LAVERY KAREN (US)
KREMSKY JONATHAN N (US)
MCKEARIN JAMES M (US)
WO2017160116A9 | 2017-11-30 |
US20120022013A1 | 2012-01-26 | |||
US4361572A | 1982-11-30 | |||
US20170325459A1 | 2017-11-16 | |||
US20180162834A1 | 2018-06-14 | |||
EP3369738A1 | 2018-09-05 | |||
US20180186824A1 | 2018-07-05 | |||
US20170189433A1 | 2017-07-06 | |||
US201962886869P | 2019-08-14 | |||
US201962889376P | 2019-08-20 | |||
EP3431472A2 | 2019-01-23 |
LEE, ANNU. REV. PHARMACOL. TOXICOL., vol. 41, 2001, pages 317 - 345
LIN ET AL., CURR. OPIN. CELL. BIOL., vol. 15, 2003, pages 241 - 246
IMAI ET AL., NATURE, vol. 403, 2000, pages 795 - 800
LANDRY ET AL., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 278, 2000, pages 685 - 690
SMITH ET AL., PROC. NATL. ACAD. SCI. USA, vol. 97, 2000, pages 6658 - 6663
KANG ET AL., MOL. CELLS, vol. 27, 2009, pages 667 - 671
GALLI ET AL., J. MED. CHEM., vol. 56, no. 16, 2013, pages 6279 - 6296
GREENEWUTS: "Protective Groups in Organic Chemistry", 1999, JOHN WILEY & SONS
HARRISON ET AL.: "Compendium of Synthetic Organic Methods", vol. 1-8, 1971, JOHN WILEY & SONS
ROSKAR, R. ET AL., ANALYTICAL METHODS FOR QUANTIFICATION OF DRUG METABOLITES IN BIOLOGICAL SAMPLES, 2012, pages 87 - 91
"Handbook of Pharmaceutical Excipients", 1986
CLAIMS 1. A compound having a structure represented by Formula 1: 1 and/or one or more salts thereof, wherein Ring A is a carbocycle or heterocycle, wherein said carbocycle or heterocycle is aromatic; X is H or a phosphate group; R1 is selected from H, a C1-C6 alkyl group, a substituted or unsubstituted carbocycle when taken together with R2 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R2 wherein said heterocycle may be aromatic or non-aromatic; each R2 is independently selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, and a substituted or unsubstituted heterocycle when taken together with R1 wherein said heterocycle may be aromatic or non-aromatic; each R3 is independently selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, a substituted or unsubstituted carboxamide, a substituted or unsubstituted carbocycle when taken together with R4 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R4 wherein said heterocycle may be aromatic or non-aromatic; and R4 is selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, a substituted or unsubstituted carboxamide, a cyano group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted carbocycle or heterocycle wherein said heterocycle or carbocycle may be aromatic or non-aromatic, a substituted or unsubstituted carbocycle when taken together with R3 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R3 wherein said heterocycle may be aromatic or non-aromatic. 2. A compound having a structure represented by Formula 2: and/or one or more salts thereof, wherein X is H or a phosphate group; R1 is H or a C1-C6 alkyl group; each R2 is independently selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, and a substituted or unsubstituted C1-C6 alkoxy group; each R3 is independently selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, a substituted or unsubstituted carboxamide, a substituted or unsubstituted carbocycle when taken together with R4 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R4 wherein said heterocycle may be aromatic or non-aromatic; and R4 is selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, a substituted or unsubstituted carboxamide, a substituted or unsubstituted carbocycle when taken together with R3 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R3 wherein said heterocycle may be aromatic or non-aromatic. 3. The compound of claim 2, wherein said compound has a structure represented by Formula 2a: 2a and/or one or more salts thereof, wherein R3 is independently selected from H, a substituted or unsubstituted carbocycle when taken together with R4 wherein said carbocycle may be aromatic or non-aromatic, and a substituted or unsubstituted heterocycle when taken together with R4 wherein said heterocycle may be aromatic or non-aromatic; R4 is independently selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, a substituted or unsubstituted carboxamide, a substituted or unsubstituted carbocycle when taken together with R3 wherein said carbocycle may be aromatic or non- aromatic, and a substituted or unsubstituted heterocycle when taken together with R3 wherein said heterocycle may be aromatic or non-aromatic; and further wherein at least one of R3 and R4 is not H. 4. The compound of any one of claims 2 or 3, wherein R3 is H; and R4 is selected from a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, and a substituted or unsubstituted carboxamide. 5. The compound of any one of claims 2-4, wherein X is H; and R4 is a carboxymethyl ester group. 6. The compound of any one of claims 2-5, wherein the compound is selected from Compounds 1-5, 11, 12, 14, 15, 18, 19, 21, 23, 24, 26, 27, 29, 32, and 35: 14 15 7. The compound of claim 2, wherein said compound has a structure represented by Formula 2b: 2b and/or one or more salts thereof, wherein R1 is H or a C1-C6 alkyl group; R2 is selected from H, and a substituted or unsubstituted C1-C6 alkoxy group; R3 is H; and further wherein at least one of R1 and R2 is not H. 8. The compound of claim 7, wherein R1 is a methyl group. 9. The compound of claim 7, wherein R2 is a methoxy group. 10. The compound of claim 7, wherein the compound is selected from Compounds 6 and 7: 11. The compound of claim 2, wherein said compound has a structure represented by Formula 2c: and/or one or more salts thereof, wherein R2 is selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, and a substituted or unsubstituted C1-C6 alkynyl group; R3 is selected from H, a halogen, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, and a substituted or unsubstituted carboxamide; and R4 is selected from H, a substituted or unsubstituted C1-C6 alkyl group, a substituted or unsubstituted C1-C6 alkenyl group, a substituted or unsubstituted C1-C6 alkynyl group, a substituted or unsubstituted C1-C6 alkoxy group, a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, and a substituted or unsubstituted carboxamide; and further wherein at least one of R2 and R3 is not H. 12. The compound of claim 11, wherein R2 is a halogen. 13. The compound of claim 11, wherein R3 is selected from a carboxylic acid, a substituted or unsubstituted C1-C6 carboxy ester, and a substituted or unsubstituted carboxamide. 14. The compound of claim 11, wherein the compound is selected from Compounds 8, 9, 16, and 20: , 8 9 16 20 15. The compound of claim 1, wherein the compound is selected from Compounds 10, 13, 17, 22, 25, 28, 30, 31, 33, 34, 36, and 37: 28 30 16. The compound according to any one of claims 1-15, wherein said salt is formed with a cation selected from H+, Li+, Na+, K+, Mg2+, and Ca2+ and/or said salt is formed with an anion selected from acetate, trifluoromethansulfonate (triflate), halide, trifluoroacetate, formate, H2PO4-, HPO42-, OH-, HSO4-, SO42-, NO3-, HCO3-, and CO32-. 17. The compound according to any one of claims 1-15, wherein said compound is a zwitterion. 18. A composition comprising the compound according to any one of claims 1-17, and a pharmaceutically acceptable excipient or carrier. 19. The composition according to claim 18, wherein said pharmaceutically acceptable excipient or carrier is selected from an anti-adherent, binder, coating, dye, disintegrant, flavoring agent, glidant, lubricant, preservative, sorbent, sweetener, dispersant, diluent, filler, granulating agent, coating agent, wax, suspending agent, wetting agent, and vehicle, and combinations thereof. 20. The composition according to claim 18 or 19, wherein said composition is in a form selected from a tablet, a pill, a capsule, a caplet, a troche, granules, powders, a sachet, a dry powder inhalation form, a chewable, a pastille, a lozenge, an intravenous solution, and a liquid form suitable for infusion or injection. 21. The composition according to any one of claims 18-20, wherein said compound is present as an active pharmaceutical ingredient in a pharmaceutically active amount. 22. The composition according to any one of claims 18-21, further comprising an additional active pharmaceutical ingredient in a pharmaceutically active amount. 23. A method of differentially modulating nicotinamide adenine dinucleotide (NAD) levels in two or more tissues or cell types, said method comprising administering a compound or composition according to any one of claims 1-22, wherein said administering induces a differential response in NAD levels in a first tissue or cell type and a second tissue or cell type. 24. The method of claim 23, wherein said differential response in NAD levels is selected from at least a 10% difference in NAD levels, at least a 20% difference in NAD levels, at least a 30% difference in NAD levels, at least a 40% difference in NAD levels, and at least a 50% difference in NAD levels. 25. The method of claim 23, wherein said differential response in NAD levels is an increase in NAD levels of at least 10% in said first tissue or cell type compared to untreated NAD levels, and a simultaneous decrease in NAD levels of at least 10% in said second tissue or cell type compared to untreated NAD levels. 26. The method of claim 23, wherein said differential response in NAD levels is a maintenance in NAD levels within 10% in said first tissue or cell type compared to untreated NAD levels, and a simultaneous decrease in NAD levels of at least 10% in said second tissue or cell type compared to untreated NAD levels. 27. The method of claim 23, wherein said differential response in NAD levels is a reduction in NAD levels of at least 10% in said first tissue or cell type compared to untreated NAD levels, and a simultaneous decrease in NAD levels in said second tissue or cell type compared to untreated NAD levels, wherein said decrease in said second tissue or cell type is selected from at least 10 percentage points, at least 20 percentage points, at least 30 percentage points, at least 40 percentage points, or at least 50 percentage points more reduction than said reduction in said first tissue or cell type. 28. The method of any one of claims 23-27, wherein said first tissue or cell type is normal tissue or cells, and said second tissue or cell type is neoplastic or cancerous. 29. The method of any one of claims 23-28, wherein said method is a treatment of cancer in an individual in need thereof. 30. The method of any one of claims 23-29, wherein said method exhibits a selective cytostatic or cytotoxic effect, wherein said effect is demonstrated by decreased viability of neoplastic or cancerous tissue or cells compared to untreated neoplastic or cancerous tissue or cells. 31. The method of any one of claims 23-26, wherein said first tissue or cell type is normal tissue or cells, and said method is a treatment for the promotion of the health or increase in biological activity of said first tissue or cell type in an individual in need thereof. 32. The method of claim 31, wherein said treatment does not induce an increase in the risk of a cancer diagnosis in said individual. 33. The method of claim 31, wherein said treatment reduces the risk of a cancer diagnosis in said individual. 34. A method of treating or suppressing cancer in an individual in need thereof, said method comprising administering a compound or composition according to any one of claims 1-22. 35. A method of increasing or maintaining healthy tissue or cells in an individual in need thereof without increasing the risk of growth of neoplastic or cancerous tissue or cells, said method comprising administering a compound or composition according to any one of claims 1-22. 36. A method of increasing or maintaining healthy tissue or cells in an individual in need thereof while suppressing the growth of neoplastic or cancerous tissue or cells, said method comprising administering a compound or composition according to any one of claims 1-22. 37. A method of increasing or maintaining nicotinamide adenine dinucleotide (NAD) levels in at least one healthy tissue or cell type, said method comprising administering a compound or composition according to any one of claims 1-22 to said healthy tissue or cell type. 38. A method of reducing the viability of at least one cancerous tissue or cell type, said method comprising administering a compound or composition according to any one of claims 1-22 to said cancerous tissue or cell type. 39. A method of modulating the level of NAD in at least one tissue or cell type in a mixture of tissues or cell types, said method comprising targeted delivery of a compound or composition according to any one of claims 1-22 to said at least one tissue or cell type. 40. The method of claim 39, wherein said targeted delivery is non-systemic. 41. A method of synthesizing a compound according to any one of claims 1-17, comprising reacting an amine-containing precursor with a nicotinic riboside precursor under conditions to condense said precursors to yield a compound according to any one of claims 1-17. |
