimidamide as light brown solid (1.12 g, 3.20 mmol). LCMS (Table 1, Method a) R, = 1.47 min; m/r. 303.33 (M+H)+; 'H NMR (400 MHz, Methanol-d4) 8 ppm 2.96 (d, 7 = 3.16 Hz, 3H), 2.43-2.33 (m, 1H), 3.39 (ddd, J = 18.31, 11.00, 7.39 Hz, 1H), 7.36-7.30 (m, 2H), 7.58 (d, J = 8.23 Hz, 2H), 2.29-1.87 (m, 6H). Preparation of (7S)-7-(4-(5-(4-isobutylphenyl)-l,2,4-oxadiazol-3-yl)phenyl)-3-methyl-lr3-diazaspiro[4.4]nonane-2,4-dione (Formula Removed) A solution of 4-isobutylbenzoic acid (0.130 g, 0.728 mmol), EDC (0.139 g, 0.728 mmol) and HOBt hydrate (0.111 g, 0.728 mmol) in DMF (1.0 ml) was stirred at ambient temperature for 1 - 1.5 hours. To the mixture was added (Z)-N'-hydroxy-4-{(7S)-3-methyl-2,4-dioxo-l,3-diazaspiro[4.4]nonan-7-yl}benzimidamide (0.200 g, 0.662 mmol) as solution in 1.0 ml DMF at ambient temperature. The resulting mixture was heated to about 140 °C for additional 2 hours. Solvent was removed in vacuo. The crude product was purified on a Prep HPLC system using 20 -99% 50 mM NH,OAc buffer in acetonitrile at 81 mL/min to afford (7S)-7-(4-(5-(4-isobutylphenyl)-l,2,4-oxadiazol-3-yl)phenyl)-3-methyl-l,3-diazaspiro[4.4]nonane-2,4-dione (0.062 g, 0.139 mmol) as light brown solid. LCMS (Table 1, Method a) R, = 4.48 min; m/z: 445.39 (M+H)+; 'H NMR (400 MHz, Methanol-d4) 8 ppm 7.53-7.39 (m, 4H), 8.15-8.06 (m, 4H), 3.52-3.41 (m, 1H), 2.98 (d, J = 3.39 Hz, 3H), 2.61 (d, J = 7.22 Hz, 2H), 2.46-2.37 (m, 1H), 2.35-2.20 (m, 3H), 2.07-1.90 (m, 3H), 0.95 (d, J = 6.62 Hz, 6H). Preparation of (3S)-l-amino-3-(4-(5-(4-isobutylphenyl)-l,2,4-oxadiazo!-3-yl)phenyI)-Af-methylcyclopentanecarboxamide (Formula Removed) (7S)-7-(4-(5-(4-isobutylphenyl)-l,2,4-oxadiazol-3-yl)phenyl)-3-methyl-l,3-diazaspiro[4.4]nonane-2,4-dione (0.052 g, 0.117 mmol) was taken up in dioxane (1.0 ml). To this was added sodium hydroxide (1.0 ml, 2.000 mmol) as 2M solution. The resulting suspension was heated to 120 °C for about 70 hours, during which more sodium hydroxide solution was added to push the hydrolysis to completion. Heating was stopped and the reaction mixture was concentrated in vacuo. The resulting material was brought up in 1 - 2 mL DMSO and filtered. The filtrate was purified on a Prep HPLC system using 30 - 100% acetonitrile in 50 mM NtUOAc buffer at 21 mL/min to yield (3S)-l-amino-3-(4-(5-(4-isobutylphenyl)-l,2,4-oxadiazol-3-yl)phenyl)-N-methylcyclopentanecarboxamide (0.017 g, 0.041 mmol) as off-white solid. LCMS (Table 1, Method b) R, = 1.76 min; m/z: 419.24 (M+H)+; 'H NMR (400 MHz, CDC13) 8 ppm 8.11 (dd, J = 9.86, 8.34 Hz, 4H), 7.44 (d, J = 8.17 Hz, 2H), 7.32 (d, J = 8.16 Hz, 2H), 7.80-7.71 (m, 1H), 3.56-3.36 (m, 1H), 2.86 (d, J = 4.81 Hz, 3H), 2.65-2.52 (m, 4H), 2.35-2.23 (m, 1H), 2.05-1.86 (m, 4H), 1.65-1.55 (m, 1H), 0.94 (d, J = 6.61 Hz, 6H), 1.34-1.17 (m, 1H). Preparation of 2-(l-amino-3-(4-octylphenyl)cyclopentyl)acetic acid (Formula Removed)3-(4-Octyl-phenyl)-cycIopentanone, malonic acid (0.076 g, 0.734 mmol), ammonium acetate (0.057 g, 0.734 mmol) were suspended in the mixture of ethanol (1.50 mL, 25.7 mmol) and methanol (0.50 mL, 12.36 mmol) in a 15-mL, 2-necked round-bottomed flask equipped with a condenser. The heterogeneous mixture was heated to reflux at 80 °C for about 24 hours. Heating was removed. The crude mixture was taken up in dichloromethane/water mixture (20 mL/20 mL). The resulting fine suspension was filtered, washed several times with water and dichloromethane, and vacuum-dried to yield 2-(l-amino-3-(4-octylphenyl)cyclopentyl)acetic acid (0.020 g, 0.060 mmol) as off-white solid. LCMS (Table 1, Method b) R, = 1.70 min; m/z: 332.30 (M+H)+; 'H NMR (400 MHz, DMSO-d6) 5 ppm 8.48 (d, J = 18.37 Hz, 3H), 7.17 (d, J = 8.01 Hz, 2H), 7.06 (d, J = 7.89 Hz, 2H), 3.54-3.00 (m, 1H), 2.85 (d, J = 10.82 Hz, 2H), 2.49-2.44 (m, 2H), 2.32-2.17 (m, 1H), 2.11-1.59 (m, 5H), 1.48 (s, 3H), 1.20 (d, J = 11.44 Hz, 10H), 0.80 (t, / = 6.72, 6.72 Hz, 3H) Preparation of hept-6-yn-l-ol (Formula Removed) To a round bottom flask equipped with a stirring bar under N2 was added LAH (3.61 g, 95 mmol) and anhydrous diethyl ether (300 ml). The mixture was cooled to 0 °C in an acetonitrile-dry ice bath, a solution of hept-6-ynoic acid (6.00 g, 47.6 mmol) in dry diethyl ether (60.1 ml) was added dropwise with vigorous stirring. The mixture was then allowed to warm to ambient temperature and stirred for an additional hour. Next, 1M HC1 solution (159 ml, 159 mmol) was added dropwise and the reaction mixture was stirred at ambient temperature over the weekend. The layers were then separated. The aqueous layer was back-extracted with diethyl ether (150 mL). The combined organic phase was wash with brine (150mL), dried (MgSO4) and concentrated to yield 5.89 g of colorless liquid. The crude liquid was purified via Analogix FCC system using Biotage RS 330g column, with a gradient of 0-50% ether/pet, ether over 10 min. at 40 mL/min. then held at 50% for 50 min. Fractions containing product were combined and concentrated to yield hept-6-yn-l-ol (4.94 g, 44.0 mmol) as colorless liquid. The title compound was also prepared according to procedure described by B. W. Gung et al, Tetrahedron: Asymmetry, 2005, 16, 3107-3114. ]H NMR (400 MHz, DMSO-d6) 5 ppm 3.66 (t, 3 = 6.32, 6.32 Hz, 2H), 2.26-2.17 (m, 2H), 1.98-1.92 (m, 1H), 1.66-1.53 (m, 4H), 1.53-1.45 (m, 2H) Preparation of 2-(3-methoxy-4-methyIphenyl)ethanol (Formula Removed)2-(3-methoxy-4-methylphenyl)acetic acid (1 g, 5.55 mmol) was dissolved in Tetrahydrofuran (27.7 ml). A solution of borane tetrahydrofuran complex (12.21 ml, 12.21 mmol) was added slowly under nitrogen. The reaction was stirred for about 18 h. Methanol was slowly to quench the reaction. The mixture was rotovapped. More methanol was added. The mixture was rotovapped. This was repeat two more times. The solution was passed through a short pad of silica gel eluting with 1:1 EtOAc/heptane and then rotovapped to give 2-(3-methoxy-4-methylphenyl)ethanol (0.800 g, 4.81 mmol, 87 % yield) as a colorless oil: 'H NMR (400 MHz, CDCIJ 5 ppm 7.07 (dd, 1H), 6.73 (dd, 1H), 6.69 (s, 1H), 3.86 (t, 2H), 3.30 (s, 3H), 2.84 (t, 2H), 2.14 (s, 3H), 1.41 (s, 1H) Preparation of 3-(4-fluoro-3-methoxyphenyl)propan-l-oI (Formula Removed)Ethyl 3-(4-fluoro-3-methoxyphenyl)propanoate (1.019 g, 4.50 mmol) was dissolved in THF (22.52 ml) under nitrogen. A solution of lithium aluminum hydride (4.50 ml, 9.01 mmol) was added slowly. TLC shows reaction done after about 10 min. Water (0.35 mL) was slowed added and then the mixture was stirred for 30 min. 1 N NaOH (1.05 mL) was added and the reaction was stired for 30 min. Additional water was added (0.35 mL) and the solution was stirred and then filtered. The cake was washed with ether and then rotovapped. Ether was added. The solution was dried over magnesium sulfate and then filtered and rotovapped. The solution was passed through silica gel with methylene chloride then ethyl acetate then rotovapped to give 3-(4-fluoro-3-methoxyphenyl)propan-l-ol (0.753 g, 4.09 mmol, 91 % yield) as a colorless oil: 'H NMR (400 MHz, CDC^.8 ppm 6.98 (dd, 1H), 6.80 (dd, 1H), 6.71 (ddd, 1H), 3.89 (s, 3H), 3.68 (t, 2H), 2.68 (t, 2H), 1.94-1.82 (m, 2H), 1.33 (s, 1H) Preparation of 3-(2-methoxyphenyl)propan-l-ol (Formula Removed)3-(2-methoxyphenyl)propanoic acid (1.0 g, 5.55 mmol) was dissolved in THF (27.7 ml). A solution of borane tetrahydrofuran complex (12.21 ml, 12.21 mmol) was added slowly. The reaction was stirred for about 4 h. Methanol was added and the solvents removed. This process was repeated twice. The solution was passed through a short pad of silica gel with 1:1 ethyl acetate/heptane And then rotovapped to give 3-(2-methoxyphenyl)propan-l-ol (0.946 g, 5.69 mmol, 103 % yield) as a colorless oil. 