Substituted IP5 compounds for use in the treatment, inhibition of progression, and prevention of ectopic calcification

Abstract

The present invention refers to IP5 substituted compounds for use in the prevention, inhibition of progression, and treatment of (a) ectopic calcification and the consequences thereof, and (b) a disease and / or condition related to ectopic calcification and the consequences thereof. Also provided are methods, pharmaceutical compositions and formulations, methods of use, articles of manufacture, and kits for use in the prevention, inhibition of progression, and treatment of (a) ectopic calcification and the consequences thereof, and (b) a disease and / or condition related to ectopic calcification and the consequences thereof.

Description

[0001] IP5 Substituted Compounds for Use in the Treatment, Inhibition of Progression, and Prevention of Ectopic Calcification Technical field [1] The present invention is directed to IP5 substituted compounds for use in the treatment, inhibition of progression, and prevention of (a) ectopic calcification and (b) diseases and / or conditions related to ectopic calcification. Pharmaceutical and kits for such uses are also provided. State of the art [2] Ectopic calcification (EC) is a pathologic condition in which calcifications develop in soft tissues (Cotran R, et al., Pathological Basis of Disease, 5th Ed., Robbins S, et al., Eds. (WB Saunders, Philadelphia, PA, US, 1994, pp 1-35). The spectrum of EC disorders is broad, ranging from common vascular calcification associated with cardiovascular disease to rare hereditary calcification disorders affecting skin, eyes, brain parenchyma, kidneys, or cartilage (Giachelli C, Am J Pathol.1999; 154(3):671-67). The clinical presentation of EC depends on the localization of the calcific deposits (Snijders B, et al., J Clin Med.2023; 12(11):3687). [3] The causes of EC and its related diseases are diverse but can be grouped in 4 categories: (I) genetic mutations (e.g., GACI1, CALJA, PH, FOP, PXE), (ii) tissue repair response associated with inflammation and / or immunological responses (e.g., calcinosis cutis), (iii) metabolic calcium and phosphate balance disruption (e.g., renal disease), and (iv) idiopathic. Recent data suggest that numerous molecules may modulate this process. The discovery of biomarkers for identifying and / or characterizing these molecules is an expanding field of research (Mischke Y, et al., Am J Hum Genet.2012; 90(1):25-39). [4] Vascular calcification (VC) is the most therapeutically relevant EC disease or condition. VC may result in ischemic heart disease, hypertension, cardiac hypertrophy, or peripheral arterial disease (PAD) (Karwowski W, et al., Med. Sci. Monit. 2012; 18:RA1-RA11). Additionally, VC is a highly prevalent problem associated with aging, chronic kidney disease, and diabetes mellitus (Marulanda J, et al., Curr. Pharm. Des. 2014;20:5801-5810). In arteries, calcification is associated with CAD, atherosclerotic plaque burden, in peripheral vascular disease, and worse outcomes (e.g., increased risk of dissection) following angioplasty. In the heart, the valves are particularly prone to calcification. Degenerative calcific aortic stenosis is currently the most common valvular lesion encountered in clinical cardiology and one of the most difficult to manage. It is estimated that approximately 1–2% of the elderly population suffer from this pathology, which is characterized by encrustation of aortic valve leaflets with apatite mineral deposits and subsequent stiffening, tearing, and mechanical failure. Congenital anomalies, inflammatory changes such as those seen in rheumatic fever, renal disease, and age are all risk factors for aortic valve stenosis. [5] VC is also related to several rare disorders with life-threatening symptoms. For instance, in pseudoxanthoma elasticum (PXE), a systemic calcification disease, visual impairment or skin plaques can occur. In primary familial brain calcification (PFBC), another rare calcification disease in the basal ganglia, patients develop symptoms consisting of cognitive impairment, movement disorders, and neuropsychiatric problems. [6] Another important disease related to EC is peripheral artery disease (PAD). This disease is particularly pronounced in end stage kidney disease (PAD-ESKD) patients. It affects individuals with end stage kidney disease undergoing hemodialysis. PAD-ESKD causes a reduction in mobility, pain in the lower extremities, and can lead to critical limb ischemia, gangrene, and amputation. VC causes narrowing and stiffening of arteries which results in reduction of arterial blood flow and distal ischemia. Risk factors for PAD-ESKD include older age, diabetes, hypertension, and smoking (Chen J, et al., Nephrol Dial Transplant. 2016; 31(7):1145-1151). The duration of dialysis is an important risk factor for PAD-ESKD and the risk factors of hypertension and diabetes are more prevalent and more difficult to control in patients with ESKD than in the general population (Rajagopalan S et al., Circulation 2006; 114(18):1914-1922). Patients with ESKD have been excluded from prior clinical studies of medical therapies for PAD and thus there are no approved therapies specifically for patients with PAD-ESKD. [7] Currently, no causal treatment options exist which effectively halt or diminish EC. However, several pharmacological agents have been investigated that show promising results in slowing disease progression. Phosphate binders and calcimimetic agents such as cinacalcet, sodium thiosulfate, and vitamin K may decelerate vascular calcification (Singh A, et al., Mol. Biol. Rep.2021; 48:887-896). Therefore, there is a need in the art for new chemical entities that may be effective in treating, inhibiting the progression or preventing of diseases and conditions related to ectopic calcification. Summary of the invention [8] The present invention discloses a compound of general formula I: a pharmaceutically acceptable salt thereof, or a combination thereof, wherein (i) R1, R2, R3, R5, and R6 independently represent -OPO3H2 and R4 is a substituent group of formula II or formula III, or R1, R2, R3, R4, and R5 independently represent OPO3H2 and R6 is a substituent group of formula II or formula III, II III (ii) R1, R3, R4, R5, and R6 independently represent -OPO3H2 and R2 is a substituent group of formula II or formula III, (iii) R1, R2, R3, R4, and R6 independently represent -OPO3H2 and R5 is a substituent group of formula II or formula III, (iv) R2, R3, R4, R5, and R6 independently represent -OPO3H2 and R1 is a substituent group of formula II; or R1, R2, R4, R5, and R6independently represent -OPO3H2and R3is a substituent group of formula II or formula III, wherein, for formula II, n is an integer between 1 and 30, wherein the terminal group X is selected from the group consisting of -H, -OR, -NRR', -COOR, -CONRR', -NHCOR, - NHCOOR, -OCONR, -NHSO2R, -NHCONRR', halogen, -CF3, alkyl, alkenyl, alkynyl, carbocycle (saturated or unsaturated), and heterocycle (saturated or unsaturated), and wherein R and R' are H or an alkyl group, and wherein, for formula III, y and y’ are an integer between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the group consisting of alkyl, -COR, -OR, -NRR', -COOR, -CONRR', - NHCOR, -NHCOOR, -OCONR -NHSO2R, -NHCONRR', halogen, and -CF3, and wherein R and R' are H or an alkyl group for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof. [9] In some aspects, the compound of formula I is selected from the group consisting of Compounds 1 to Compound 53.