In various embodiments, the compounds of Formula 1 are one or more salts, wherein said salts are formed with a cation selected from H + , Li + , Na + , K + , Mg 2+ , and Ca 2+ and/or said salts are formed with an anion selected from acetate, trifluoromethansulfonate (triflate), halide, trifluoroacetate, formate, H2PO4-, HPO4 2- , OH-, HSO4-, SO4 2- , NO3-, HCO3-, and CO3 2- , and mixtures thereof. In various embodiments, the compound is a zwitterion. The present invention includes the use of pharmaceutically acceptable salts of compounds of the invention in the compositions and methods of the present invention. In certain embodiments, contemplated salts of the invention include, but are not limited to, alkyl, dialkyl, trialkyl or tetra-alkyl ammonium salts. In certain embodiments, contemplated salts of the invention include, but are not limited to, L-arginine, benenthamine, benzathine, betaine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2- (diethylamino)ethanol, ethanolamine, ethylenediamine, N-methylglucamine, hydrabamine, 1H-imidazole, lithium, L-lysine, magnesium, 4-(2-hydroxyethyl)morpholine, piperazine, potassium, 1-(2-hydroxyethyl)pyrrolidine, sodium, triethanolamine, tromethamine, and zinc salts. In certain embodiments, the compound is a salt with an anion selected from acetate, triflate, halide, trifluoroacetate, or formate. In other embodiments, if the disclosed compound is in contact with a media, e.g., aqueous media, the anion can be selected from, for example, OH-, H 2 PO 4 -, HPO 4 2- , HSO 4 -, SO 4 2- , NO 3 -, HCO 3 -, and CO 3 2- . In some embodiments, the disclosed compounds are in the form of a negatively charged phosphate, which may form a salt with any suitable cation. The cation can alter as the compound is isolated or transferred into media with different anionic species. For example, a disclosed compound may be in the form of a phosphate salt that is a pharmaceutically acceptable salt as described herein. In certain embodiments, the cation can be selected from Li + , Na + , K + , Mg 2+ , and Ca 2+ . Synthesis In various embodiments, there is disclosed a method of synthesizing a compound as disclosed herein, comprising reacting an amine-containing precursor with a nicotinic riboside precursor under conditions to condense said precursors to yield a compound according to Formulas 1-2c. In certain embodiments, compounds according the invention can be prepared by the condensation of an appropriate nicotinamide or related precursor with 1,2,3,5- tetraacetyl- b-D-ribofuranose. See, for example, Scheme 1. In various embodiments, the synthesis can be performed as a one-pot preparation of crude triol with purification of the product by precipitation. In various embodiments, the synthesis can be performed as a one-pot preparation of crude triol and purification of the product by chromatography. Scheme 1: Preparation of Triols In certain embodiments, the nicotinate starting material can be prepared by condensation of nicotinic acid with, for example an anilide starting material. See, for example, Scheme 2 as an example of amide bond formation in a generic preparation of a nicotinate. Scheme 2: Preparation of Nicotinates Compositions and Pharmaceutical Formulations Provided herein are compositions comprising one or more pharmaceutically acceptable excipients and one or more compounds, and/or salts, thereof, wherein the compound has a structure represented by Formulas 1, 2, 2a, 2b, and/or 2c. Also provided herein are compositions comprising compounds of Formulas 1-2c, including Compounds 1-31. In some embodiments of compositions, the compound is in an amorphous solid form. In other embodiments, the compound is in a crystalline solid form. In some embodiments, the compound is dissolved in a solvent or carrier. In some embodiments, the pharmaceutically acceptable excipient is selected from an anti-adherent, binder, coating, dye, disintegrant, flavoring agent, glidant, lubricant, preservative, sorbent, sweetener, syrups, elixirs, dispersant, diluent, filler, granulating agent, coating agent, wax, suspending agent, wetting agent, thickener and vehicle and combinations thereof. In some embodiments, the excipient is a solid excipient. In some embodiments, the pharmaceutically acceptable excipient is present in an amount of at least about 5% by weight, at least about 10% by weight, at least about 15% by weight, at least about 20% by weight, at least about 25% by weight, at least about 30% by weight, at least about 35% by weight, at least about 40% by weight, at least about 45% by weight, at least about 50% by weight, at least about 55% by weight, or at least about 60% by weight of the composition. In some embodiments, the pharmaceutically acceptable excipient is present in an amount of at least about 20% by weight, at least about 25% by weight, at least about 30% by weight, at least about 35% by weight, or at least about 40% by weight, preferably at least about 30% by weight of the composition. In other embodiments, the pharmaceutically acceptable excipient is present in an amount of at least about 50% by weight of the composition. In some embodiments, the composition is in a solid form selected from a tablet, a pill, a capsule, a caplet, a troche, granules, powders, sachet, dry powder inhalation form, a chewable, a pastille, and a lozenge. In certain embodiments, the composition is in the form of a tablet. In other embodiments, the composition is in a form of a hard or soft gelatin capsule. The compounds of this invention are formulated with conventional carriers and excipients, which can be selected in accord with ordinary practice. Tablets can contain excipients, glidants, fillers, binders and the like. All formulations will optionally contain excipients such as those set forth in the Handbook of Pharmaceutical Excipients (1986). Suitable excipients are also listed in the US Food and Drug Administration Inactive Ingredients Database. Excipients include ascorbic acid and other antioxidants, chelating agents such as EDTA, carbohydrates such as dextran, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid and the like. While it is possible for active pharmaceutical ingredients to be administered alone, it may be preferable to present them as pharmaceutical formulations. The formulations, both for veterinary and for human use, of the invention comprise at least one active ingredient, as above defined, together with one or more acceptable carriers therefor and optionally other therapeutic ingredients. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer’s solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations. Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets, each containing a predetermined amount of the active ingredient as a powder or granules. The active ingredient may also be administered as a bolus, electuary or paste. A tablet is made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent. The tablets may optionally be coated or scored and optionally are formulated so as to provide slow or controlled release of the active ingredient therefrom. Pharmaceutical formulations according to the present invention comprise a compound according to the invention together with one or more pharmaceutically acceptable carriers or excipients and optionally other therapeutic agents. Pharmaceutical formulations containing the active ingredient may be in any form suitable for the intended method of administration. When intended for oral use for example, tablets, troches, lozenges, aqueous or oil suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs may be prepared. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents including sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a palatable preparation. Tablets containing the active ingredient in admixture with non-toxic pharmaceutically acceptable excipient which are suitable for manufacture of tablets are acceptable. These excipients may be, for example, inert diluents, such as calcium or sodium carbonate, lactose, calcium or sodium phosphate; granulating and disintegrating agents, such as maize starch, or alginic acid; binding agents, such as starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid or talc. Tablets may be uncoated or may be coated by known techniques, including microencapsulation, to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed. Formulations for oral use may be also presented as hard gelatin capsules where the active ingredient is mixed with an inert solid diluent, for example calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, such as peanut oil, liquid paraffin or olive oil. Aqueous suspensions of the invention contain the active material(s) in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include a suspending agent, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methylcelluose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; and dispersing or wetting agents such as a naturally-occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethyleneoxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan monooleate). The aqueous suspension may also contain one or more preservatives such as ethyl or n-propyl p-hydroxy-benzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose or saccharin. Liquid formulations may also include eye drops or other forms of delivery to the surface of the eye or adjacent locations such as tear ducts. Liquid formulations may include intravenous formulations, excipients, and carriers such as saline solution, or buffered solution, and the packaging or containers for such formulations, for injection or infusion or the like. Dispersible powders and granules of the invention suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those disclosed above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present. The amount of active ingredient that may be combined with the carrier material to produce a single dosage form will vary depending upon the subject treated and the particular mode of administration. For example, a time-release formulation intended for oral administration to humans may contain approximately 1 to approximately 1000 mg of active material compounded with an appropriate and convenient amount of carrier material which may vary from about 5% to about 95% of the total compositions (weight:weight). The pharmaceutical composition can be prepared to provide easily measurable amounts for administration. Formulations suitable for intrapulmonary or nasal administration have a particle size for example in the range of about 0.1 to about 500 microns, such as about 0.5, about 1, about 30, or about 35 microns etc., which is administered by rapid inhalation through the nasal passage or by inhalation through the mouth so as to reach the alveolar sacs. Suitable formulations include aqueous or oily solutions of the active ingredient. Formulations suitable for aerosol or dry powder administration may be prepared according to conventional methods and may be delivered with other therapeutic agents. The formulations are presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injection, immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets of the kind previously described. Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as herein above recited, or an appropriate fraction thereof, of the active ingredient. It should be understood that in addition to the ingredients particularly mentioned above, the formulations of this invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents. In some embodiments, the amount of the compound of Formulas 1-2c in the composition is about 0.001% by weight up to 100% by weight. In some embodiments, the compound of Formulas 1-2c is the sole active pharmaceutical ingredient in the composition. Alternatively, the compound of Formulas 1- 2c is formulated in a composition with one or more additional active pharmaceutical ingredients. When formulated as the sole active pharmaceutical ingredient, the compound of Formulas 1-2c may be administered individually, or as part of a regimen with one or more separately formulated active pharmaceutical ingredients. When co-administered either in the same formulation or as part of a regimen with one or more separately formulated active pharmaceutical ingredients, the additional active pharmaceutical ingredient may be selected from compounds in the NAD+ pathway, such as nicotinic acid (NA), nicotinamide (Nam), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), nicotinic acid mononucleotide (NaMN), nicotinic acid riboside (NAR), nicotinamide adenine dinucleotide (NAD + /NADH), nicotinamide adenine dinucleotide phosphate (NADP), and nicotinic acid adenine dinucleotide (NaAD). In some embodiments, the additional active pharmaceutical ingredient is an amorphous solid. In some embodiments, the additional active pharmaceutical ingredient is a crystalline solid. In some embodiments, the additional active pharmaceutical ingredient is amorphous NMN. In some embodiments, the additional active pharmaceutical ingredient is crystalline NMN. In some embodiments, the additional active pharmaceutical ingredient is a chemotherapeutic agent selected from 1-amino-4-phenylamino-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate (acid blue 25), 1-amino-4-[4-hydroxyphenyl-amino]-9,10- dioxo-9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[4-aminophenylamino]-9,10-dioxo- 9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[1-naphthylamino]-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate, 1-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo- 9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[2-anthracenylamino]-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate, ABT-263, afatinib dimaleate, axitinib, aminoglutethimide, amsacrine, anastrozole, APCP, asparaginase, AZD5363, Bacillus Calmette–Guérin vaccine (bcg), bicalutamide, bleomycin, bortezomib, b-methylene-ADP (AOPCP), buserelin, busulfan, cabazitaxel, cabozantinib, campothecin, capecitabine, carboplatin, carfilzomib, carmustine, ceritinib, chlorambucil, chloroquine, cisplatin, cladribine, clodronate, cobimetinib, colchicine, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daunorubicin, demethoxyviridin, dexamethasone, dichloroacetate, dienestrol, diethylstilbestrol, docetaxel, doxorubicin, epirubicin, eribulin, erlotinib, estradiol, estramustine, etoposide, everolimus, exemestane, filgrastim, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, gefitinib, gemcitabine, genistein, goserelin, GSK1120212, hydroxyurea, idarubicin, ifosfamide, imatinib, interferon, irinotecan, ixabepilone, lenalidomide, letrozole, leucovorin, leuprolide, levamisole, lomustine, lonidamine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, mesna, metformin, methotrexate, miltefosine, mitomycin, mitotane, mitoxantrone, MK-2206, mutamycin, N-(4-sulfamoylphenylcarbamothioyl) pivalamide, NF279, NF449, nilutamide, nocodazole, octreotide, olaparib, oxaliplatin, paclitaxel, pamidronate, pazopanib, pemexetred, pentostatin, perifosine, PF-04691502, plicamycin, pomalidomide, porfimer, PPADS, procarbazine, quercetin, raltitrexed, ramucirumab, reactive blue 2, rituximab, rolofylline, romidepsin, rucaparib, selumetinib, sirolimus, sodium 2,4-dinitrobenzenesulfonate, sorafenib, streptozocin, sunitinib, suramin, talazoparib, tamoxifen, temozolomide, temsirolimus, teniposide, testosterone, thalidomide, thioguanine, thiotepa, titanocene dichloride, tonapofylline, topotecan, trametinib, trastuzumab, tretinoin, veliparib, vinblastine, vincristine, vindesine, vinorelbine, and vorinostat (SAHA). In other embodiments, suitable chemotherapeutic agents include: FK866, ABT-263, dexamethasone, 5-fluorouracil, PF-04691502, romidepsin, and vorinostat (SAHA). In other embodiments, chemotherapeutic agents include: 1-amino-4-phenylamino-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate (acid blue 25), 1-amino-4-[4-hydroxyphenyl-amino]-9,10- dioxo-9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[4-aminophenylamino]-9,10-dioxo- 9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[1-naphthylamino]-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate, 1-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo- 9,10-dihydroanthracene-2-sulfonate, 1-amino-4-[2-anthracenylamino]-9,10-dioxo-9,10- dihydroanthracene-2-sulfonate, APCP, b-methylene-ADP (AOPCP), capecitabine, cladribine, cytarabine, fludarabine, doxorubicin, gemcitabine, N-(4- sulfamoylphenylcarbamothioyl) pivalamide, NF279, NF449, PPADS, quercetin, reactive blue 2, rolofylline sodium 2,4-dinitrobenzenesulfonate, sumarin, and tonapofylline. Other types of chemotherapeutic agents include immuno-oncology agents such as abagovomab, adecatumumab, afutuzumab, alemtuzumab, anatumomab mafenatox, apolizumab, blinatumomab, BMS-936559, catumaxomab, durvalumab, epacadostat, epratuzumab, indoximod, inotuzumab ozogamicin, intelumumab, ipilimumab, isatuximab, lambrolizumab, MED14736, MPDL3280A, nivolumab, obinutuzumab, ocaratuzumab, ofatumumab, olatatumab, pembrolizumab, pidilizumab, rituximab, ticilimumab, samalizumab, and tremelimumab. In some embodiments, the active pharmaceutical ingredient is selected from PARP inhibitors that are known to repair DNA damage, such as olaparib, veliparib, niraparib, NMS- P118, talazoparib, and rucaparib. Methods of Treatment, Diseases, Disorders and Conditions Provided herein are methods of modulating NAD levels in a subject in need thereof, comprising administering a compound, or a salt thereof, wherein the compound is one disclosed herein, and compositions thereof. Provided herein are methods of treating a disease or disorder associated with NAD biosynthesis, comprising administering a compound, or a salt thereof, wherein the compound is one disclosed herein, and compositions thereof. Provided herein are methods for using the disclosed compounds and pharmaceutical compositions thereof. The disclosed compounds and pharmaceutical compositions thereof can be useful for a variety of therapeutic applications including, for example, treating and/or reducing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing, etc. The methods comprise administering to a subject in need thereof a disclosed compound and/or pharmaceutical composition thereof. The disclosed compounds and pharmaceutical compositions thereof can be useful for increasing or maintaining NAD levels in certain tissues or cells while decreasing NAD levels in other tissues or cells. In various embodiments, the disclosed compounds and pharmaceutical compositions thereof can be used to selectively decrease NAD levels in some tissues or cells, while decreasing NAD levels to a lesser extent in other tissues or cells. In certain embodiments, a compound or pharmaceutical composition as disclosed herein may be used for treating or preventing a disease or condition induced or exacerbated by cellular senescence in a subject; methods for decreasing the rate of senescence of a subject, e.g., after onset of senescence; methods for extending the lifespan of a subject; methods for treating or preventing a disease or condition relating to lifespan; methods for treating or preventing a disease or condition relating to the proliferative capacity of cells; and methods for treating or preventing a disease or condition resulting from cell damage or death. In certain embodiments, the method does not act by decreasing the rate of occurrence of diseases that shorten the lifespan of a subject. In certain embodiments, a method does not act by reducing the lethality caused by a disease, such as cancer. In certain embodiments, a compound or pharmaceutical composition as disclosed herein may be administered to a subject in order to generally increase the lifespan of its cells and to protect its cells against stress and/or against apoptosis. Treating a subject with a compound described herein may be similar to subjecting the subject to hormesis, i.e., mild stress that is beneficial to organisms and may extend their lifespan. The disclosed compounds and pharmaceutical compositions thereof may be administered to subjects who have recently received or are likely to receive a dose of radiation or toxin. In one embodiment, the dose of radiation or toxin is received as part of a work- related or medical procedure, e.g., working in a nuclear power plant, flying an airplane, an X-ray, CAT scan, or the administration of a radioactive dye for medical imaging; in such an embodiment, the compound is administered as a prophylactic measure. In other embodiments, the radiation or toxin exposure is received unintentionally, e.g., as a result of an industrial accident, habitation in a location of natural radiation, terrorist act, or act of war involving radioactive or toxic material. In such a case, the disclosed compounds and pharmaceutical compositions thereof are preferably administered as soon as possible after the exposure to inhibit apoptosis and the subsequent development of acute radiation syndrome. In other embodiments, the disclosed compounds and pharmaceutical compositions thereof may be useful for treating age-related disorders, such as, for example, cancer. Exemplary cancers that may be treated using the disclosed compounds and pharmaceutical compositions thereof include those of the brain and kidney; hormone-dependent cancers including breast, prostate, testicular, and ovarian cancers; lymphomas, and leukemias. Other diseases that can be treated include autoimmune diseases, e.g., systemic lupus erythematosus, scleroderma, and arthritis, in which autoimmune cells should be removed. Viral infections such as herpes, HIV, adenovirus, and HTLV-1 associated malignant and benign disorders can also be treated by administration of the disclosed compounds and pharmaceutical compositions thereof. In some embodiments, the disclosed compounds and pharmaceutical compositions thereof can be used to treat patients suffering from neurodegenerative diseases, and traumatic or mechanical injury to the central nervous system (CNS) or peripheral nervous system (PNS). Examples of neurodegenerative diseases include, but are not limited to, ataxia, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease (HD), amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease), diffuse