'H NMR (400 MHz, CDCh) 5 ppm 7.19 (dt, 1H), 7.15 (dd, 1H), 6.90 (dt, 1H), 6.86 (d, 1H), 3.84 (s, 3H), 3.60 (t, 2H), 2.73 (t, 2H), 1.92-1.79 (m, 2H), 1.76 (s, 1H), Preparation of 2-(4-methoxy-3-methylphenyl)ethanol (Formula Removed) 2-(4-methoxy-3-methylphenyl)acetic acid (1 g, 5.55 mmol) was dissolved in Tetrahydrofuran (27.7 ml). A solution of borane tetrahydrofuran complex (12.21 ml, 12.21 mmol) was added slowly under nitrogen. The reaction was stirred for about 18 h. Methanol was slowly added to quench the reaction The solution was rotovapped. More methanol was added. The solution was rotovapped. This was repeated twice. The solution was passed through a short pad of silica gel eluting with 1:1 EtOAc/heptane and then rotovapped to give 2-(4-methoxy-3-methylphenyl)ethanol (0.986 g, 5.93 mmol, 107 % yield) as a colorless oil: !H NMR (400 MHz, CDC/0 8 ppm 7.05 (m, 1H), 7.04 (m, 1H), 6.80 (m, 1H), 3.85 (s, 3H), 3.84 (t, 2H), 2.81 (t, 2H), 2.25 (s, 1H), 1.64 (s, 1H) Preparation of 3-(thiophen-2-yl)propan-l-ol (Formula Removed)A solution of borane tetrahydrofuran complex (13.03 ml, 13.03 mmol) was added to THF (29.6 ml). 3-(thiophen-2-yl)propanoic acid (0.100 g, 0.640 mmol) was dissolved in THF (5 mL) and added slowly to the reaction. The solution was stirred overnight. Methanol was added and then the solution was rotovapped. More methanol was added and the solution wasrotovapped. This was repeated once. The solution was passed through a pad of silica gel eluting with ether and then ethyl acetate and then rotovapped to give 3-(thiophen-2-yl)propan-l-ol (0.820 g, 5.77 mmol, 97 % yield) as a light yellow oil: 'H NMR (400 MHz, CDC/3). 5 ppm 7.12 (m, 1H), 6.92 (dd, 1H), 6.81 (m, 1H), 3.71 (t, 1H), 2.95 (t, 1H), 2.02-1.87 (m, 1H) Scheme for preparation of furan analogs outlined below: (Formula Removed)Preparation of l-(4-octylphenyl)but-3-en-l-ol (Formula Removed)4-octylbenzaldehyde (10.0 g, 45.8 mmol) (Aldrich) was dissolved in THF (229 ml) under nitrogen. The reaction was cooled to about 0-5 °C in an ice bath. A solution of allylmagnesium bromide (48.1 ml, 48.1 mmol) (Aldrich) was added slowly and the reaction stirred for about 2 h. The reaction was quenched by the addition of saturated ammonium chloride followed by addition of ethyl acetate. The layers were separated and the aqeous extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to an off-white oil. The residue was dissolved in ether and dried over sodium sulfate and filtered. The solvents were removed under reduced pressure to provide l-(4-octylphenyl)but-3-en-l-ol (11.54 g, 44.3 mmol, 97 % yield) as a light yellow oil: LC/MS (method f) R, = 2.90 min.; MS m/z: 243.21 (M-water)*. Preparation of tert-butyldimethyl(l-(4-octylphenyl)but-3-enyloxy)si]ane (Formula Removed)l-(4-octylphenyl)but-3-en-l-ol (11.5 g, 44.2 mmol) and imidazole (3.16 g, 46.4 mmol) were combined in DMF (221 ml). Tert-butyldimethylchlorosilane (6.66 g, 44.2 mmol) was added and the reaction stirred for about 72 h. The reaction was quench by addition of water and ethyl acetate (500 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (2 x 100 mL). The combined ethyl acetate extracts were washed with 5% LiCl solution (3x). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to provide tert-butyldimethyl(l-(4-octylphenyl)but-3-enyloxy)silane (19.108 g, 51.0 mmol, 115 % yield) as a colorless oil. LC/MS (method f) R, = 5.32,3.89 min.; MS m/z: 243.21 (M-OTBDMS)*. Preparation of 4-(4-octylphenyl)butane-l,2,4-triol (Formula Removed)Tert-butyIdimethyl(l-(4-octylphenyl)but-3-enyloxy)silane (19.108 g, 51.0 mmol) and NMO (7.17 g, 61.2 mmol) were combined in acetone (227 ml) and water (28.3 ml). Osmium tetroxide (32.0 ml, 2.55 mmol) was added and the reaction stirred for about 2 h. TLC in 1:1 EtOAc/heptane showed reaction complete. Sodium thiosulfate (8.06 g, 51.0 mmol) was added and the reaction stirred for about 3 h resulting in a coarse black precipitate. The solution was poured over 150 mL of silica gel and washed product through thoroughly or washed product through?with ethyl acetate until no more product was eluting as shown by TLC (-700 mL EtOAc). The resulting 4-(Tert- butyldimethylsilyloxy)-4-(4-octylphenyl)butane-l,2-diol (14.68 g, 35.9 mmol) and molecular sieves (5 g) (Aldrich) were combined in THF (359 ml) under nitrogen. TBAF (35.9 ml, 35.9 mmol) (Aldrich) was added and the reaction stirred for about 16 h. The mixture was filtered and the solvents evaporated to provide an orange/brown oil. The oil was passed through a pad of silica gel (150 mL) and washed through with ethyl acetate. Product eluted slowly and took almost 2L of EtOAc for all product to elute. The solvents were removed under reduced pressure to provide 4-(4-octylphenyl)butane-l,2,4-triol (12.045 g, 40.9 mmol, 114 % yield) as an orange oil: LC/MS (Purity QC) R, = 3.84,3.89 min.; MS m/z. 294.40, 294.02 (M+H)+. Preparation 5-(4-octylphenyl)tetrahydrofuran-3-ol (Formula Removed)4-(4-octylphenyl)butane-l,2,4-triol (12 g, 40.6 mmol) was dissolved in 1,2-Dichloroethane (815 ml) under nitrogen. p-Toluenesulfonic acid monohydrate (1.55 g, 8.2 mmol) (TCI) was added and the reaction heated at about 50 °C for about 3 h. TLC in 1:1 EtOAc/heptane showed (PMA visualization) reaction complete. The solution was washed with saturated sodium bicarbonate and extract with methylene chloride (2x). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a yellow oil. The resulting oil was chromatographed on 330 g redi-sep column eluting with 20% EtOAc in heptane for 10 min ramping to 50% over 20 min and then holding at 50% until all the product was off (monitor at 223 nm due to weak chromaphore at longer wavelengths). Removed solvent under reduced pressure to provide 5-(4-octylphenyl)tetrahydrofuran-3-ol (7.36 g, 26.6 mmol, 73.3 % yield) as a colorless oil: LC/MS (method A) R, = 3.76 min.; MS m/z: 277.15 (M+H)+. Preparation of 5-(4-octylphenyl)dihydrofuran-3(2H)-one (Formula Removed)5-(4-octylphenyl)tetrahydrofuran-3-ol (1 g, 3.62 mmol) was dissolved in dichloromethane (36.2 ml) in a sealed vial. PCC (3.12 g, 14.47 mmol) (Aldrich) was added and the reaction stirred for about 16 h. The methylene chloride was evaporated and the residue stirred with ethyl acetate. The ethyl acetate was filtered through a pad of silica gel (approx. 