[0010] In some aspects, the pharmaceutically acceptable salt is a sodium or magnesium salt. In some aspects, the sodium salt is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt, decasodium salt or undecasodium salt.

[0011] The invention also provides a pharmaceutical composition comprising a compound of formula I disclosed above and at least one pharmaceutically acceptable excipient.

[0012] Also provided is a compound or pharmaceutical composition according to the invention for use in the treatment, inhibition of progression, and prevention of a disease and / or condition related to ectopic calcification or the consequences thereof in a subject in need thereof.

[0013] In some aspects, the subject is human. In some aspects, the administration is topical, enteral or parenteral. In some aspects, the parenteral administration is intravenous. In some aspects, the intravenous administration is by bolus injection or by infusion.

[0014] The present invention also provides a kit or article of manufacture comprising at least one compound of formula I or a pharmaceutical composition comprising a compound of formula I and instructions for administration according to any method disclosed herein. In some aspects, the kit or article of manufacture may also comprise at least one compound selected from the group consisting of the compounds listed in Table 1. Brief description of the drawings

[0015] Fig.1A and Fig.1B present representative structures of Compounds I_A: IP5-4 substituted compounds.

[0016] Fig. 2A and Fig. 2B present representative structures of Compounds I_B: IP5-2substituted compounds.

[0017] Fig. 3 presents representative structures of Compounds I_C: IP5-5 substituted compounds.