Lewy body disease, chorea- acanthocytosis, primary lateral sclerosis, ocular diseases (ocular neuritis), chemotherapy- induced neuropathies (e.g., from vincristine, paclitaxel, bortezomib), diabetes-induced neuropathies, and Friedreich’s ataxia. Administration of the disclosed compounds and pharmaceutical compositions thereof may increase insulin sensitivity and/or decrease insulin levels in a subject. A subject in need of such a treatment may be a subject who has insulin resistance or other precursor symptom of type II diabetes, who has type II diabetes, or who is likely to develop any of these conditions. For example, the subject may be a subject having insulin resistance, e.g., having high circulating levels of insulin and/or associated conditions, such as hyperlipidemia, dyslipogenesis, hypercholesterolemia, impaired glucose tolerance, high blood glucose sugar level, other manifestations of syndrome X, hypertension, atherosclerosis, and lipodystrophy. In various embodiments, disclosed herein are methods of differentially modulating nicotinamide adenine dinucleotide (NAD) levels in two or more tissues or cell types. Such methods may comprise administering a compound or composition as disclosed herein, wherein said administering induces a differential response in NAD levels in a first tissue or cell type compared to a second tissue or cell type. In various embodiments, a differential response in NAD levels is selected from at least a 10% difference in NAD levels, at least a 20% difference in NAD levels, at least a 30% difference in NAD levels, at least a 40% difference in NAD levels, at least a 50% difference in NAD levels, at least a 60% difference in NAD levels, at least a 70% difference in NAD levels, at least a 80% difference in NAD levels, at least a 90% difference in NAD levels, at least a 100% difference in NAD levels, at least a 200% difference in NAD levels, at least a 300% difference in NAD levels, at least a 400% difference in NAD levels, at least a 500% difference in NAD levels, at least a 600% difference in NAD levels, at least a 700% difference in NAD levels, at least a 800% difference in NAD levels, at least a 900% difference in NAD levels, and at least a 1000% difference in NAD levels. In various embodiments, a differential response in NAD levels is an increase in NAD levels of at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% in a first tissue or cell type compared to untreated NAD levels or NAD levels before treatment, and a simultaneous decrease in NAD levels of at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% in a second tissue or cell type compared to untreated NAD levels or NAD levels before treatment. In various embodiments, a differential response in NAD levels is a maintenance in NAD levels within 10% in said first tissue or cell type compared to untreated NAD levels, and a simultaneous decrease in NAD levels of at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% in a second tissue or cell type compared to untreated NAD levels. In various embodiments, a differential response in NAD levels is a reduction in NAD levels of at least 10% in a first tissue or cell type compared to untreated NAD levels, and a simultaneous decrease in NAD levels in a second tissue or cell type compared to untreated NAD levels, wherein the decrease in the second tissue or cell type is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% more reduction than the reduction in the first tissue or cell type. In various embodiments, the first tissue or cell type is normal tissue or cells, and the second tissue or cell type is neoplastic or cancerous. Methods of treatment of cancer disclosed herein include treatment of an individual in need thereof. Exemplary cancers that may be treated using the disclosed compounds and pharmaceutical compositions thereof include those of the brain and kidney; hormone- dependent cancers including breast, prostate, testicular, and ovarian cancers; lymphomas, and leukemias. In various embodiments, the cancer may be a common type of cancer in males, such as lung cancer, prostate cancer, colorectal cancer and stomach cancer. In various embodiments, the cancer may be a common type of cancer in females, such as breast cancer, colorectal cancer, lung cancer and cervical cancer. In various embodiments, the cancer may be a skin cancer, such as melanoma, squamous cell carcinoma, or basal cell carcinoma. In various embodiments, the cancer may be a common type of cancer in children, such as acute lymphoblastic leukemia, brain tumors, or non-Hodgkin lymphoma. In various embodiments, the method exhibits a selective cytostatic or cytotoxic effect, wherein the effect is demonstrated by decreased viability of neoplastic or cancerous tissue or cells compared to untreated neoplastic or cancerous tissue or cells. Methods include the situation where a first tissue or cell type is normal tissue or cells, and the method is a treatment for the promotion of the health or increase in biological activity of the first tissue or cell type in an individual in need thereof. In various embodiments, the treatment does not induce an increase in the risk of a cancer diagnosis in a treated individual. Preferably, the treatment reduces the risk of a cancer diagnosis in an individual receiving treatment. Various methods include treating or suppressing cancer in an individual in need thereof, where the method comprises administering a compound or composition as described herein. In various embodiments, disclosed herein are methods of increasing or maintaining healthy tissue or cells in an individual in need thereof without increasing the risk of growth of neoplastic or cancerous tissue or cells, such methods comprising administering a compound or composition as described herein. In various embodiments, described herein are methods of increasing or maintaining healthy tissue or cells in an individual in need thereof while suppressing the growth of neoplastic or cancerous tissue or cells, such methods comprising administering a compound or composition as described herein. In various embodiments, the disclosed methods include methods of increasing or maintaining nicotinamide adenine dinucleotide (NAD) levels in at least one healthy tissue or cell type, such methods comprising administering a compound or composition described herein to the healthy tissue or cell type. In various embodiments, described herein are methods of reducing the viability of at least one cancerous tissue or cell type, such method comprising administering a compound or composition as described herein to the cancerous tissue or cell type. In addition, methods as described herein include methods of modulating the level of NAD in at least one tissue or cell type in a mixture of tissues or cell types, such methods comprising targeted delivery of a compound or composition as described herein to the desired tissue or cell type. In various embodiments, the targeted delivery is non-systemic. While the written description of the invention enables one of ordinary skill to make and use what is considered presently to be the best mode thereof, those of ordinary skill will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiment, method, and examples herein. The invention should therefore not be limited by the described embodiments, methods, and examples, but by all embodiments and methods within the scope and spirit of the invention. EXAMPLES Synthetic Examples General Procedure A: One-pot preparation of crude triol with purification of the product by precipitation (see Example 1) General Procedure B: One-pot preparation of crude triol and purification of the product by chromatography (see Example 9) Example 1: Compound 1 Methyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)benzoate. Trimethylsilyl trifluoromethanesulfonate (TMS-triflate, 4.8 mL, 26.5 mmol, 1.2 eq.) was added dropwise over 5 min. to a stirred mixture of methyl 4-(nicotinamido)benzoate (5.9 g, 23 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (8.1 g, 25.4 mmol, 1.1 eq.) in dry acetonitrile (CH 3 CN, 100 mL) under Ar. The reaction mixture was stirred for 1h at room temperature after which the reaction was determined to be complete after HPLC analysis of an aliquot showed less than 10% of the nicotinamide was present. The reaction mixture was diluted with dry MeOH (50 mL) and concentrated on the rotary evaporator to remove most of the CH 3 CN. The mixture was diluted with MeOH (100 mL) and cooled in an ice bath. Thionyl chloride (SOCl2, 5.8 mL, 80.5 mmol, 3.5 eq.) was added dropwise and the reaction mixture was stirred for 16h in the cold room at 5 o C. The reaction was determined to be complete after HPLC analysis of an aliquot showed less than 5% of the mono and diacetate intermediates present. The crude product was precipitated by adding the solution to 1.3 L of well-stirred MTBE in a 2L Erlenmeyer flask. The precipitated solids were filtered and washed with a large volume of MTBE. After drying on the vacuum funnel, the solids were further dried under high vacuum to afford the product (7.7 g, 62%) as a white solid. 1 H NMR (D2O): d 9.64 (s,1H), 9.28 (d, 1H), 9.04 (d, 1H), 8.29 (dd, 1H), 8.02 (d, 2H), 7.70 (d, 2H), 6.24 (d, 1H), 4.52 (app t, 1H), 4.46 (m, 1H), 4.04 (app dd, 1H), 3.87 (m, 4H or 5H). MS(ESI+) m/z = 389.1 Example 2: Compound 2 N-(4-carbamoylphenyl)-1-((2R,3R,4S,5R)-3,4-dihydroxy-5- (hydroxymethyl)tetrahydrofuran-2-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure A: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-carbamoylphenyl)nicotinamide (1.1 g, 4.6 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq.) in dry acetonitrile (40 mL). The mixture was stirred at room temperature for 2h and after removal of the solvent, treated with 3 eq. of SOCl 2 in 40 mL of MeOH then stirred at 5 o C for 24h. The mixture was concentrated to half the original volume and MTBE (50 mL) was slowly added to precipitate the product. The solids were filtered on a sintered glass funnel and washed with 2 x 10 mL portions of MeOH (pre-cooled to -20 o C ) followed by several portions of MTBE. The solids were dried under high vacuum for several hours to furnish the product (1.25 g, 49%) as a white solid. 1 H NMR (D 2 O): d 9.87 (s, 1H), 9.47 (app d, 1H), 9.17 (app d, 1H), 8.36 (t, 1H), 7.94 (dd, 4H), 6.23 (d, 1H), 4.46 (m, 2H), 4.34 (m, 1H), 3.97 (ab q, 2H). MS(ESI+) m/z = 374.1 Example 3: Compound 3 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4- (methylcarbamoyl)phenyl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.7 mL, 0.55 mmol, 1.2 eq.) was added to a stirred mixture of N-(4(methylcarbamoyl)phenyl)nicotinamide (1.1 0.46 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in dry acetonitrile (40 mL) for 2h. Subsequent workup and treatment with 3 equiv. of SOCl 2 in MeOH, followed by stirring at 5 o C for 24h gave after trituration, the crude product as a semi-solid mass. The material was dissolved in a minimum of 10% MeOH in DCM and loaded onto a 40 g ISCO automated chromatography cartridge. Gradient elution with 5% MeOH in DCM to 30% MeOH in DCM furnished the product (1.1 g, 62%) as a white solid. 