50 mL silica) and product eluted with ethyl acetate. This removed most of the brown color. Concentrate and then chromatograph on a 40 g redi-sep column with 20-50% ethyl acetate in heptane. Remove solvent under reduced pressure to provide 5-(4-octylphenyl)dihydrofuran-3(2H)-one (0.839 g, 3.06 mmol, 85 % yield) as a colorless oil: LC/MS(methoda)R, = 4.14min.;MSffz/z: 275.25 (M+H)+. 8-(4-octylphenyI)-7-oxa-l,3-diazaspiro[4.4]nonane-2,4-dione (Formula Removed)5-(4-octylphenyl)dihydrofuran-3(2H)-one (0.8 g, 2.92 mmol) and ammonium carbonate (1.037 g, 13.12 mmol) (Aldrich) were combined in ethanol (12.05 ml) and water (12.05 ml). Potassium cyanide (0.209 g, 3.21 mmol) (Fluka) was added and the reaction heated at about 80 °C for about 16 h. Cool the reaction and add concentrated HC1 until acidic (caution for HCN gas formation). The precipitate was collected by vacuum filtration and washed with water. It was suspended in methylene chloride, filtered, and washed with methylene chloride to provide 8-(4-octylphenyl)-7-oxa-l,3-diazaspiro[4.4]nonane-2,4-dione (0.545 g, 1.582 mmol, 54.3% yield) as a white solid: LC/MS (method A) R, = 4.29 min.; MS m/z: 343.46 (M-H)'. Preparation of 3-amino-5-(4-octylphenyl)tetrahydrofuran-3-carboxylic acid (Formula Removed)8-(4-Octylphenyl)-7-oxa-l,3-diazaspiro[4.4]nonane-2,4-dione (0.5 g, 1.452 mmol) and sodium hydroxide (10.89 ml, 21.77 mmol) were combined in water (8.54 ml) and equipped with a reflux condensor. The mixture was heated at about 100 °C for about 72 h. The reaction was cooled and acidified with concentrated HC1 until pH = 4-5. The product was collected by vacuum filtration and dried under vacuum. The residue was purified by flash column chromatography (1" x 6" of silica) eluting with 1:1 EtOAc/(6:3:l CHCl3/MeOH/NHUOH). The product fractions were combined. The solvents were removed under reduced pressure and the residue triturated with ether. The resulting solid was collected by vacuum filtration and washed with ether to provide 3-amino-5-(4-octylphenyl)tetrahydrofuran-3-carboxylic acid (0.280 g, 0.877 mmol, 60.4 % yield) as a white solid: LC/MS (method A) R, = 3.22 min.; MS m/z: 320.25 (M+H)+. Preparation of (3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol (Formula Removed)3-Amino-5-(4-octylphenyl)tetrahydrofuran-3-carboxylic acid (0.246 g, 0.770 mmol) was dissolved in THF (15.40 ml). A solution of lithium aluminum hydride (0.770 ml, 1.540 mmol) (Aldrich) was added carefully and the reaction stirred for about 3 h. The reaction was quenched by addition of water (60 uL) and stirred for about 30 min. 10% NaOH (180 uL) was added and the reaction stirred for about 1 h. Finally, water (60 uL) was added and the reaction stirred overnight. The mixuture was filtered through Celite® and the solvents removed under reduced pressure. The residue was purified by flash column chromatography (0.5" x 7" of silica) eluting with 10% MeOH in methylene chloride and the product fractions combined. The solvents were removed under reduced pressure to provide (3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol (0.1 g, 0.327 mmol, 42.5 % yield) as a colorless oil: LC/MS (method A) R, = 3.12 min.; MS m/z: 306.42 (M+HT. Preparation of (3-amino-5-methyl-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol (Formula Removed)A solution of lithium aluminum hydride (2.70 ml, 5.40 mmol) (Aldrich) was added carefully to THF (17.99 ml) under nitrogen. 3-amino-5-methyl-5-(4-octylphenyl)tetrahydrofuran-3-carboxylic acid (0.6 g, 1.799 mmol) was added in small portions causing vigorous bubbling. The reaction stirred for about 2 h. TLC in 10% MeOH in methylene chloride showed (Hannessian's stain visualization) reaction complete. The reaction was quenched by addition of water (200 uL) and the reaction 'stirred about 30 min. 10% NaOH (0.6 mL) was added and the reaction stirred about 30 min. Finally, water (200 uL) was added and the reaction stirred about 30 min. The resulting solid was collected by vacuum filtration and washed with ether. The filtrate was concentrated to a colorless oil. The residue was purified by flash column chromatography (40 g Redi-Sep) eluting with 10-20% methanol in methylene chloride and the product fractions combined. Solvents were removed under reduced pressure. The residue was redissolve in methylene chloride and filtered through a syringe filter into a vial and washed through with methylene chloride. Solvent was removed under reduced pressure to provide (3-amino-5-methyl-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol (0.192 g, 0.601 mmol, 33.4 % yield) as a colorless oil that solidified on standing to a white solid: LCMS (method f) R, = 2.21 min.; MS m/z: 320.50 (M+H)+. Scheme for preparation of phosphonates described below: (Formula Removed)Preparation of tert-butyl (lR,3S)-l-(hydroxymethyl)-3-(4-octylphenyl)cyclopentylcarbamate (Formula Removed) ((1R,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)methanol (4.72 g, 15.55 mmol) and pyridine (1.384 ml, 17.11 mmol) (Aldrich) were combined in THF (15.55 ml) under nitrogen to give a colorless solution. Di-tert-butyl dicarbonate (3.93 ml, 17.11 mmol) (Fluka) was added and the reaction stirred for about 4h and a precipitate formed. TLC in 1:1 EtOAc/heptane showed (KMnO4 visualization) reaction complete. Ethyl acetate (150 mL) and water (50 mL) were added and the layers separated and extracted with ethyl acetate (2 x 25 mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered, and evaporated to an off-white solid. The residue was purified by flash column chromatography (120 g Redi-Sep) eluting with ethyl acetate/heptane and the product fractions combined. The solvent was removed under reduced pressure to provide tert-butyl (lR,3S)-l-(hydroxymethyl)-3-(4-octylphenyl)cyclopentylcarbamate (4.086 g, 10.12 mmol, 65.1 % yield) as a white solid: LC/MS (method f) R, = 3.44 min.; MS m/z: 404.35 (M+H)*. Preparation of tert-butyl (1R,3S)-l-formyl-3-(4-octylphenyl)cyclopentylcarbarnate (Formula Removed)Tert-butyl (lR,3S)-l-(hydroxymethyl)-3-(4-octylphenyl)cyclopenty!carbamate (3.9 g, 9.66 mmol) was dissolved in dichloromethane (193 ml) under nitrogen to give a colorless solution. Dess-Martin periodinane (4.51 g, 10.63 mmol) (Aldrich) was added and the reaction stirred for about 3 h. LC/MS showed the reaction was complete. Methylene chloride (100 mL) and water (100 mL) were added and the layers separated and extracted with methylene chloride (2 x SO mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered, and evaporated to an off-white solid. The residue was purified by flash column chromatography (120 g Redi-Sep) eluting with ethyl acetate/heptane and the product fractions combined. Solvents were removed under reduced pressure to provide tert-butyl (lR,3S)-l-formyl-3-(4-octylphenyI)cyclopentylcarbamate (3.40 g, 88%) as an off white solid: LC/MS (method f) R, = 3.58 min.; MS m/z: 401.36 (M+H)+. Preparation of tert-butyl (lR,3S)-l-((E)-2-(diethoxyphosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (Formula