[0018] Fig. 4 presents representative structures of Compounds I_D: IP5-1 substituted compounds.

[0019] Fig.5 is a schematic representation of synthesis Scheme 1.

[0020] Fig.6 is a schematic representation of synthesis Scheme 2.

[0021] Fig. 7A and Fig. 7B are schematic representations of syntheses Scheme 3 and Scheme 6, respectively.

[0022] Fig. 8A and Fig. 8B are schematic representations of syntheses Scheme 4 and Scheme 7, respectively.

[0023] Fig. 9A and Fig. 9B are schematic representations of syntheses Scheme 5 and Scheme 8, respectively.

[0024] Fig. 10 shows Compound 47, Compound 48, and Compound 53 inhibition of calcification in hVSMC. Results represent mean ± SEM. (A) Statistical analysis: two- way ANOVA with two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli. Significant effects of the type of inhibitor and the concentration, as well as a significant interaction between them, were detected (p < 0.05). (B) The curve was fitted using a nonlinear regression model with variable slope (four parameters) (N=4).

[0025] Fig. 11 shows cultures of aortic valve interstitial cells (VIC) calcified valves donors) kept in basic growth media (control), osteodifferentiation media (Osteodiff) and osteodifferentiation media adding Compound 6 at various concentrations (1, 3, 10, 30, and 100 μM) for 3 weeks. Calcification was measured by Alizarin Red staining and quantified spectrophotometrically as relative calcification. Values are shown as dot plots with mean. For not normally distributed results a nonparametric one-way ANOVA (Kruskal–Wallis test) with Dunn's post-test was applied, p < 0.05 was considered statistically significant. Detailed description of the invention

[0026] The present invention provides IP5 substituted compounds of general formula I: a pharmaceutically acceptable salt thereof, or a combination thereof, wherein (i) R1, R2, R3, R5, and R6 independently represent -OPO3H2 and R4 is a substituent group of formula II or formula III, or R1, R2, R3, R4, and R5 independently represent - OPO3H2 and R6 is a substituent group of formula II or formula III, (See Fig.1A, 1B) II III (ii) R1, R3, R4, R5, and R6 independently represent -OPO3H2 and R2 is a substituent group of formula II or formula III, (See Fig.2A, 2B) (iii) R1, R2, R3, R4, and R6 independently represent -OPO3H2 and R5 is a substituent group of formula II or formula III, (See Fig.3) (iv) R2, R3, R4, R5, and R6 independently represent -OPO3H2 and R1 is a substituent group of formula II; or R1, R2, R4, R5, and R6 independently represent -OPO3H2 and R3 is a substituent group of formula II or formula III (See Fig.4), wherein, for formula II, n is an integer between 1 and 30, wherein the terminal group X is selected from the group consisting of -H, -OR, -NRR', -COOR, -CONRR', -NHCOR, - NHCOOR, -OCONR, -NHSO2R, -NHCONRR', halogen, -CF3, alkyl, alkenyl, alkynyl, carbocycle (saturated or unsaturated), and heterocycle (saturated or unsaturated), and wherein R and R' are H or an alkyl group, and wherein, for formula III, y and y’ are an integer between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the group consisting of alkyl, -COR, -OR, -NRR', -COOR, -CONRR', - NHCOR, -NHCOOR, -OCONR -NHSO2R, -NHCONRR', halogen, and -CF3, and wherein R and R' are H or an alkyl group, for use in the treatment, inhibition of progression, and prevention of ectopic calcification and the consequences thereof. In some aspects, the IP5 substituted compound is of formula IV, V, VI, VII, VII, VIII, IX, X or XI.

[0027] In some aspects, the IP5 substituted compound is a sodium or magnesium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt, decasodium salt or undecasodium salt.

[0028] Also provided are methods, pharmaceutical compositions and formulations, methods of use, articles of manufacture, and kits for the treatment, inhibition of progression, and treatment of ectopic calcification and the consequences thereof and disease and / or conditions related to ectopic calcification and the consequences thereof.

[0029] The present invention can be more readily understood if certain terms are first defined as in below. As used in this application, except as otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application. I. Definitions

[0030] The invention includes aspects in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes aspects in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[0031] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention is related. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2ndEd., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 3rdEd., 1999, Academic Press; and the Oxford Dictionary of Biochemistry and Molecular Biology, Revised, 2000, Oxford University Press, provide one of skill with a general dictionary of many of the terms used in this invention.