1 NMR (D2O): d 11.6 (s, 1H), 9.79 (s, 1H), 9.46 (d, 2H), 9.27 (d, 2H), 8.47 (m, 1H), 8.41 (t, 1H), 7.92 (dd, 4H), 6.25 (d, 1H), 4.40 (t, 1H), 4.27 (m, 1H), 4.18 (t, 1H), 3.79 (ab q, 2H), 2.78 (s, 3H). MS(ESI+) m/z = 388.1 Example 4: Compound 4 ((2R,3S,4R,5R)-3,4-dihydroxy-5-(3-((4-(methoxycarbonyl)pheny l)carbamoyl)-1l 4 -pyridin- 1-yl)tetrahydrofuran-2-yl)methyl hydrogen phosphate. A dry 100 mL flask was charged with 2 g (4.1 mmol) of Compound 1. The flask was flushed with argon and 10 mL of trimethylphosphate was added. The resulting solution was cooled to 0 o C and treated with POCl3 (1.25 g, 8.2 mmol, 2 eq.). The flask was sealed and allowed to stand in the freezer at -10 o C. After 2.5h the homogeneous solution was treated with triethylamine (206 mg, 2.0 mmol) over several minutes and allowed to stand in the freezer overnight. The reaction mixture was cooled in an ice bath and the well-stirred suspension was treated with water (1.5 g, 82 mmol) over several minutes followed solid NaHCO3 (2.4 g, 28.7 mmol) and stirring was continued for 90 min. at 0 o C. The reaction mixture was treated with 100 mL of CH3CN containing 33 mmol of 90% formic acid to produce a white solid. The solid was recovered by filtration, washed with CH3CN and placed under high vacuum to give the crude product as an off-white solid (3.7 g). This material was purified by medium pressure chromatography on a column containing 50 g of aminopropyl functionalized silica. The product was dissolved in 25 mL of 60%/40% MeOH-CH3CN containing 100 mM formic acid and the column was equilibrated with the same solvent mixture. The product containing fractions were combined and concentrated; co-evaporated from water (3 x 25 mL), frozen and lyophilized to give the product (300 mg, 16%) as a white solid. 1 H NMR (D2O): d 9.4 (s, 1H), 9.2 (m, 1H), 8.9 (d, 1H), 8.2 (m, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.1 (d, 1H), 4.6 (m, 1H), 4.5 (m, 1H), 4.4 (q, 1H), 4.2 (dq, 1H), 4.1 (dq, 1H), 3.8 (s, 3H). 31 P NMR (D 2 O): 0.24 ppm. MS(ESI+) m/z = 468.1 Example 5: Compound 5 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(1-oxo-1,3- dihydroisobenzofuran-5-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (1-oxo-1,3-dihydroisobenzofuran-5-yl) nicotinamide (1.2 g, 4.7 mmol) and 1,2,3,5- tetraacetyl- b-D-ribofuranose (1.1 eq.) in dry acetonitrile (40 mL) for 2h. Evaporation of the solvent and treatment with SOCl 2 (3 eq.) in MeOH (40 mL) followed by stirring for 24h at 5 o C and subsequent workup gave the crude product as a semi-solid mass. The crude product was dissolved a minimum of 5% MeOH in DCM and loaded onto a 24 g ISCO cartridge. Gradient elution with 5% MeOH in DCM to 30% MeOH in DCM furnished the product (1.75 g, 67%) as a white solid. 1 H NMR (D2O): d 9.63 (s, 1H), 9.26 (d, 1H), 9.04 (d, 1H), 8.28 (t, 1H), 7.86 (s, 1H), 7.75 (d, 1H), 7.59 (d, 1H), 6.23 (d, 1H), 4.52 (t, 1H), 4.44 (m, 1H), 4.34 (t, 1H), 3.95 (ab q, 2H). MS(ESI+) m/z = 387.1 Example 6: Compound 6 Methyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-N- methyl-1l 4 -pyridine-3-carboxamido)benzoate. A dry 100 mL RB was charged with the 3.2 g methyl 4-(N-methylnicotinamido) benzoate (11.8 mmol) and the flask flushed with argon. Under a flow of argon, this was dissolved in 35 mL anhydrous dioxane and treated with 3.8 g of ribose tetraacetate (11.8 mmol). The resulting solution was briefly cooled on ice water and treated with 3.2 g TMS-triflate (14.2 mmol), allowed to warm to ambient temperature and stirred. After 2.5 hours, the reaction proceeded to ~90% completion. The solvent was removed by rotary evaporation and the residue was taken up 50 mL DCM. This was washed with saturated NaHCO3 and brine. The aqueous layer was back-extracted with DCM, the organic layers were combined, and dried over Na2SO4, filtered and evaporated under high-vacuum to yield 6.9 g of an off-white foam. This was purified on a medium-pressure LC system using a 120 g silica cartridge with a gradient of 0-15% MeOH in DCM. The product fractions were isolated pooled, stripped, and placed on high vac to give the triacetate, 5.6 g (70%). 1 H NMR (CDCl3): d 9.3 (bd s, 1H); 9.2 (d, 1H); 8.0 (d, 2H); 7.3 (d, 2H); 6.6 (d, 1H); 5.3 (m, 1H); 5.2 (m, 1H); 4.7 (m, 1H); 4.5 (dd, 1H); 4.4 (dd, 1H); 3.9 (s, 3H); 3.6 (s, 3H); 2.2 (s, 3H); 2.1 (s, 3H); 2.0 (s, 3H). A 250 mL RB was charged with 5.6 g of the above triacetate (8.2 mmol) and the flask flushed with argon. This was dissolved in 75 mL anhydrous MeOH, the resulting solution cooled on ice, and treated dropwise with 2.94 g of SOCl 2 (24.7 mmol). The sealed reaction vessel was allowed to stand in the refrigerator at 10 o C. After 18 hours, the solvent was removed in vacuo and the residue was triturated with MTBE, then placed on high vacuum to give, 4.7 g as a white solid. This was purified on a 40 g silica ISCO cartridge, using a gradient of 0-15% MeOH in DCM. The product fractions were pooled and stripped to give, 2.5 g as an off- white foam. 1 H NMR (CDCl 3 ): d 9.0 (d, 1H); 8.1 (d, 1H); 7.8 (m, 3H); 7.2 (d, 2H); 5.8 (d, 1H); 4.2 (m, 2H); 4.1 (d, 2H); 3.8-3.6 (4H); 3.4 (s, 3H); 3.2 (s, 3H). Example 7: Compound 7 Methyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)-3-methoxy-benzoate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 3-methoxy-4-(nicotinamido)benzoate (1.6 g, 5.63 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq.) in dry acetonitrile (40 mL) and the resultant mixture was stirred for 2h. Workup as previously described and subsequent treatment with 3 equiv. of SOCl 2 in MeOH, followed by stirring at 5 o C for 24h gave after trituration, the crude product as a semi-solid mass. The crude product was purified using the ISCO (40 g cartridge) eluting with a gradient of DCM to 30% MeOH in DCM to afford the product (715 mg, 23%) as an off-white solid. 1 H NMR (CD3OD): d 9.84 (s, 1H), 9.67 (d, 1H), 9.12 (d, 1H), 8.31-8.36 (m, 2H), 7.72-7.74 (m, 2H), 6.25 (d, 1H), 4.42-4.52 (m, 2H), 4.36 (m, 1H), 4.04 (s, 3H), 3.96 (ab q, 2H), 3.91 (s, 3H). MS(ESI+) m/z = 419.1 Example 8: Compound 8 Methyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1 l 4 - pyridine-3-carboxamido)-3-fluorobenzoate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 3-fluoro-4-(nicotinamido)benzoate (610 mg, 2.31 mmol) and 1,2,3,5-tetraacetyl b- -D- ribofuranose (800 mg, 2.5 mmol, 1.1 eq.) in dry acetonitrile (40 mL) and the mixture was stirred for 2h at ambient temperature. The solvent was evaporated under reduced pressure and the residue was treated with 3 equiv. of SOCl2 in MeOH, followed by stirring at 5 o C for 24h. Workup as previously described gave the crude product as a semi-solid mass after removal of excess HCl by co-evaporation with DCM. The crude product was purified on the ISCO (24 g cartridge) eluting with a gradient of DCM to 30% MeOH in DCM to afford the product (400 mg, 31%) as a tan solid. 1 H NMR (CD3CN): d 9.66 (S, 1H), 9.30 (br s, 1H), 9.26 (d, 1H), 8.98 (d, 1H), 8.26 (t, 2H), 7.93 (d, 1H), 7.87 (d, 1H), 6.14 (d, 1H), 4.47 (t, 1H), 4.13 (m, 1H), 3.94 (ab q, 2H, 3.92 (s, 1H). MS(ESI+) m/z = 407.1 Example 9: Compound 9 Ethyl 3-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1 l 4 - pyridine-3-carboxamido)benzoate. TMS-triflate (2.9 mL, 15.7 mmol, 1.2 eq.) was added dropwise to a stirred mixture of ethyl 3-(nicotinamido)benzoate (3.85 g, 14.3 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (8.1 g, 25.4 mmol, 1.1 eq.) in dry DCM (80 mL) under Ar. The reaction mixture was stirred for 1h at room temperature, after which the reaction was found to be only 10% complete by HPLC analysis of due to insolubility of the nicotinamide. The reaction mixture was diluted with dry dioxane (30 mL) and additional TMS-triflate (3.0 mL, 1.1 eq.) was added. The reaction mixture was stirred for 1h and at that time, was found to be complete by HPLC analysis. The mixture was concentrated on the rotary evaporator to approximately 20 mL, diluted with anhydrous absolute EtOH (50 mL), cooled in an ice bath and treated dropwise with SOCl2 (4.2 mL, 57.3 mmol, 4 eq.). The mixture was stirred for 3 days in the cold room at 5 o C, then concentrated on the rotary evaporator to approximately 30 mL and triturated with MTBE to precipitate the crude product as a semi-solid mass. The product was further triturated with MTBE to afford an off-white solid (2 g).1 g of this material was purified on the ISCO Combi Flash® automated chromatography system using a 24 g silica gel cartridge and loading with a minimum of 5% MeOH in DCM. Elution was performed using a gradient of 5% MeOH in DCM to 30% MeOH in DCM. The pure fractions were pooled and concentrated, then co-stripped with DCM to give, after placing under high vacuum for several hours, the pure product (700 mg, 24% overall yield) as a white solid. 1 H NMR (D 2 O): d 9.64 (s, 1H), 9.30 (d, 1H), 9.04 (d, 1H), 8.42 (s, 1H), 8.27 (app t, 1H), 7.94 (d, 1H), 7.85 (d, 1H), 7.85 (d, 1H), 7.55 (t, 1H), 6.16 (d, 1H), 4.46 (app t, 1H), 4.33-4.43 (m, 2 or 3H), 4.31 (app t, 1H), 3.92 (ab q, 2H), 1.97 (q, 2H). MS(ESI+) m/z = 403.1 Example 10: Compound 10 Ethyl 2-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)benzoate. Trimethylsilyl trifluoromethanesulfonate (TMS-triflate, 3.3 mL, 17.8 mmol, 1.2 eq.) was added dropwise over 5 min. to a stirred mixture of methyl 2-(nicotinamido)benzoate (3.8 g, 14.8 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (5.2 g, 16.3 mmol, 1.1 eq.) in dry DCM (35 mL) under Ar. The reaction mixture was stirred for 1.5h at ambient temperature and the reaction was determined to be complete by HPLC. The mixture was cooled in an ice bath, diluted with dry MeOH (50 mL) and thionyl chloride (SOCl2, 3.22 mL, 44.4 mmol, 3 eq.) was added dropwise. The solution was allowed to stand in the cold room at 5 o C for 24h. The mixture was concentrated to approximately 20 mL on the rotary evaporator and the product was precipitated by the addition of 100 mL of MTBE. After decanting the solution, the residue was twice triturated with MTBE to afford a tan solid. Attempted purification of a 2 g sample by chromatography was not successful leading to decomposition of the product on the column.1.2 g of the solid was dissolved in anhydrous absolute EtOH (10 mL) and the product was precipitated by the addition of 40 mL of MTBE. After successive trituration with MTBE, the solids were collected by filtration and washed with MTBE. After drying under high vacuum overnight, the product (780 mg) was obtained as an off-white solid with a purity of 95%. 1 H NMR (DMSO-d 6 ): d 11.74 (s, 1H), 9.80 (s, 1H), 9.52 (d, 1H), 9.13 (d, 1H), 8.45 (t, 1H), 8.21 (d, 1H), 8.03 (d, 1H), 7.74 (t, 1H), 7.38 (t, 1H), 6.29 (d, 1H), 4.38 (t, 1H), 4.23 (m, 1H), 3.88 (s, 3H). MS(ESI+) m/z = 389.1 Example 11: Compound 11 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4- (hydroxymethyl)phenyl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-(methoxymethyl)phenyl)nicotinamide (0.50 g, 1.95 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq) in dry CH 3 CN (20 mL). After stirring for 2h at ambient temperature the solvent was evaporated and residue was taken up in anhydrous MeOH (20 mL), cooled in ice bath and treated with SOCl2 (3.5 eq.) After stirring for 16h at 5 o C, HPLC analysis showed approximately 20% of the mono acetate intermediate still present so additional SOCl2 (1 eq.) was added and stirring was continued for 8h at 5 o C. After workup and purification of the crude product on the ISCO, the product (405 mg, 13%) was isolated as a light yellow solid. 1 H NMR (D2O): d 9.63 (s, 1H), 9.25 (d, 1H), 9.02 (d, 1H), 8.26 (app t, 1H), 7.54 (m, 2H), 7.43 (d, 1H), 7.34 (d, 1H), 6.24 (d, 1H), 4.50 (t, 1H), 4.46 (m, 1H), 4.35 (s, 2H), 3.95 (ab q, 2H). MS(ESI+) m/z = 361.1 Example 12: Compound 12 N-(4-(diethylcarbamoyl)phenyl)-1-((2R,3R,4S,5R)-3,4-dihydrox y-5- (hydroxymethyl)tetrahydrofuran-2-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-(diethylcarbamoyl)phenyl)nicotinamide (1.4 g, 4.7 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.15 eq.) in DCM (50 mL) followed by 3h of stirring. Subsequent treatment with SOCl2 (3 eq.) in MeOH and stirring at 5 o C for 16h gave after workup as previously described, the crude product as a semi-solid mass. The residue was taken up in a minimum of 15% MeOH in DCM and loaded onto a 40 g ISCO column eluting with a gradient of 10% MeOH in DCM to 40% MeOH in DCM to afford the product (1.15 g, 57%) as an off-white solid. 