Removed)Sodium hydride (0.020 g, 0.498 mmol) (Aldrich) was stirred in THF (3.32 ml) under nitrogen to give a colorless suspension. Tetraethyl methylenediphosphonate (0.124 ml, 0.498 mmol) (ALDRICH) was added and the reaction stirred for about 30 min. Tert-butyl (lR,3S)-l-formyl-3-(4-octylphenyl)cyclopentylcarbamate (0.2 g, 0.498 mmol) was added in small portions and the reaction stirred for about 16 h. Solvents were removed under reduced pressure. Ethyl acetate (50 mL) and water (10 mL) were added and the layers separated and extracted with ethyl acetate (2 x 10 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a yellow oil. The residue was purified by flash column chromatography (40 g Redi-Sep) eluting with ethyl acetate/heptane and the product fractions combined. The sovlent was removed under reduced pressure to provide tert-butyl (lR,3S)-l-((E)-2-(diethoxyphosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.237 g, 0.442 mmol, 89 % yield) as an orange oil: LC/MS (method f) R, = 3.12 min.; MS m/z: 553.42 (M+H2O)+. Preparation of tert-butyl (lR,3S)-l-(2-(diethoxyphosphoryl)ethyl)-3-(4-octylphenyl)cyclopentylcarbamate (Formula Removed)Tert-butyl (lR,3S)-l-((E)-2-(diethoxyphosphoryI)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.237 g, 0.442 mmol) was dissolved in ethanol. Palladium on carbon (0.094 g, 0.088 mmol) was added and the reaction was flushed with hydrogen and hydrogenated at atmospheric pressure for about 72 h. The solution was filtered through a syringe filter and washed through with methanol. Solvent was removed under reduced pressure to provide tert-butyl (lR,3S)-l-(2-(diethoxyphosphoryl)ethyl)-3-(4-octylphenyl)cyclopentylcarbarnate (0.236 g, 0.439 mmol, 99 % yield) as a colorless oil: LC/MS (method f) R, = 3.60 min.; MS m/z: 538.53 (M+H)*. Preparation of 2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)ethylphospbonic.acid (Formula Removed)Tert-butyl (!R,3S)-l-(2-(diethoxyphosphoryl)ethyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.236 g, 0.439 mmol) was dissolved in dichloromethane (4.39 ml) under nitrogen to give a colorless solution. Bromotrimethylsilane (0.569 ml, 4.39 mmol) (Aldrich) was added and the reaction stirred for about 4h. Solvents were removed under reduced pressure. Methanol (4 mL) and water (0.2 mL) were added and the solution was stirred for about 16 h. Solvents were removed under reduced pressure to give a brown oil/solid. Water was added and the solution sonicated while scraping the sides of the vial. The solution was stirred with a stir bar for about 1 h. The resulting solid was collected by vacuum filtration and washed with water and then pentane to provide 2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)ethylphosphonic acid (0.150 g, 0.393 mmol, 90% yield) as a off-white solid on drying under vacuum at 60 °C: LC/MS (method a) R, = 3.15 min.; MS m/z: 382.27 (M+H)+. Preparation of (E)-2-((lRr3S)-l-amino-3-(4-octylphenyl)cyclopentyl)vinylphosphonic acid (Formula Removed)Tert-butyl(lR,3S)-H(E)-2-(diethoxyphosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbainate (0.2 g, 0.373 mmol) (10035787-0263) was dissolved in dichloromethane (3.73 ml) in a sealed vial to give a colorless solution. Bromotrimethylsilane (0.484 ml, 3.73 mmol) (Fluka) was added and the reaction stirred for about 16 h. Solvents were removed under reduced pressure to a thick oil. Methanol (4 mL) and water (0.2 mL) were added. The solution was sonicated and stirred, resulting in a cloudy reaction where a heavy precipitate forms. The solutionw as stirred for about 4 h. Add water (5 mL) and more product precipitated. The resulting solid was collected by vacuum filtration,washed with water and then pentane and dried under vacuum to provide (E)-2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)vinylphosphonic acid (0.117 g, 0.308 mmol, 83 % yield) as a white solid: LCMS (method a) R, = 3.01 min.; MS m/z: 380.21 (M+H)+. Preparation of diethyl 2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)ethylphosphonate (Formula Removed)Tert-butyl (!R,3S)-l-(2-(diethoxyphosphoryI)ethyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.2 g, 0.372 mmol) was dissolved in dichloromethane (1.860 ml) in a sealed vial to give a colorless solution. TFA (1.860 ml) was added and the reaction stirred for about 1 h. Solvents were removed under reduced pressure. Methylene chloride (25 mL) and saturated sodium bicarbonate (25 mL) were added and the layers separated and extracted with methylene chloride (2 x 10 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a yellow oil. The oil was dissolve in ether (15 mL). 1 M HC1 in dioxane (3 mL) was added. Solvents were removed under reduced pressure. The solid was redissolved in water and lyophilized. The resulting white/tan solid was suspended in ether and the resulting solid was collected by vacuum filtration and washed with ether then heptane to provide diethyl 2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)ethylphosphonate (0.0787 g, 0.180 mmol, 48.4 % yield) as a white solid on drying under vacuum: LCMS (method a) R, = 3.46 min.; MS m/z: 438.48 (M+H)+. Preparation of tert-butyl 2-(4-(4-bromophenyl)-lH-l,2,3-triazol-l-yl)acetate (Formula Removed)A 5 mL microwave reaction vial equipped with a pressure releasing septa cap was charged with tert-butyl 2-bromoacetate (0.408 ml, 2.76 mmol) and sodium azide (0.215 g, 3.31 mmol) in Water (0.552 ml) and DMSO (4.97 ml) at it. The resulting suspension was heated at 65 °C for 15 h. The reaction was allowed to cool to it and ice was added in one portion. The resulting solid was removed by filtration to give tert-butyl 2-(4-(4-bromophenyl)-lH-l,2,3-triazol-l-yl)acetate (0.868g, 2.57 mmol, 93% yield): LCMS (method c) R, = 2.35 min.; MS m/z: 338,340 (M+H)+. Preparation of tert-butyl 2-(4-(4-(oct-l-ynyl)phenyl)-lH-l,2,3-triazol-l-yl)acetate (Formula Removed)A 25 mL round-bottomed flask equipped with a reflux condenser outfitted with anitrogen inlet adapter was charged with tert-butyl 2-(4-(4-bromophenyl)-lH-l,2,3-triazol-l-yl)acetate (0.200 mg, 0.591 mmol), bis-acetonitrilepalladium(II) chloride (0.003 g, 0.012 mmol), dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.017 g, 0.035 mmol), and cesium carbonate (0.674 g, 2.07 mmol). The flask was evacuated and filled with nitrogen and then acetonitrile (12 mL) and 1-octyne (0.228 g, 2.07 mmol) were each added dropwise via syringe. The resulting mixture was heated at 100 °C for 72 h. The reaction was allowed to cool to rt and filtered through a pad of celite. The filtrate was concentrated and purified by silica gel chromatography (elution with ethyl acetate in heptane) to provide tert-butyl 2-(4-(4-(oct-l-ynyl)phenyl)-lH-l,2,3-triazol-l-yl)acetate (0.115 g, 0.304 mmol, 51% yield) as a solid: LCMS (method a) R, = 3.89 min.; MS m/z: 368 (M+H)+. Preparation of tert-butyl 2-(4-(4-octylphenyI)-lH-l,2,3-triazol-l-yl)acetate (Formula Removed)A 50 mL round-bottomed flask equipped with a