[0032] Units, prefixes, and symbols are denoted in their Système International d´Unités (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Where a range of values is recited, it is to be understood that each intervening integer value, and each fraction thereof, between the recited upper and lower limits of that range is also specifically disclosed, along with each subrange between such values. The upper and lower limits of any range can independently be included in or excluded from the range, and each range where either, neither or both limits are included is also encompassed within the invention.

[0033] Where a value is explicitly recited, it is to be understood that values which are about the same quantity or amount as the recited value are also within the scope of the invention. Where a combination is disclosed, each subcombination of the elements of that combination is also specifically disclosed and is within the scope of the invention. Conversely, where different elements or groups of elements are individually disclosed, combinations thereof are also disclosed. Where any element of an invention is disclosed as having a plurality of alternatives, examples of that invention in which each alternative is excluded singly or in any combination with the other alternatives are also hereby disclosed; more than one element of an invention can have such exclusions, and all combinations of elements having such exclusions are hereby disclosed.

[0034] About: The term "about" as used herein to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation per the practice in the art. Alternatively, "about" can mean a range of up to 20%. Furthermore, particularly with respect to biological systems or processes, the terms can mean up to an order of magnitude or up to 5-fold of a value.

[0035] When particular values or compositions are provided in the application and claims, unless otherwise stated, the meaning of "about" should be assumed to be within an acceptable error range for that particular value or composition. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. Thus, "about 10-20" means "about 10 to about 20." In general, the term "about" can modify a numerical value above and below the stated value by a variance of, e.g., 10 percent, up or down (higher or lower).

[0036] And / or: "And / or" where used herein is to be taken as specific invention of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0037] Angina pectoris: As used herein, the terms "angina pectoris" and "chronic stable angina" relate to chest pain or discomfort that occurs as the result of myocardial ischemia. It is a common presenting symptom among patients with coronary artery disease (CAD). Approximately 9.8 million Americans are estimated to experience angina annually, with 500,000 new cases of angina occurring every year.

[0038] Approximately: As used herein, the term "approximately," as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain aspects, the term "approximately" refers to a range of values that fall within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0039] Bolus administration: As used herein, the terms "bolus administration" and "bolus injection" refer a fast intravenous injection lasting less than 10 seconds, or an intravenous infusion lasting less than 3 minutes.

[0040] Calcific aortic valve stenosis: As used herein, the terms "calcific aortic valve stenosis", "CAVS", and "AVS" refer to one of the most prevalent heart valve disorders in developed countries characterized by progressive fibro-calcific remodeling and thickening of the aortic valve leaflets. Over the years, this disease evolves to cause severe obstruction to cardiac outflow. In developed countries, CAVS is the third-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension, with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old (Lindman B, et al., Nat Rev Dis Primers.2016; 2:16006).

[0041] Calciphylaxis: As used herein, the terms "calciphylaxis" and "CUA" refer to is a serious, uncommon disease in which calcium accumulates in small blood vessels of the fat and skin tissues. CUA causes blood clots, painful skin ulcers and may cause serious infections that can lead to death. CUA subjects usually suffer kidney failure and may require dialysis. The condition can also occur in people without kidney disease.

[0042] Cardiovascular disease in chronic kidney disease: As used herein, the terms "cardiovascular disease in CKD patients" refer to the higher risk of CKD patients of developing cardiovascular diseases such as e.g., coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Although the incidence and prevalence of cardiovascular events is already significantly higher in patients with early CKD stages (CKD stages 1-3) compared with the general population, patients with advanced CKD stages (CKD stages 4-5) exhibit a markedly elevated risk (Jankowski J, et al., Circulation 2021; 143(11):1157-1172).

[0043] Cardiovascular disease linked to aging: As used herein, the term "cardiovascular disease linked to aging" refers to the fact that adults over 65 years of age have a high risk of cardiovascular diseases such as heart failure, coronary artery diseases, hypertension, cerebrovascular disease, peripheral arterial disease, valvular disease, and cardiac arrhythmias. Aging is associated with changes in the heart and blood vessels that increase a person's risk of developing cardiovascular disease (North B, et al., Circ Res. 2012; 110(8):1097-1108). Age is an established independent risk factor for cardiovascular disease.