1 H NMR (D 2 O): d 9.67 (s, 1H), 9.27 (d, 1H), 9.05 (d, 1H), 8.29 (t, 1H), 7.67 (d, 2H), 7.46 (d, 2H), 6.24 (d, 1H), 4.53 ( app t, 1H), 4.46 (m, 1H), 4.36 (t, 1H), 3.95 (ab q, 2H), 3.53 (q, 2H), 3.29 (q, 2H), 1.23 (t, 3H), 1.09 (t, 3H). MS(ESI+) m/z = 430.2 Example 13: Compound 13 N-(4-cyanophenyl)-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxym ethyl)tetrahydrofuran-2- yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-cyanophenyl)nicotinamide (1.5 g, 5.63 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in DCM (40 mL) followed by 3h of stirring at ambient temperature. Evaporation of the solvent followed by treatment with SOCl 2 (3 eq.) in MeOH and stirring at 5 o C for 16h gave after workup as previously described, the crude product as a semi-solid mass. The residue was taken up in a minimum of 20% MeOH in DCM and loaded onto a 40 g ISCO column eluting with a gradient of 10% MeOH in DCM to 40% MeOH in DCM to afford 1.15 g (57%) of the pure product as an off-white solid. 1 H NMR (D2O): d 9.66 (s, 1H), 9.27 (d, 1H), 9.04 (d, 1H), 8.28 (t, 1H), 7.75 (m, 4H), 6.25 (d, 1H), 4.52 (t, 1H), 4.46 (m, 1H), 4.34 (app t, 1H), 4.03 (dd, 1H), 3.95 (ab q, 2H). MS(ESI+) m/z = 356.1 Example 14: Compound 14 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4- (trifluoromethyl)phenyl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.5 mL, 8.04 mmol, 1.2 eq.) was added to a stirred mixture of N-(4-(trifluoromethyl)phenyl)nicotinamide (1.5 g, 6.7 mmol) and 1,2,3,5- tetraacetyl- b-D-ribofuranose (2.4 g, 7.4 mmol, 1.1 eq.) in DCM (40 mL). Subsequent treatment with SOCl2 (3 eq.) in MeOH and stirring at 5 o C for 16h followed by workup as previously described, gave the crude product as an off-white solid. One half of this material was chromatographed on the ISCO (40 g cartridge, elution with a gradient of DCM to 30% MeOH in DCM) to give the product (300 mg) as a white solid. 1 H NMR (D2O): d 9.66 (s, 1H), 9.27 (d, 1H), 9.04 (d, 1H), 8.28 (t, 1H), 7.75 (m, 4H), 6.25 (d, 1H), 4.52 (t, 1H), 4.46 (m, 1H), 4.34 (app t, 1H), 4.03 (dd, 1H), 3.95 (ab q, 2H). MS(ESI+) m/z = 399.1 Example 15: Compound 15 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 -pyridine- 3-carboxamido)benzoic acid. To a mixture of 4-(nicotinamido)benzoic acid (3.76 g, 9.59 mmol) and 1,2,3,5-tetraacetyl- b- D-ribofuranose (3.20 g, 10.07 mmol) in dry dioxane (40 mL) was added triethylamine (4.02 mL, 28.8 mmol, 3 eq.) and the mixture was stirred for 15 minutes at room temperature. TMS- triflate (6.94 mL, 38.4 mmol, 3 eq.) was added over 5 minutes and the reaction was allowed to stir for 20 min, whereupon HPLC analysis showed the reaction to be complete. The mixture was diluted with 40 mL of MTBE and the solution was poured into 300 mL of MTBE and the resultant oil was allowed to settle. After decanting the solvent, the oil was triturated twice with 80 mL portions of MTBE. The residue was dissolved in EtOAc (50 mL) and washed with 2 x 30 mL portions of water and dried over anhydrous Na 2 SO 4 . Filtration and evaporation of the solvent yielded 5.5 g of the crude triacetate intermediate. 2.23 g of this material was chromatographed on 600 g of silica gel eluting with a gradient of 5% MeOH in DCM to 30% MeOH in DCM to provide the purified triacetate (1.3 g) as a white solid. Triacetate: 1 H NMR (CD3CN): d 9.68 (br s, 1H), 9,48 (d, 1H), 9.14 (d, 1H), 9.09 (dd, 1H), 8.33 (dd, 1H), 8.10 (d, 2H), 7.92 (d, 2H), 6.45 (m, 1H), 5.53 (d, 1H), 5.43 (t, 1H), 4.81 (q, 1H), 4.53 (dd, 1H), 4.50 (dd, 1H), 2.19 (s, 3H), 2.14 (s, 3H), 2.11 (s, 3H). The triacetate (1.3 g, 2.0 mmol) was dissolved in 4 mL of dry MeOH and was added to a well-stirred ice-cold solution of 1N NaOMe in MeOH (6 mL, 6.0 mmol, 3 eq.) under Ar. The mixture was stirred for 20 min. then a cold solution 1N HCl in MeOH (6 mL, 6.0 mmol, 3 eq.) was added all at once. The color of the solution changed from dark orange to yellow and a solid precipitated from solution (the pH of the solution was 2). The product was filtered and washed generously with MTBE then dried under high vacuum to provide the product (369 mg, 49%) as a light pink solid. 1 H NMR (D 2 O): d 9.65 (s, 1H), 9.27 (d, 1H), 9.03 (d, 1H), 8.28 (t, 1H), 8.01 (q, 2H), 7.71 (br d, 2H), 6.25 (d, 1H), 4.52 (t, 1H), 4.47 (q, 1H), 4.35 (t, 1H), 4.03 (dd, 1H), 3.88 (dd, 1H). MS(ESI+) m/z = 375.1 Example 16: Compound 16 Methyl 2-chloro-4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl) tetrahydrofuran-2- yl)-1l 4 -pyridine-3-carboxamido)benzoate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 2-chloro-4-(nicotinamido)benzoate (610 mg, 2.31 mmol) and 1,2,3,5-tetraacetyl- b- D-ribofuranose (1.1 eq.) in DCM (40 mL). After stirring for 2h, 20 mL of dry CH 3 CN was added to give a clear solution and the reaction mixture was stirred an additional hour at ambient temperature. The solvent was removed under reduced pressure and the residue was dissolved in MeOH, cooled and treated with SOCl 2 (3 eq.) in MeOH. The mixture was stirred for 16h and workup as described previously furnished the crude product which was purified on the ISCO to afford a white solid (600 mg, 26%). 1 H NMR (D 2 O): d 9.64 (s, 1H), 9.28 (d, 1H), 9.03 (d, 1H), 8.29 (app t, 1H), 7.87 (d, 1H), 7.82 (d, 1H), 7.57 (dd, 1H), 6.24 (d, 1H), 4.52 (app t, 1H), 4.46 (m, 1H), 4.34 (app t, 1H), 4.03 (app dd, 1H), 3.95 (ab q, 2H). MS(ESI+) m/z = 423.1 Example 17: Compound 17 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4-(oxazol-2- yl)phenyl)-1 l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-(oxazol-2-yl)phenyl)nicotinamide (900 mg, 3.4 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.2 g, 3.73 mmol, 1.1 eq.) in dry acetonitrile (40 mL) for 2h. After removal of the solvent under reduced pressure the residue was dissolved in MeOH and treated with 3 eq. of SOCl2 and stirred at 5 o C for 16h. Subsequent workup as previously described, gave the crude product as a tan solid. Purification on the ISCO (40 g cartridge, gradient elution with DCM to 30% MeOH in DCM) afforded the product as a white solid (650 mg, 48%). 1 H NMR (D2O ): d 11.74 (br s, 1H), 9.81(br s, 1H), 9.46 (d, 1H), 9.26 (d, 1H), 8.40 (t, 1H), 8.23 (d, 1H), 8.03-8.12 (m, 5H), 7.37 (br s, 1H), 6.25 (d, 1H), 4.43 (t, 1H), 4.28 (m, 1H), 4.20 (t, 1H), 3.79 (ab q, 2H). MS(ESI+) m/z = 398.1 Example 18: Compound 18 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(2-methyl-1,3- dioxoisoindolin-5-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.91 mL, 10.34 mmol, 1.2 eq.) was added to a stirred mixture of N-(2-methyl-1,3-dioxoisoindolin-5-yl)nicotinamide (2.46 g, 8.75 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (3.04 g, 9.56 mmol, 1.1 eq.) in CH 3 CN (80 mL). After stirring for 3h at ambient temperature followed by removal of the solvent and treatment with SOCl 2 (3 eq.) in MeOH and stirring for 16h, the crude product was obtained as a tan solid after trituration with MTBE. Purification was accomplished on the ISCO (40 g cartridge, elution with a gradient of DCM to 30% MeOH in DCM). After combining the pure fractions and evaporation of the solvents under reduced pressure, the product (1.05 g, 29%) was obtained as an off-white solid. 1 H NMR (D2O ): d 9.69 (s, 1H), 9.31 (d, 1H), 9.07 (d, 1H), 8.34 (t, 1H), 8.08 (s, 1H), 7.83 (dd, 2H), 6.26 (d, 1H), 4.53 (t, 1H), 4.46 (m, 1H), 4.36 (t, 1H), 3.95 (ab q, 2H), 3.07 (s, 3H). MS(ESI+) m/z = 414.1 Example 19: Compound 19 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(2-methyl-3- oxoisoindolin-5-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (2-methyl-3-oxoisoindolin-5-yl) nicotinamide (1.25 g, 4.7 mmol) and 1,2,3,5-tetraacetyl- b- D-ribofuranose (1.1 eq.) in dry CH3CN (50 mL). After stirring for 3h at ambient temperature followed by evaporation of the solvent and treatment with SOCl 2 (3 eq.) in MeOH for 24h at 5 o C, the crude product was obtained as an off-white solid after trituration. Purification on the ISCO (40 g cartridge, elution with a gradient of DCM to 40 % MeOH in DCM) afforded the pure product (650 mg, 35%) as a white solid. 1 H NMR (D 2 O): d 9.65 (s, 1H), 9.28 (d, 1H), 9.04 (d, 1H), 8.30 (t, 1H), 7.83 (s, 1H), 7.83 (s, 1H), 7.66 (d, 1H), 7.57 (d, 1H), 6.26 (d, 1H), 5.42 (s, 1H), 4.53 (t, 1H), 4.46 (m, 1H), 3.95 (ab q, 2H), 3.10 (s, 1H). MS(ESI+) m/z = 400.2 Example 20: Compound 20 N-(3-carbamoylphenyl)-1-((2R,3R,4S,5R)-3,4-dihydroxy-5- (hydroxymethyl)tetrahydrofuran-2-yl)-1l 4 -pyridine-3-carboxamide. TMS-triflate (1.3 mL, 7.1 mmol, 1.2 eq.) was added to a stirred mixture of N-(3- carbamoylphenyl)nicotinamide (1.42 g, 6.75 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (2.2 g, 6.8 mmol, 1.1 eq.) in CH3CN (60 mL) at room temperature. After stirring for 2h, the solvent was removed and the residue was taken up in ethyl acetate. The solution was transferred to a separatory funnel and washed sequentially with an aqueous solution of 5% NaHCO 3 , water and brine then dried over anhydrous Na 2 SO 4 . The solution was filtered and concentrated and the residue was purified on the ISCO (40 g cartridge) eluting with DCM to 20% MeOH in DCM. The fractions containing the product were pooled and concentrated to give the triacetate intermediate (405 mg) as a foam. This material was dissolved in dry MeOH (20 mL), cooled in an ice bath and treated with 3 equiv. of SOCl 2 . The solution was stirred at 5 o C for 24h. The solution was triturated with MTBE to precipitate the product as a white solid which was collected by filtration. The product was washed on the vacuum funnel with several portions of MTBE then placed under high vacuum to remove traces of HCl. The product (140 mg, 6%) was obtained as a white solid. 1 H NMR (D2O): ^ d 9.68 (s, 1H), 9.28 (d, 1H), 9.05 (d, 1H), 8.29 (t, 1H), 7.97 (s, 1H), 7.76 (d, 1H), 7.68 (d, 1H), 7.56 (t, 1H), 6.25 (d, 1H), 4.51 (app t, 1H), 4.47 (m, 1H), 4.36 (t, 1H), 3.95 (ab q, 2H). MS(ESI+) m/z = 374.1 Example 21: Compound 21 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(3-oxo-1,3- dihydroisobenzofuran-5-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure B: TMS-triflate (0.75 mL, 4.1 mmol, 1.2 eq) was added to a stirred mixture of N-(3-oxo-1,3-dihydroisobenzofuran-5-yl) nicotinamide (0.85 g, 3.4 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.2 g, 3.7 mmol, 1.1 eq.) in CH 3 CN (25 mL). After stirring for 1.5h at ambient temperature followed by removal of the solvent and treatment with SOCl 2 (3.5 eq.) in MeOH, the solution was stirred for 24h at 5 o C. MTBE was added slowly to the solution to precipitate the crude product which was triturated with MTBE and the residue co-stripped with DCM followed by CH 3 CN to remove traces of HCl. The residue was dissolved in a minimum of 20% MeOH in DCM and loaded onto a 24 g ISCO cartridge. Elution with 5% to 30% MeOH in DCM followed by evaporation of the pure fractions gave the pure product (505 mg, 38%). 1 H NMR (D2O): d 9.68 (s, 1H), 9.28 (d, 1H), 9.06 (d, 1H), 8.32 (t, 1H), 8.12 (s, 1H), 7.89 (d, 1H), 7.66 (d, 1H), 6.26 (d, 1H), 5.43 (s, 2H), 4.54 (t, 1H), 4.46 (m, 1H), 4.36 (t, 1H). MS(ESI+) m/z = 387.1 Example 22: Compound 22 Methyl 1-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carbonyl)indoline-5-carboxylate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 1-nicotinoylindoline-5-carboxylate (0.5 g, 1.78 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq.) in CH3CN (16 mL). After stirring for 2h at ambient temperature the solvent was removed and the residue was dissolved in MeOH, cooled and treated with SOCl 2 (3 eq.). After stirring for 16h at 5 o C the crude product was obtained after trituration with MTBE as an off-white solid. Purification was accomplished in the normal fashion on the ISCO (40 g cartridge, elution with a gradient of 10% MeOH in DCM to 30 % MeOH in DCM) to furnish the product (330 mg, 45%) as an off-white solid. 