rubber septum outfitted with a hydrogen-filled balloon was charged with tert-butyl 2-(4-(4-(oct-l-ynyl)phenyl)-lH-l,2,3-triazol-l-yl)acetate (0.083 g, 0.226 mmol), Pd(OH)2 (3.17 mg, 0.023 mmol), and ammonium carbonate (0.217 g, 2.259 mmol) in ethanol (4.5 ml) at rt. The reaction mixture was allowed to stir at rt for 6 h. The resulting mixture was filtered through a pad of celite with the aid of EtOAc. The filtrate was concentrated to afford tert-butyl 2-(4-(4-octyIphenyl)-lH-l,2,3-triazol-l-yl)acetate (0.070 g, 0.175 mmol, 78% yield) as a solid: LCMS (method a) R, = 4.20 min.; MS m/z: 372(M+H)+. Preparation of 2-(4-(4-octylphenyl)-lH-l,2,3-triazol-l-yl)acetic acid (Formula Removed)A 50 mL round-bottomed flask equipped with a nitrogen inlet adapter was charged with tert-butyl 2-(4-(4-octylphenyl)-lH-l,2,3-triazol-l-yl)acetate (0.042 g, 0.113 nunol) and TFA (0.044 ml, 0.565 mmol) in CH2Cl2 (2.261 ml) at rt. The reaction mixture was allowed to stir at rt for 20 h. An additional portion of TFA (0.50 ml, 6.49 mmol) was added and the resulting mixture was allowed to stir at it for an additional 24h. The mixture was concentrated to provide a solid that was purified by reverse-phase HPLC (elution with MeCN in water) to give 2-(4-(4-octylphenyl)-lH-l,2,3-triazol-l-yl)acetic acid (0.025 g, 0.079 mmol, 70% yield) as a solid: LCMS (method a) R, = 3.41 min.; MS m/z: 316(M+H)+. Preparation of (5R,7R)-7-(3-iodo-4-methoxyphenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (Formula Removed)A 50 mL round-bottomed flask equipped with rubber septum and nitrogen inlet needle was charged with (5R,7R)-7-(4-methoxyphenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.504 g, 2.038 mmol) in Acetonitrile (10.2 mL) to give a colorless solution. The flask was protected from light with foil. IC1 (0.255 ml, 5.10 mmol) was added dropwise via syringe. The resulting solution was allowed to stir at rt for 2 h. Sat'd Na2S2O3 solution was added in one portion and the mixture was allowed to stir at rt overnight. The reaction mixture was diluted with EtOAc. The organic phase was separated and washed with sat NaHCO3 and sat NaCl. The organic phase was dried over MgSO4, filtered, and concentrated to give (5R,7R)-7-(3-iodo-4-methoxyphenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.760 g, 2.04 mmol, 100% yield) as a solid: LCMS (method a) R, = 3.21 min.; MS m/z: 374 (M+H)+. Preparation of (5R,7R)-7-(4-hydroxy-3-iodophenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (Formula Removed)A 25 mL round-bottomed flask equipped with a rubber septum and nitrogen inlet needle was charged with (5R,7R)-7-(3-iodo-4-methoxyphenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.209 g, 0.560 mmol) in dichloromethane (5.6 ml) to give a colorless solution. BBr3 solution in DCM (1.57 ml, 1.57 mmol) was added dropwise via syringe at 0 °C. The resulting solution was allowed to stir at 0 °C for 1 h. The sample was treated with MeOH at 0 °C and concentrated. The residue was treated with three additional 20-mL portions of MeOH and concentrated after each addition to afford (5R,7R)-7-(4-hydroxy-3-iodophenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.198 g, 0.551 mmol, 98% yield) as an oily-solid: LCMS (method c) R, = 1.77 min.; MS m/z: 358 (M-H)~. Preparation of (5R,7R)-7-(2-phenylbenzofuran-5-yl)-3-oxa-l-azaspiro[4.4]nonan-2-one (Formula Removed)A 100 mL round-bottomed flask equipped with rubber septum and nitrogen inlet needle was charged with (5R,7R)-7-(4-hydroxy-3-iodophenyl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.198 g, 0.551 mmol), bis(triphenylphosphine)pal]adium(II) chloride (0.039 g, 0.055 mmol), and copper(I) iodide (0.010 g, 0.055 mmol), evacuated and filled with nitrogen, and then Et3N (3.84 mL) was added to give a suspension. Ethynylbenzene (0.073 ml, 0.662 mmol) was added dropwise via syringe and the resulting suspension was allowed to stir at rt for 6 h. The suspension was filtered through a pad of celite and concentrated. The residue was triturated with water and washed with three 30-mL portions of water. The resulting solid was air-dried to give a solid that was purified via silica gel chromatography (gradient elution with 50%-100% ethyl acetate in heptane) to afford (5R,7R)-7-(2-phenylbenzofuran-5-yl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.055 g, 0.165 mmol, 30% yield) as a solid: LCMS (method a) R, = 3.86 min.; MS m/z: 351 (M+NIt»)+. Preparation of ((lRr3R)-l-amino-3-(2-phenyIbenzofuran-5-yl)cyclopentyl)methanol (Formula Removed)A 100 mL round-bottomed flask equipped with reflux condensor outfitted with a nitrogen inlet adapter was charged with (5R,7R)-7-(2-phenylbenzofuran-5-yl)-3-oxa-l-azaspiro[4.4]nonan-2-one (0.055 g, 0.165 mmol) in dioxane (2.6 ml). Lithium hydroxide (0.079 g, 3.30 mmol) was added in one portion as a solution in water (0.660 ml). The reaction mixture was heated at 100 °C for 16 h and then approximately ImL of 4N HC1 solution in dioxane was added. The solution was concentrated and the resulting solid was triturated with 2 mL of water and 2 mL of EtOAc. The material was filtered through a sintered glass funnel, washed with EtOAc, and dried open to the air to give a powder that was suspended in acetic acid and agitated for 5 min. The resulting suspension was filtered through a sintered glass funnel and the filtrate was concentrated to afford ((1R,3R)-1-amino-3-(2-phenylbenzofuran-5-yl)cyclopentyl)methanol (0.003 g, 0.009 mmol, 5% yield) as a solid: LCMS (method a) R,= 2.73 min.; MS m/z: 308 (M+H)+. Preparation of diethyl (ethoxy(methyl)phosphoryl)methylphosphonate (Formula Removed)Reference: J. Organomet. Chem. 2002, 662, 83-97. THF (30.0 ml) was cooled to about -78 °C in a dry ice/acetone bath under nitrogen. A solution of sec-butyllithium (9.39 ml, 13.15 mmol) was added in one portion. A solution of diethyl methylphosphonate (1.923 ml, 13.15 mmol) dissolved in THF (15 mL) was added dropwise and the reaction stirred for about 1 h. A solution of methylphosphonic dichloride (0.534 ml, 5.90 mmol) dissolved in THF (15 mL) was added and the reaction stirred for about 2 h. Ethanol (0.345 ml, 5.90 mmol) was added and the reaction stirred for about 16 h. Methylene chloride (50 mL) and water (30 mL) were added and the layers separated. The aqueous layer was extracted with methylene chloride (2 x 20 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a colorless oil. The residue was purified by flash column chromatography (80 g Redi-Sep) eluting with EtOAc. The solvent was switched to 10% methanol/methylene chloride and the product eluted. The solvents were removed under reduced pressure to provide diethyl (ethoxy(methyl)phosphoryl)methylphosphonate (0.676 g, 2.62 mmol, 19.92% yield) as a colorless oil: 'H NMR (400 MHz, CDC13) 6 (ppm) 4.25-4.05 (m, 6H), 2.41 (dd, 2H), 1.70 (d, 3 H), 1.35 (t, 9H). Preparation of (lR3S)-l-((E)-2-(ethoxy(methyl)phosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (Formula Removed)Reference: Tel. Lett. 1993,34, 