[0044] Comprising: It is understood that wherever aspects are described herein with the language "comprising" or "comprise" encompass otherwise analogous aspects described in terms of "consisting of" and / or "consisting essentially of".

[0045] Compound: As used herein, the term "compound," is meant to include any and all free bases, isomers, and isotopes of the structure depicted. As used herein, the term "isomer" means any geometric isomer, tautomer, zwitterion, stereoisomer, enantiomer, or diastereomer of a compound. Compounds can include one or more chiral centers and / or double bonds and can thus exist as stereoisomers, such as double-bond isomers (i.e., geometric E / Z isomers) or diastereomers (e.g., enantiomers (i.e., (+) or (-)) or cis / trans isomers). The present invention encompasses any and all isomers of the compounds described herein, including stereomerically pure forms (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures (e.g., racemates). Enantiomeric and stereomeric mixtures of compounds and means of resolving them into their component enantiomers or stereoisomers are well- known. A compound, salt, or complex of the present invention can be prepared in combination with solvent or water molecules to form solvates and hydrates by routine methods. In some aspects, the term compound is used to refer to an IP5 substituted compound of the present invention.

[0046] Consequences thereof: The phrase "consequences thereof" when referring to a disease or condition disclosed herein refers to symptoms, sequelae, complications, and combinations thereof associated with the disease or condition. As used herein, the term "symptom" refers to subjective or physical sign, indication, or evidence of disease or physical disturbance observed by the subject. In general, the term refers to any morbid phenomenon or departure from the normal in structure, function, or sensation, experienced by a subject and indicative of disease. Symptoms are felt or noticed by the individual experiencing the symptom but may not easily be noticed by others. In some aspects, a symptom can be a mild symptom, a moderate symptom, or severe symptom. As used herein, the term "mild symptom" refers to a symptom that is not life threatening and does not require hospitalization or intensive care treatment (e.g., at a hospital ICU). As used herein, the term "moderate symptom" refers to a symptom that may become life threatening and may require hospitalization. As used herein, the term "severe symptom" refers to a symptom that is life threatening and requires intensive care treatment (e.g., at a hospital ICU). As used herein, the term "complication" refers to a pathological process or event occurring during a disease or condition that is not an essential part of the disease or condition, where it may result from the disease / condition or from independent causes. Accordingly, the term complication refers to medical / clinical problems that are observed in subjects diagnosed with a disease or conditions disclosed herein. In some aspects, a complication can be temporary. In some aspects, a complication can be chronic or permanent. As used herein, the term "sequela" refers to a long term, chronic, or permanent complication.

[0047] Critical limb ischemia: As used herein, the terms "critical limb ischemia" and "CLI" refer to a severe obstruction of the arteries which markedly reduces blood flow to the extremities and progresses to the point of severe pain and even skin ulcers, sores, or gangrene. Critical limb ischemia is a very severe condition of peripheral artery disease.

[0048] Ectopic calcification: As used herein, the term "ectopic calcification" refers to an inappropriate biomineralization occurring in soft tissues. Ectopic calcifications are typically composed of calcium phosphate salts, including hydroxyapatite, but can also consist of calcium oxalates and octacalcium phosphate as seen in kidney stones.

[0049] Effective amount: As used herein, the term "effective amount" of a therapeutic agent, in reference to (i) an IP5 substituted compound of the present invention, (ii) any dosage form, pharmaceutical composition, or formulation disclosed herein comprising at least one IP5 substituted compound of the present invention, or (iii) a combination of an IP5 substituted compound of the present invention with one or more additional therapeutic agents), is that amount sufficient to effect beneficial or desired results. In some aspects, the beneficial or desired results are, for example, clinical results, and, as such, an "effective amount" depends upon the context in which it is being applied. The term "effective amount" can be used interchangeably with "effective dose," "therapeutically effective amount," or "therapeutically effective dose."

[0050] The term effective amount relates to the specific use of an IP5 substituted compound. For example, when an IP5 substituted compound is used for treating, inhibiting the progression, or preventing ectopic calcification, an effective amount would be an amount of the IP5 substituted compound capable of achieving the desired effect.