1 H NMR (D2O): d 9.45 (br s, 1H), 9.25 (d, 1H), 8.85 (d, 1H), 8.3 (t, 1H), 7.70-8.10 (m, 3H), 6.23 (br s, 1H), 4.47 (m, 2H), 4.35 (m, 1H), 3.92 -4.20 (m, 3H), 3.85 (s, 3H), 3.16 (m, 2H). MS(ESI+) m/z = 415.2 Example 23: Compound 23 Methyl (4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahyd rofuran-2-yl)-1l 4 - pyridine-carboxamido)benzoyl)glycinate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl (4-(nicotinamido)benzoyl)glycinate (0.5 g, 1.6 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq.) in CH3CN (15 mL). After stirring for 2h at ambient temperature, removal of the solvent and treatment with SOCl 2 (3.5 eq.) in MeOH, the solution was stirred for 16h at 5 o C. HPLC at that time showed 10% of the mono-acetate remaining so additional SOCl2 (0.1 mL) was added and stirring was continued for 6h. The crude product was obtained after trituration with MTBE as an off-white solid. Purification on the ISCO (12 g cartridge, elution with a gradient of 5% MeOH in DCM to 30 % MeOH in DCM) furnished the product (155 mg, 22 %) as an off-white solid. 1 H NMR (D2O): d 9.65 (br s, 1H), 9.26 (d, 1H), 9.03 (m, 1H), 8.27 (t, 1H), 7.65-7.88 (m, 4H), 6.24 (d, 1H), 4.50 (t, 1H), 4.45 (t, 1H), 4.35 (m, 1H), 4.15 (br s, 1H), 3.95 (ab q), 3.75 (s, 3H). MS(ESI+) m/z = 446.2 Example 24: Compound 24 Ethyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)benzoate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of ethyl 4-(nicotinamido)benzoate (0.5 g, 1.85 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in CH3CN (20 mL). After stirring for 3h at ambient temperature the solvent was evaporated and residue was taken up in anhydrous absolute EtOH (20mL) and cooled in an ice bath. SOCl2 (3.5 eq.) was added dropwise and the solution was allowed to stand at 5 o C for 72h. Workup as previously described gave the crude product as a semi-solid mass. The crude product was purified on the ISCO (24 g cartridge, loading with 10% MeOH in DCM) eluting with a gradient of 5-30% MeOH in DCM over 15 min. The pure fractions were pooled, stripped and traces of solvent were removed under high vacuum. The product (145 mg, 19%) was obtained as an off-white solid. 1 H NMR (DMSOd6): d 11.75 (s, 1H), 9.79 (s, 1H), 9.46 (d, 1H), 8.38 (t, 1H), 8.04 (m, 4H), 6.24 (d, 1H), 4.42 (t, 1H), 4.22-4.35 (m, 3H), 4.18 (t, 1H), 3.80 (ab q, 2H), 1.33 (t, 3H). MS(ESI+) m/z = 403.2 Example 25: Compound 25 Methyl 5-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)picolinate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 5-(nicotinamido)picolinate (1.21 g, 4.8 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq) in CH3CN (50 mL). After stirring for 3h at ambient temperature, the solvent was evaporated and residue was taken up in anhydrous MeOH (40 mL), cooled in an ice bath and treated with SOCl 2 (3.5 eq.) After stirring at 5 o C for 24h, the solution was concentrated to 10 mL and the product was precipitated with MTBE. The product was filtered through a sintered glass funnel and washed sequentially with 2 x 5 mL portions of ice-cold MeOH then an excess of MTBE. After removing traces of solvent under high vacuum, the product (650 mg, 35%) was isolated as a white solid. 1 H NMR (D 2 O): d 9.63 (s, 1H), 9.26 (d, 1H), 9.03 (d, 1H), 8.26 (app t, 1H), 7.84 (br s, 1H), 7.70 (m, 1H), 7.59 (m, 1H), 6.23 (d, 1H), 4.47 (t, 1H), 4.42 (s, 3H), 4.33 (app t, 1H), 3.94 (ab q, 2H). MS(ESI+) m/z = 390.1 Example 26: Compound 26 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(1- oxoisoindolin-5-yl)-1l 4 -pyridine-3-carboxamide. Following General Procedure A: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (1-oxoisoindolin-5-yl)nicotinamide (0.56 g, 2.2 mmol) and 1,2,3,5-tetraacetyl- d-D- ribofuranose (1.1 eq) in CH 3 CN (20 mL). After stirring for 1.5h at ambient temperature, the solvent was evaporated and residue was taken up in anhydrous MeOH (20 mL) and cooled in an ice bath. SOCl 2 (3.5 eq.) was added dropwise and the solution was stirred at 5 o C for 18h. The product was precipitated with MTBE, the solvents were decanted and the solids were re-dissolved in MeOH and precipitated with MTBE. After trituration with MTBE, the solids (hygroscopic) were co-evaporated with CH3CN to remove traces of water and HCl. The pure product (600 mg, 71%) was obtained as an off-white solid. 1 H NMR (DMSO-d6): d 11.9 (br s, 1H), 9.81 (d, 1H), 9.27 (app d, 1H), 9.16 (app d, 1H), 8.48 (m, 1H), 8.43 (app t, 1H), 8.18 (d, 1H), 6.24 (d, 1H), 4.40 (app t, 1H), 4.29 (m, 1H), 4.19 (app t, 1H), 3.87 (s, 2H), 3.81 (ab q, 2H). MS(ESI+) m/z = 386.1 Example 27: Compound 27 2-(dimethylamino)ethyl 4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetra hydrofuran-2-yl)-1l 4 -pyridine-3-carboxamido)benzoate. TMS-triflate (3.0 g, 13.7 mmol) was added over 5 min. to a stirred solution of 2- (dimethylamino)ethyl 4-(nicotinamido)benzoate (1.8 g, 5.7 mmol) and 1,2,3,5-tetraacetyl- b- D-ribofuranose (1.8 g, 5.7 mmol) in 40 mL of DCM in an ice bath. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The solvent was stripped and the residue was dissolved in EtOAc. This was washed with water, saturated NaHCO 3 and brine, then dried over Na2SO4 and evaporated to dryness under vacuum to give 2.5 g of the triacetate as a solid. This compound was dissolved in 25 mL of dry MeOH and after cooling in an ice bath was treated with 1.63 g (20.8 mmol, 3.65 eq.) of acetyl chloride dropwise. The mixture was placed under argon and allowed to stand at 10 o C overnight then was allowed to warm to ambient temperature and stirred for 3h. The solvent was stripped to near dryness and the residue was triturated with hexanes (2 x 150 mL) followed by MTBE (3 x 100 mL). The residue was taken up in MeOH (10 mL) and evaporated under high vacuum to give 2.1 g of a solid. The solid was suspended in 250 mL of acetone and treated with aqueous 5% NaHCO3 to neutrality. After standing in the freezer for several hours, the mixture was filtered, the filtrate was evaporated to an oil, frozen and lyophilized to give the product (650 mg, 43%) as a brown solid. 1 H NMR (D 2 O/CD 3 CN): d 10.0 (s, 1H), 9.6 (s, 1H), 9.4 (dd, 1H), 8.7 (s, 1H), 8.5 (d, 2H), 8.2 (d, 2H), 6.5 (d, 1H), 4.75 (m, 4H), 4.3 (m, 1H), 4.2 (m, 1H), 3.4 (m, 2H), 2.9 (s, 6H). MS(ESI+) m/z= 446.2 Example 28: Compound 28 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4-(N,N- dimethylsulfamoyl)phenyl)-1 l 4 -pyridine-3-carboxamide. Following General Procedure A: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-(N,N-dimethylsulfamoyl)phenyl)nicotinamide(0.55 g, 1.8 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq) in CH 3 CN (20 mL). After stirring for 2h at ambient temperature the solvent was evaporated and residue was taken up in anhydrous MeOH (20 mL) and cooled in an ice bath. SOCl 2 (3.5 eq.) was added dropwise and the solution was allowed to stand in the freezer at -5 o C for 72h. The solution was brought to room temperature and the product was precipitated with MTBE. The solvents were decanted from the product and the solids were dissolved in 5 mL of MeOH and allowed to stir at ambient temperature for 1h. A fine white precipitate formed which was filtered in a sintered glass funnel and washed with ice- cold MeOH (5 mL) followed by MTBE. The pure product (220 mg, 28%) was obtained as an off-white solid. 1 H NMR (D2O): d 9.68 (br s, 1H), 9.28 (d, 1H), 9.05 (d, 1H), 8.29 (t, 1H), 7.83 (m, 4H), 6.25, (d, 1H), 4.43-4.57 (m, 2H), 4.36 (t, 1H), 3.95 (ab q, 2H), 2.65 (s, 6H). MS(ESI+) m/z= 438.1 Example 29: Compound 29 Methyl 2-(4-(1-((2R,3R,4S,5R)-3,4-dihydroxy-(hydroxymethyl)tetrahyd rofuran-2-yl)-1l 4 - pyridine-3-carboxamido)phenyl)acetate. Following General Procedure B: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 2-(4-(nicotinamido)phenyl)acetate (0.50 g, 1.85 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq.) in DCM (20 mL). After stirring for 30 min HPLC analysis of an aliquot showed only about 20% conversion, so additional TMS-triflate (1.2 eq.) was added. The reaction mixture was stirred at ambient temperature for 1.5h and the solvent was evaporated and the residue was taken up in anhydrous MeOH (20 mL). SOCl 2 (3.5 eq.) was added dropwise to the solution at 0 o C and the reaction mixture was allowed to stir at 5 o C for 16h. HPLC analysis at that time showed about 25% of the mono and diacetate intermediates present so additional SOCl2(1 eq.) was added and stirring was continued for an additional 5h. Workup as described previously and purification on the ISCO in the usual fashion gave the product (340 mg, 46%). 1 H NMR (D2O): d 9.65 (s, 1H), 9.26 (d, 1H), 9.04 (d, 1H), 8.27 (t, 1H), 7.45 (d, 2H), 7.35 (d, 2H), 6.24 (d, 1H), 4.52 (app t, 1H), 4.46 (m, 1H), 4.35 (t, 1H), 3.94 (ab q, 2H), 3.74 (s, 2H), 3.68 (s, 3H). MS(ESI+) m/z = 403.2 Example 30: Compound 30 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofu ran-2-yl)-N-(4-(oxazol-5- yl)phenyl)-1l 4 -pyridine-3-carboxamide. Following General Procedure A: TMS-triflate (1.2 eq.) was added to a stirred mixture of N- (4-(oxazol-5-yl)phenyl)nicotinamide (1.1 g, 4.2 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq) in CH3CN (40 mL). After stirring for 2h at ambient temperature the solvent was evaporated and residue was taken up in anhydrous MeOH (20 mL) and cooled in an ice bath. After treatment with thionyl chloride (3.5 eq.) followed by stirring at 5 o C overnight, the product precipitated from solution. The solids were collected by filtration and washed 2 x 5 mL portions of ice-cold MeOH followed by a large volume of MTBE. The solids were dried under high vacuum for several hours to afford 0.54 g (32%) of product as a light yellow solid. 1 H NMR (DMSO-d 6 ): d 9.56 (s, 1H), 9.23 (d, 1H), 8.94 (d, 1H), 8.22 (m, 2H), 7.62 (q, 4H), 7.39 (s, 1H), 6.19 (d, 1H), 4.46 (m, 2H), 4.34 (t, 1H), 3.94 (ab q, 2H). MS(ESI+) m/z = 398.1 Example 31: Compound 31 Methyl 6-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydr ofuran-2-yl)-1l 4 - pyridine-3-carboxamido)nicotinate. Following General Procedure A: TMS-triflate (1.2 eq.) was added to a stirred mixture of methyl 6-(nicotinamido)nicotinate (0.50 g, 1.95 mmol) and 1,2,3,5-tetraacetyl- b-D- ribofuranose (1.1 eq) in dry CH3CN (20 mL). After stirring for 2h at ambient temperature the solvent was evaporated and residue was taken up in anhydrous MeOH (20 mL) and cooled in an ice bath. The mixture was treated with SOCl 2 (3.5 eq.) and stirred at 5 o C for 16h. HPLC at time still showed about 10% of a mixture of the mono and di-acetate intermediates so additional SOCl 2 (1 eq.) was added and stirring was continued for 5h. The product was precipitated by the addition of MTBE giving a white solid which was triturated with MTBE several times. The crude product was re-dissolved in 10 mL of dry MeOH and precipitated with MTBE as before. The product was filtered and washed with 2 x 5 mL portions of ice- cold MeOH followed by a large volume of MTBE. After drying under high vacuum for several hours, the product was obtained as a white solid (100 mg, 13%). 