1585-1588. Magnesium bromide diethyl etherate (0.120 g, 0.465 mmol) and diethyl (ethoxy(methyl)phosphoryl)methylphosphonate (0.1 g, 0.387 mmol) were combined in THF (1.174 ml) in a sealed vial to give a white suspension. The mixture was stiired for about 15 min. Triethylamine (0.060 ml, 0.434 mmol) was added and the reaction stirred for about 30 min. Tert-butyl (lR,3S)-l-formyl-3-(4-octylphenyl)cyclopentylcarbamate (0.184 g, 0.457 mmol) was added and the reaction stirred for about 72 h. The reaction was quenched by addition of 0.1 N HCI (2 mL). Methylene chloride (15 mL) was added and the layers separated. The aqueous layer was extracted with methylene chloride (2 x 10 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a colorless oil. The residue was purified by flash column chromatography (12 g Redi-Sep) eluting with EtOAc and the product fractions combined. The solvents were removed under reduced pressure to provide tert-butyl (1R,3S)-1-((E)-2-(ethoxy(methyl)phosphoryl)vinyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.037 g, 0.073 mmol, 18.89% yield) as a colorless oil: LCMS (method f) R, = 2.92 min.; MS m/z: 506.42 (M+H)*, 'H NMR (400 MHz, CDC13) 5 (ppm) 7.12 (m, 4H), 6.86 (t, 1H), 5.77 (t,lH), 4.80 (s, 1H), 4.10-3.90 (m, 2H), 3.22 (m, 1H), 2.58 (t, 2H), 2.52-2.42 (m, 1H), 1.60 (m, 3H), 1.53 (d, 3H), 1.43 (s, 9H), 1.36-1.24 (m, 14H), 0.89 (t, 3H). Preparation of (lRr3S)-l-(2-(ethoxy(methyl)phosphoryl)ethyI)-3-(4-octylphenyl)cyclopentylcarbamate (Formula Removed)Tert-butyl (1R,3S)-1 -((E)-2-(ethoxy(methyl)phosphoryl)vinyi)-3-(4- octylphenyl)cyclopentylcarbamate (0.037 g, 0.073 mmol) was dissolved in ethanol (1.463 ml). Palladium on carbon (7.79 mg, 7.32 umol) was added, the reaction was flushed with hydrogen, and hydrogenated at atmospheric pressure for about 16 h. The mixture was filtered through a syringe filter and wash through with methanol. The solvents were removed under reduced pressure to provide tert-butyl (lR,3S)-l-(2-(ethoxy(methyl)phosphoryl)ethyl)-3-(4- octylphenyl)cyclopentylcarbamate (0.047 g, 0.093 mmol, 127 % yield) as a colorless oil: LCMS (method f) R, = 2.62 min.; MS m/z: 508.38 (M+H)+, !H NMR (400 MHz, CDCI3) 6 (ppm) 7.12 (dd, 4H), 4.60 (s, 1H), 4.09 (m, 2H), 3.12 (m, 1H), 2.57 (t, 2H), 2.30 (m, 1H), 2.20-1.55 (m, 13H), 1.48 (d, 3H), 1.45 (s, 9H), 1.35-1.26 (m, 14H), 0.89 (t, 3H). Preparation of 2-((lR^S)-l-amino-3-(4-octylphenyl)cycIopentyl)ethyl(methyl)phosphinic acid, Acetic Acid (Formula Removed)Reference: J. Med. Chem. 1995,38, 3313-3331. Tert-butyl (lR,3S)-l-(2-(ethoxy(methyl)phosphoryl)ethyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.047 g, 0.093 mmol) was dissolved in dichloromethane (0.926 ml) in a sealed vial to give a colorless solution. Bromotrimethylsilane (0.060 ml, 0.463 mmol) was added and the reaction stirred for about 16 h. The solvents were removed under reduced pressure. Water (1 mL) and methanol (5 mL) were added and the reaction stirred for about 4 h. The solvents were removed under reduced pressure. Water (5 mL) was added and the pH adjusted with ammonium hydroxide to about pH = 5. The mixture formed a clear gel. The mixture was frozen and lyophilized. Add water to dissolve product. Semi-prep HPLC in 1 mM ammonium acetate buffer. Product fractions were lyophilized to a sticky white solid that was dried under vacuum at 60 °C. Redissolve in methanol and transfer to vial. The solvents were removed under reduced pressure and dried under vacuum at 35 °C to give 2-((lR,3S)-l-amino-3-(4-octylphenyl)cyclopentyl)ethyl(methyl)phosphinic acid, acetic acid salt (0.029 g, 0.066 mmol, 71.3 % yield) as a colorless glassy solid: LCMS (method g) R, = 1.80 min.; MS m/z: 508.38 (M+H)+, 'H NMR (400 MHz, CDC13) 5 (ppm) 7.15 (dd, 4H), 3.03 (m, 1H), 2.54 (t, 2H), 2.38-2.02 (m, 8H), 1.88-1.78 (m, 3H), 1.60-1.53 (m, 2H), 1.38-1.22 (m, 14H), 0.89 (t, 3H). Preparation of ethyl l-(tert-butoxycarbonylamino)-3-(4-octylphenoxy)cyclopentanecarboxylate (Formula Removed)4-octylphenol (1.019 g, 4.94 mmol), ethyl l-(tert-butoxycarbonylamino)-3-hydroxycyclopentanecarboxylate (0.9 g, 3.29 mmol) (Pharmacore), and triphenylphosphine (2.74 g, 8.23 mmol) (Argonaut) were combined in THF (32.9 ml) under nitrogen. Molecular sieves 4A (3.29 mmol) were added and the reaction stirred about 30 m in. Di-tert-butyl azodicarboxylate (1.137 g, 4.94 mmol) was added and the reaction stirred for about 18 h. The reaction was filtered through celite and washed through with methylene chloride. The solvents were removed under reduced pressure to provide an oil. The residue was chromatographed on a 40 g redi sep column with gradient EtOAc/heptane (10-50%). Remove solvent under reduced pressure to provide ethyl 1-(tert-butoxycarbonylamino)-3-(4-octylphenoxy)cyclopentanecarboxylate (1.175 g, 2.55 mmol, 77 % yield) as a colorless oil: LCMS (method f) R, = 3.58 min.; MS m/z: 462.44 (M+H)+, 'HNMR (400 MHz, CDC13) 8 (ppm) 7.13 (m, 2H), 6.77 (m, 2H), 5.20^.82 (2 broad s, cis/trans isomers, 1 H), 4.20 (q, 1H), 2.72-1.98 (m, 3H), 2.52 (t, 2H), 1.58 (m, 2H), 1.45 (m, 5H), 1.33-1.20 (m, 12H), 0.89 (t, 3H). Preparation of ethyl l-amino-3-(4-octyIphenoxy)cyclopentanecarboxylate (Formula Removed)Ethyl l-(tert-butoxycarbonylamino)-3-(4-octylphenoxy)cyclopentanecarboxylate (1.1 g, 2.383 mmol) was dissolved in dichloromethane (11.91 ml) under nitrogen. Trifluoroacetic acid (11.91 ml, 155 mmol) was added and the reaction stirred for about 2 h. Solvents were removed under reduced pressure. Add 1 N NaOH and extract with ethyl acetate (2x). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to a colorless oil. Chromatograph on a 40 g redi-sep column in 20-50% EtOAc in heptane. Remove solvent under reduced pressure to provide ethyl l-amino-3-(4-octylphenoxy)cyclopentanecarboxylate (0.554 g, 1.532 mmol, 64.3 % yield) as a colorless oil: LCMS (method f) R, = 2.91, 3.15 min.; MS m/z: 363.56, 363.49 (M+H)+, 'H NMR (400 MHz, CDCI3) 6 (ppm) 7.10 (m, 2H), 6.82 (m, 2H), 5.00-4.85 (2 m, cis/trans isomers, 1H), 4.26-4.18 (m, 2H), 2.65-2.54 (m, 3H), 2.45-1.92 (m, 7H), 1.72-1.56 (m,2H), 1.37-1.24 (m, 14H),0.91(t,3H). Preparation of (l-amino-3-(4-octylphenoxy)cyclopentyl)methanoI (A-1007664.0) (Formula Removed)Ethyl l-amino-3-(4-octylphenoxy)cyclopentanecarboxylate (0.554 g, 1.532 mmol) was dissolved in THF (15.32 ml) open to the air. A solution of lithium aluminum hydride (1.532 ml, 3.06 mmol) was added carefully and the reaction stirred for about 2 h. The reaction was quenched with water (0.116 mL) and stirred for about 30 min. 1 N NaOH (0.350 mL) was added and the reaction stirred for about 30 min. An additional amount of water (0.116 mL) was added and the reaction stirred for more than 30 min. The resulting precipitate was removed by syringe filter. The solution was concentrated on the rotovap and then chromatographed over silica gel in 4:1 EtOAc/(6:3:1 CHCla/MeOH/NHtOH). Remove solvent under reduced pressure to provide (l-amino-3-(4-octylphenoxy)cyclopentyl)methanol (0.335 g, 1.049 mmol, 68.4 % yield) as a colorless oil: LCMS (methoda)R, = 3.12min.;MSm/z: 321.17 (M+H)+, !H NMR (400 MHz, CDC13) 6 (ppm) 7.06 (m, 2H), 6.76 (m, 2H), 4.90-4.75 (2 m, cis/trans isomers, 1H), 3.56-3.36 (2 m, cis/trans isomers, 2H), 2.52 (t, 2H), 2.25-1.66 (m, 9H), 1.61-1.50 (m, 2H), 1.35-1.22 (m, 11H), 0.89 (t, 3H). Preparation of (l-amino-3-(4-octylphenoxy)cyclopentyl)methyl dihydrogen phosphate (Formula Removed) (l-Amino-3-(4-octylphenoxy)cyclopentyl)methanol (0.052 g, 0.163 mmol) was dissolved in THF (3.26 ml) in a sealed vial. A solution of lithium bis(trimethylsilyl)amide (0.163 ml, 0.163 mmol) was added carefully and the reaction stirred for about 15 min. Tetrabenzyl diphosphate (0.088 g, 0.163 mmol) was added and the reaction stirred for about 20 h. The heavy white precipitate was removed by vacuum filtration and washed with THF. The filtrate was concentrated and dissolved in acetic acid. Palladium on carbon (0.017 g, 0.016 mmol) was added and the reaction flushed with hydrogen. Hydrogenate at atmospheric pressure overnight. Filter and concentrate to remove acetic acid. Add water and sonicate. The resulting solid was collected by vacuum filtration and washed with water to provide (l-amino-3-(4-octylphenoxy)cyclopentyl)methyl dihydrogen phosphate (0.032 g, 0.080 mmol, 49.2 % yield) as a tan solid on drying under vacuum at 60 °C: LCMS (method a) R, = 3.10 min.; MS m/z: 400.24 (M+H)+, 'H NMR (400 MHz, CDC13) 6 (ppm) 7.2 (d, 2H), 6.83 (d, 2H), 4.98-4.75 (2 m, cis/trans isomers, 1H), 3.85 (m, 1 H), 2.40-1.6 (m, 5H), 1.55 (m, 2H), 1.24 (m, 12H), 0.91 (t, 3H). What is claimed: 1. A compound of Formula I (Formula Removed) wherein DisH,N(R5)2orOR6; XisCH,C(CH3)orN; Y is CH2,0, S or MR3; wherein R3 is hydrogen, or straight or branched (C1-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2),-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C20)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (Cr C20) alkyl, (C1-C20) alkoxy, (C1-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted (C1-C20)alkyl, heteroaryl substituted (C2-C20)alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R1 and R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; nisi, 2 or 3; t is 1,2 or 3; and u is 0,1 or 2; provided that A and D are not both Hat the same time.; and provided the compound is not (Formula Removed)wherein X is CH or N; Y is CH2, NH, N(CH3), S or O. 2. The compound of claim 1 wherein A is H, -C(O)-OCH3, -C(O)-NR6, CN, C(O)-NHCH3, COOR6, -R4-COOH, or optionally substituted azetidinyl, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20)) alkenylene, straight or branched (C1-C20) alkynylene; R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C10) alkyl, (C1-C10) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C1-C10) cycloalkyl substituted alkoxy, (C2-C10) alkenyl, aryl substituted (C2-C10) alkenyl, (C2-C10) alkynyl, aryl substituted (C2-CIO) alkynyl, aryl, aryl substituted (C1-C10) alkyl, heteroaryl substituted (C1-C10) alkyl, aryl substituted (C1-C10) alkoxy, heteroaryl substituted (C1-C10) alkoxy, (C1-C10) alkyl substituted aryl, arylalkyl and aryl substituted arylalkyl; wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, halo, hydroxy, (Ci-Cio) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or MR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R1 and R2 are optionally substituted with oxo or halo. 3. The compound according to claim 2 wherein the compound is a formula of Formula la: (Formula Removed)and isomers, stereoisomers, esters, prodrugs, and pharmaceutically-acceptable salts thereof, wherein; X is CH; Y is CH2 or O; A is -C(O)-OCH3, -COOH, -R4-COOH, -C(O)-NHCH3, or optionally substituted azetidinyl; wherein R4 is straight or branched (C1-C10) alkylene, straight or branched (C1-C10) alkenylene, or straight or branched (C1-C10) alkynylene; R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C10) alkyl, (C1-C10) alkoxy, (C3-C10) cycloalkyl substituted alkyl, (C3-C10) cycloalkyl substituted alkoxy, (C2-C10) alkenyl, aryl substituted (C2-C10) alkenyl, (C2-C10) alkynyl, aryl substituted (C2-C10) alkynyl, aryl, aryl substituted (C1-C10)alkyl, heteroaryl substituted (C1-C10)alkyl, aryl substituted (C1-C10)alkoxy, heteroaryl substituted (C1-C10)alkoxy, (C1-C10)alkyl substituted aryl, arylalkyl and aryl substituted arylalkyl; , wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, CF3, halo, hydroxy, (C1-C10) alkoxy, or CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; and n is 1 or 2. 4. The compound according to claim 3 wherein Y is CH2; A is -CH2-COOH, COOH or(Formula Removed) R1 and R2 are independently selected from the group consisting of hydrogen, (CrCi0) alkyl, (C2-C10) alkenyl, (C2-C10) alkynyl and aryl substituted (C1-C10) alkyl; wherein such R1 and R2 groups may be optionally substituted with (C1-C10) alkyl, halo, hydroxy, (C1-C10) alkoxy, or cyano; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen. 5. The compound according to Claim 4 wherein X is CH; Y is CH2; A is COOH; R1 is (C1-C10)alkyl, (C2-C]0)alkenyl or (C2-C10)alkynyl; R2 is H; and mis 1. 6. The compound according to Claim 5 wherein the compound is (Formula Removed) 7. The compound according to Claim 1 wherein Y is CH2, O, S or NR3; wherein R3 is hydrogen, or (C1-C10) alkyl; A is H, -CH2OH, -CH2OH,-C(O)-OCH3, -optionally substituted -(CH2)n-P(=0)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), -CH=CH-O-P(=O)(OR7)(OR7) or CN; R1 and R2 are independently selected from the group consisting of hydrogen, halo, straight or branched (C1-C10) alkyl, (C1-C10) alkoxy, (C3-C10) cycloalkyl substituted alkyl, (C3-C10) cycloalkyl substituted alkoxy, (C2-C10) alkenyl, aryl substituted (C2-C10) alkenyl, (C2-C10) alkynyl, ary! substituted (C2-C10) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted (C2-C10)alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, (C2-C10)alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, cyano and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from straight or branched (C2-C10) alkyl, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C10) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; R6 is independently selected from H or optionally substituted (C1-C2)alkyl; R7 is independently selected from H or optionally substituted (C1-C2)alkyl; and u is 1 or 2. 8. The compound according to Claim 1 wherein the compound is a compound of Formula Ib: (Formula Removed)wherein; XisCHorN; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or (C1-C20) alkyl; A is -CH2-OH, optionally substituted -CH2-P(=(O)(OR7)(OR7) or optionally substituted - CH2-O-P(=(O)(OR7)(OR7); R1 and R2 are independently selected from the group consisting of hydrogen, halo, (C1-C20) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalky] and aryl substituted arylalkyl; wherein such R2 groups may be optionally substituted with (C1-C20) alkyl, halo, hydroxy, (C1-C20) alkoxy, or cyano; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo. 9. The compound of claim 7 wherein X is CH; Y is CH2; A is -CH2OH, optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7) or optionally substituted -{CH2)n-P(=O)(OR7)(OR7). R1 and R2 are independently selected from the group consisting of hydrogen, halo, straight or branched (C1-C10) alkyl, aryl substituted (C1-C10) alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, (C1-C10)alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C10) alkyl, halo and (C1-C10) alkoxy; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyi, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R6 is independently selected from H or optionally substituted (C1-C2)alkyl; and u is 1 or 2. 