1 H NMR (D2O): d 9.72 (s, 1H), 9.28 (d, 1H), 9.08 (d, 1H), 8.93 (app d, 1H), 8.44 (dd, 1H), 8.32 (t, 1H), 8.10 (app d, 4H), 6.25 (d, 1H), 4.53 (t, 1H), 4.46 (m, 1H), 4.34 (t, 1H), 3.95 (ab q, 2H), 3.92 (s, 3H). MS(ESI+) m/z = 390.1 Example 32: Compound 32 Following General Procedure B: TMS-triflate (1.2 eq.) is added to a stirred mixture of the corresponding nicotinamido compound (1.6 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in CH3CN (15 mL). After stirring for 2h at ambient temperature, removal of the solvent and treatment with SOCl 2 (3.5 eq.) in MeOH, the solution is stirred for 16h at 5 o C. If HPLC shows 10% of the mono-acetate remaining, additional SOCl 2 (0.1 mL) is added and stirring is continued for 6h. The crude product is obtained after trituration with MTBE as a solid. Purification on the ISCO (12 g cartridge, elution with a gradient of 5% MeOH in DCM to 30% MeOH in DCM) furnishes the product as a solid. Example 33: Compound 33 Following General Procedure B: TMS-triflate (1.2 eq.) is added to a stirred mixture of the corresponding nicotinamido compound (1.6 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in CH3CN (15 mL). After stirring for 2h at ambient temperature, removal of the solvent and treatment with SOCl 2 (3.5 eq.) in MeOH, the solution is stirred for 16h at 5 o C. If HPLC shows 10% of the mono-acetate remaining, additional SOCl 2 (0.1 mL) is added and stirring is continued for 6h. The crude product is obtained after trituration with MTBE as a solid. Purification on the ISCO (12 g cartridge, elution with a gradient of 5% MeOH in DCM to 30% MeOH in DCM) furnishes the product as a solid. Example 34: Compound 34 Following General Procedure B: TMS-triflate (1.2 eq.) is added to a stirred mixture of the corresponding nicotinamido compound (1.6 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in CH3CN (15 mL). After stirring for 2h at ambient temperature, removal of the solvent and treatment with SOCl2 (3.5 eq.) in MeOH, the solution is stirred for 16h at 5 o C. If HPLC shows 10% of the mono-acetate remaining, additional SOCl 2 (0.1 mL) is added and stirring is continued for 6h. The crude product is obtained after trituration with MTBE as a solid. Purification on the ISCO (12 g cartridge, elution with a gradient of 5% MeOH in DCM to 30% MeOH in DCM) furnishes the product as a solid. Example 35: Compound 35 Following General Procedure B: TMS-triflate (1.2 eq.) is added to a stirred mixture of the corresponding nicotinamido compound (1.6 mmol) and 1,2,3,5-tetraacetyl- b-D-ribofuranose (1.1 eq.) in CH3CN (15 mL). After stirring for 2h at ambient temperature, removal of the solvent and treatment with SOCl2 (3.5 eq.) in MeOH, the solution is stirred for 16h at 5 o C. If HPLC shows 10% of the mono-acetate remaining, additional SOCl 2 (0.1 mL) is added and stirring is continued for 6h. The crude product is obtained after trituration with MTBE as a solid. Purification on the ISCO (12 g cartridge, elution with a gradient of 5% MeOH in DCM to 30% MeOH in DCM) furnishes the product as a solid. Example 36: Compound 36 A dry 100 mL flask is charged with 4.1 mmol of Compound 17. The flask is flushed with argon and 10 mL of trimethylphosphate is added. The resulting solution is cooled to 0 o C and treated with POCl3 (8.2 mmol, 2 eq.). The flask is sealed and allowed to stand in the freezer at -10 o C. After 2.5h the homogeneous solution is treated with triethylamine (2.0 mmol) over several minutes and allowed to stand in the freezer overnight. The reaction mixture is cooled in an ice bath and the well-stirred suspension is treated with water (82 mmol) over several minutes followed by solid NaHCO3 (28.7 mmol) and stirring is continued for 90 min. at 0 o C. The reaction mixture is treated with 100 mL of CH 3 CN containing 33 mmol of 90% formic acid to produce a solid. The solid is recovered by filtration, washed with CH3CN and placed under high vacuum to give a crude product. This material is purified by medium pressure chromatography on a column containing 50 g of aminopropyl functionalized silica. The product is dissolved in 25 mL of 60%/40% MeOH-CH3CN containing 100 mM formic acid and the column is equilibrated with the same solvent mixture. The product-containing fractions are combined and concentrated; co-evaporated from water (3 x 25 mL), frozen and lyophilized to give the product. Example 37: Compound 37 A dry 100 mL flask is charged with 4.1 mmol of Compound 13. The flask is flushed with argon and 10 mL of trimethylphosphate is added. The resulting solution is cooled to 0 o C and treated with POCl 3 (8.2 mmol, 2 eq.). The flask is sealed and allowed to stand in the freezer at -10 o C. After 2.5h the homogeneous solution is treated with triethylamine (2.0 mmol) over several minutes and allowed to stand in the freezer overnight. The reaction mixture is cooled in an ice bath and the well-stirred suspension is treated with water (82 mmol) over several minutes followed by solid NaHCO3 (28.7 mmol) and stirring is continued for 90 min. at 0 o C. The reaction mixture is treated with 100 mL of CH3CN containing 33 mmol of 90% formic acid to produce a solid. The solid is recovered by filtration, washed with CH 3 CN and placed under high vacuum to give a crude product. This material is purified by medium pressure chromatography on a column containing 50 g of aminopropyl functionalized silica. The product is dissolved in 25 mL of 60%/40% MeOH-CH 3 CN containing 100 mM formic acid and the column is equilibrated with the same solvent mixture. The product-containing fractions are combined and concentrated; co-evaporated from water (3 x 25 mL), frozen and lyophilized to give the product. Biological Assays Example B1: General Assay- 2 x 10 3 Hek293 (human embryonic kidney) and HepG2 (human hepatocellular carcinoma) cells plated per well in 96 well clear bottom black plate adhere O/N. The following day cells were treated with 2 mM NMN or 500 µM other compounds, and after 24 hours of treatment, cells were analyzed with CellTiter-Fluor and NAD assay. FIG. 1A and FIG. 1B depict NAD(H) in cells upon treatment with control or compounds according to Formula 1. FIG.1A is from Hek293 cells (human embryonic kidney cells), while FIG.1B is from HepG2 cells (human hepatocellular carcinoma cells). For both FIG. 1A and FIG. 1B, the Y-axis is the amount of NAD(H)/number of viable cells, normalized to 1.0 for no treatment; and the X-axis is as follows: 1: (control)- no treatment 2: (control)- treatment with nicotinamide mononucleotide (NMN) 3: (control)- treatment with PABA-methyl 4: Treatment with Compound 1 5: (control)- treatment with Compound A 6: Treatment with Compound 9 7: Treatment with Compound 7 8: Treatment with Compound 8 9: Treatment with Compound 6 10: Treatment with Compound 2 11: Treatment with Compound 4 12: Treatment with Compound 3 13: Treatment with Compound 5 Example B2: FIG. 2A, FIG. 2B, and FIG. 2C depict NAD(H) in normal cells upon treatment with control or Compound 1, according to Formula 2a. FIG.2A is from AML12 (2K/well) cells (murine normal hepatocytes), while FIG. 2B is from Hek293 cells (human embryonic kidney cells), and FIG.2C is from primary hPBMC cells (human peripheral blood mononuclear cells). For FIG.2A and FIG.2B, the Y-axis is the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment. For FIG. 2C, the Y-axis shows pg NAD(H)/micrograms total protein, normalized to 1.0 for no treatment. In FIG.2A, the X-axis is as follows: 1: (control)- no treatment 2: (control)- treatment with nicotinamide mononucleotide (NMN), 2 mM 3: (control)- treatment with nicotinamide mononucleotide (NMN), 0.5 mM 4: (control)- treatment with ethanol 5: Treatment with Compound 1, 0.5 mM 6: Treatment with Compound 1, 0.25 mM In FIG.2B, the X-axis is as follows: 1: (control)- no treatment 2: (control)- treatment with nicotinamide mononucleotide (NMN), 800 µM 3: (control)- no treatment (Prep 1) 4: Treatment with Compound 1, 800 µM (Prep 1) 5: (control)- no treatment (Prep 2) 6: Treatment with Compound 1, 800 µM (Prep 2) In FIG.2C, the X-axis is as follows: 1: (control)- no treatment 2: (control)- treatment with nicotinamide mononucleotide (NMN), 1 mM 3: Treatment with Compound 1, 1 mM Example B3: FIG.3A, FIG.3B, FIG.3C, and FIG.3D depict NAD(H) in cancer cells upon treatment with control or Compound 1, according to Formula 1. FIG.3A is from B16- F10 cells (murine melanoma), while FIG.3B is from RAW264.7 cells (murine tumor-derived macrophages), FIG.3C is from Jurkat cells (human acute T cell leukemia), and FIG.3D is from HepG2 cells (human hepatocellular carcinoma). For FIG.3B and FIG.3D, the Y-axis is the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment. For FIG. 3A and FIG. 3C, the Y-axis is pg NAD(H)/µg total protein, normalized to 1.0 for no treatment. In FIG.3A, the X-axis is as follows: 1: (control) no treatment 2: (control) NMN 1 mM 3: (control) NMN 250 µM 4: Compound 1, 250 µM 5: Compound 1, 500 µM 6: (control) PABA, 250 µM 7: (control) PABA, 500 µM 8: (control) PABA Methyl Ester, 250 µM 9: (control) PABA Methyl Ester, 500 µM In FIG.3B, the X-axis is as follows: 1: (control) no treatment 2: (control) NMN, 2 mM 3: (control) NMN, 500 µM 4: Compound 1, 500 µM 5: Compound 1, 250 µM In FIG.3C, the X-axis is as follows: 1: (control) no treatment 2: (control) NMN, 2 mM 3: (control) NMN, 1 mM 4: (control) NMN, 500 µM 5: (control) NMN, 250 µM 6: Compound 1, 500 µM 7: Compound 1, 250 µM In FIG.3D, the X-axis is as follows: 1: (control) no treatment 2: (control) NMN 800 µM 3: (control) no treatment (Prep 1) 4: Compound 1, 800 µM (Prep 1) 5: (control) no treatment (Prep 2) 6: Compound 1, 800 µM (Prep 2) Example B4: FIG.4A and FIG.4B depict NAD(H) level and viability in normal cells (Hek293 cells / human embryonic kidney cells) upon treatment with control or Compound 1, according to Formula 1, as a measure of cytotoxicity / cytostasis. In FIG. 4A, the Y-axis shows the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment, and the X-axis reflects the number of days of treatment. In FIG. 4B, the Y-axis shows the cell number as a measure of viability normalized to 1.0 for no treatment, and the X-axis reflects the number of days. Example B5: FIG.5A and FIG.5B depict NAD(H) level and viability in cancer cells (HepG2 cells / human hepatocellular carcinoma) upon treatment with control or Compound 1, according to Formula 1, as a measure of cytotoxicity / cytostasis. In FIG.5A, the Y-axis shows the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment, and the X-axis reflects the number of days of treatment. In FIG. 5B, the Y-axis shows the cell number as a measure of viability normalized to 1.0 for no treatment, and the X-axis reflects the number of days. For FIG.4A, FIG.4B, FIG.5A, and FIG.5B, the following legend applies: i. (Control) Untreated ii. (Control) Nicotinamide mononucleotide (NMN) iii. Compound 1 iv. Compound 1 + NMN v. (Control) FK866 vi. (Control) FK866 + NMN Example B6: General Assay for FIG. 6A and FIG. 6B: 2 x 103 Hek293 (human embryonic kidney) and HepG2 (human hepatocellular carcinoma) cells plated per well in 96 well clear bottom black plate adhere O/N. The following day, cells were treated with 2 mM NMN or 250 µM other compounds, after 24 hour of treatment cells analyzed with CellTiter- Fluor and NAD assay. FIG. 6A depicts NAD(H) level in normal cells (Hek293 cells / human embryonic kidney cells) upon treatment with control or various compounds. In FIG. 6A, the Y-axis shows the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment. FIG. 6B depicts NAD(H) level in cancer cells (HepG2 cells / human hepatocellular carcinoma) upon treatment with control or various compounds. In FIG.6B, the Y-axis shows the amount of NAD(H)/ number of viable cells, normalized to 1.0 for no treatment. In both FIG.6A and FIG.6B, the X-axis is as follows: 1: (control)- no treatment 2: (control)- treatment with nicotinamide mononucleotide (NMN) 3: (control)- treatment with PABA-nicotinamide (PABA nicotinate methyl ester) 4: (control)- treatment with DMSO vehicle 5: Treatment with Compound 1 6: Treatment with Compound 12 7: Treatment with Compound 13 8: Treatment with Compound 14 9: Treatment with Compound 15 10: Treatment with Compound 16 11: Treatment with Compound 17 12: Treatment with Compound 18 13: Treatment with Compound 19 14: Treatment with Compound 20 15: Treatment with Compound 21 16: Treatment with Compound 22 17: Treatment with Compound 23 18: Treatment with Compound 24