10. The compound of claim 9 wherein A is -CH2OH or optionally substituted -(CH2)0-O-P(=O)(OR7)(OR7); D is NH2; R1 and R2 are independently selected from the group consisting of hydrogen, optionally substituted (C1-C10) alkyl; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen; wherein one of R1 and R2 is other than hydrogen;; m is 1; and 11. The compound of claim 10 wherein the compound is (Formula Removed) 12. A compound of the formula (Formula Removed)13. A pharmaceutical composition comprising a compound of Formula I Wherein(Formula Removed)DisH,N(R5)2,orOR6; XisCH,C(CH3)orN; Y is CH2,0, S or MR3; wherein R3 is hydrogen, or straight or branched (Ci-Ci0) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2)t-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C20)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (Q-C20) alkyl, (C1-C20) alkoxy, (C1-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C1-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2- CM) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alky], aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or MR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alky], alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)a]kyl, or -C(O)-O-(C,-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; nis 1,2 or 3; tis 1,2 or 3; and u is 0,1 or 2;or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof and a pharmaceutically acceptable diluent or carrier. 14. A method of treating a disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of Formula I wherein(Formula Removed) DisH,N(R5)2,orOR6; XisCH,C(CH3)orN; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (C1|-C10) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2) -O(CH2),-COOH,-, -C(0)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C,-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (CpC^) alkynylene, (C3-CaOcycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (C1 CM) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C2o) alkenyl, (C1-C20) alkynyl, aryl substituted (C2-CM) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R' and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C,-Ca)) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (CrC2)alkyl or optionally substituted phenyl; m is 1 or 2; nis 1,2 or 3; t is 1,2 or 3; and u is 0, 1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. 15. The method of claim 14 wherein the disorder is rheumatoid arthritis, lupus, Crohn's disease, asthma, diabetes, pain or psoriasis. 16. A method of treating a central nervous system disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of Formula I wherein DisH,N(R5)2,orOR6; X is CH, C(CH3) or N; Y is CH2, O, S or NR3; wherein R3 is hydrogen, or straight or branched (CrCi0) alkyl; A is H, hydroxy, -CH2OH, -CH(OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2)t-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=0)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C2o)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (C,-CM) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-C20) alkynyl, aryl substituted (C2-C20) alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (Ci-CaO alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)alkyl-optionally substituted prienyl; each R6 is independently H or optionally substituted (C1-C2)alkyl; each R7 is independently H, optionally substituted (C1-C2)alkyl or optionally substituted phenyl; m is 1 or 2; nis 1,2 or 3; t is 1,2 or 3; and u is 0, 1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. 17. A method of treating multiple sclerosis comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of claim 1 or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof. 18. A packaged pharmaceutical comprising one or more compounds according to Formula I wherein (Formula Removed)DisH,N(R5)2,orOR6; XisCH,C(CH3)orN; Y is CH2,0, S or NR3; wherein R3 is hydrogen, or straight or branched (Q-Cio) alkyl; A is H, hydroxy, -CH2OH, -CH{OH)CH3, -C(O)-OCH3, -C(OH)(CH3)2, -O(CH2),-COOH,-, -C(O)-NR6, optionally substituted-(CH2)n-P(=O)(OR7)(OR7), optionally substituted -(CH2)n-O-P(=O)(OR7)(OR7), optionally substituted-(CH2)n-P(=O)(OR7)(R7), -CH=CH-P(=O)(OR7)(OR7), C(O)-NHCH3, CN, COOR6 or -R4-COOH, wherein R4 is straight or branched (C1-C20) alkylene, straight or branched (C1-C20) alkenylene, straight or branched (C1-C20) alkynylene, (C3-C2o)cycloalkyl, or optionally substituted azetidinyl; R1 and R2 are independently selected from the group consisting of hydrogen, CF3, halo, (Cr CM) alkyl, (C1-C20) alkoxy, (C3-C20) cycloalkyl substituted alkyl, (C3-C20) cycloalkyl substituted alkoxy, (C2-C20) alkenyl, aryl substituted (C2-C20) alkenyl, (C2-Ca)) alkynyl, aryl substituted (C2-C20 alkynyl, aryl, aryl substituted alkyl, heteroaryl substituted alkyl, aryl substituted alkoxy, heteroaryl substituted alkoxy, alkyl substituted aryl, arylalkyl, aryl substituted arylalkyl, arylalkyl substituted arylalkyl, CN and -O-indolizinyl; wherein such R1 and R2 groups may be optionally substituted with one or more substitutents independently selected from (C1-C20) alkyl, CF3, halo, hydroxy, (C1-C20) alkoxy, OCF3, and CN; wherein one or more of the carbon atoms in the R1 or R2 groups can be independently replaced with non-peroxide oxygen, sulfur or NR8; wherein R8 is hydrogen or (C1-C20) alkyl group; wherein one of R1 and R2 is other than hydrogen; and wherein the alkyl, alkenyl, and alkynyl groups in R2 are optionally substituted with oxo or halo; each R5 is independently H, optionally substituted (C1-C3)alkyl, or -C(O)-O-(C1-C3)aIkyl-optionally substituted phenyl; each R6 is independently H or optionally substituted (C|-C2)alkyl; each R7 is independently H, optionally substituted (Ci-C2)alkyl or optionally substituted phenyl; m is 1 or 2; n is 1, 2 or 3; t is 1,2 or 3; and u is 0,1 or 2; or a pharmaceutically acceptable salt, solvate, hydrate, metabolite, prodrug, enantiomer or stereoisomer thereof and instructions for use. 19. The packaged pharmaceutical according to claim 18 wherein the compound or compounds are present in a therapeutically effective amount. 20. A compound of Formula 2, Formula 3 or Formula 4 (Formula Removed)21. A compound of Formula 5, Formula 6, Formula 7, Formula 8, Formula 9 or Formula 10 (Formula Removed) 21. A compound of Formula 11 or Formula 12 (Formula Removed)