[0051] Enteral administration: As used herein, the term "enteral administration" and the related term "enterally" refer to any administration of an IP5 substituted compound of the present invention or a pharmaceutical composition comprising said compound via the gastrointestinal tract. Enteral administration includes, but is not limited to, the oral, sublingual, and rectal routes of administration.

[0052] General arterial calcification of infancy: As used herein, the terms "general arterial calcification of infancy" and "GACI" relates to a disorder affecting the circulatory system that becomes apparent before birth or within the first few months of life, and which is characterized by abnormal calcification of the arteries and thickening of the arterial walls. These changes lead to stenosis and stiffness of the arteries, resulting in heart failure in some affected individuals, with signs and symptoms including difficulty breathing, edema, cyanosis, hypertension, and cardiomegaly.

[0053] IP5 substituted compounds of the present invention: As used herein, the term "IP5 substituted compound of the present invention" and grammatical variants thereof refers to a compound of formula I wherein its substituents are those disclosed in compound Families I_A, I_B, I_C, and I_D described in detail below, and salts thereof (e.g., pharmaceutically acceptable salts thereof). In some aspects, the term IP5 substituted compound of the present invention encompasses Compounds 1 to 53, any salt thereof (e.g., a sodium salt), and any combination thereof. In some aspects, the term IP5 substituted compound of the present invention encompasses a compound of formula I which is an intermediate in the synthesis of Compounds 1 to 53, e.g., a compound selected from the group consisting of the compounds listed in Table 1, any salt thereof (e.g., a sodium salt), and any combination thereof. In some aspects, the term IP5 substituted compound of the present invention encompasses a compound of formula I which is Compound 1 to Compound 53 and a compound selected from the group consisting of the compounds listed in Table 1, any salt thereof (e.g., a sodium salt), and any combination thereof.

[0054] Group consisting of Compound 1 to Compound 53: In the context of the present invention, references to a "group consisting of Compound 1 to Compound 53", refers to a group of compounds that comprises Compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, and 53. In some aspects, the group consisting of Compound 1 to Compound 53 also comprises combinations thereof. In some aspects, a combination of compounds from the group consisting of Compound 1 to Compound 53 can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more compounds from the group consisting of Compound 1 to Compound 53.

[0055] Group consisting of the compounds listed in Table 1: In the context of the present invention, references to "Group consisting of the compounds listed in Table 1", refers to a group of intermediate compounds used, e.g., for the synthesis of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) i.e., Intermediates II_A, II_B, II_B’, II_C, and II_D, Intermediates III_A, III_B, III_C, and III_D, Intermediates IV_A, IV_B, IV_C, and IV_D, Intermediates V_A, V_B, V_C and V_D, Intermediates VI_A, Intermediates VII_A, Intermediates VIII_B and VIII_B’, Intermediates IX_D and Intermediates X_D. In some aspects, the group consisting of the compounds listed in Table 1 also comprises combinations thereof. In some aspects, a combination of compounds from the group consisting of the compounds listed in Table 1 can comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more compounds from the group consisting of the compounds listed in Table 1.

[0056] Kidney failure-related diseases: As used herein, the term "kidney failure-related diseases" refers to disease processes of a widely diverse nature in individuals with kidney damage and can refer, but is not limited, to any disease related to calcium or calcium metabolism disorders, such as adynamic bone, bone cancer, bone mineral disease, calcific tendinitis, calcinosis cutis, calciphylaxis, renal lithiasis, cardiovascular calcification, cardiovascular disease, osteomalacia, osteoporosis, podagra, and rheumatoid arthritis. Other kidney failure-related diseases may be of the cardiovascular type including, but not limited to, aneurysm, angina pectoris, arteriosclerosis, atherosclerosis, cardiac disease, cardiovascular disease linked to aging, cerebrovascular disease, coronary disease, heart failure, hypertension, myocardial infarction, peripheral vascular disease, and thrombosis. The patient with renal impairment may suffer concomitant cardiovascular accidents, events or diseases (e.g., ischemia, arrhythmia, myocardial infarction, stroke).

[0057] Non-bolus administration: As used herein, the terms "non-bolus type" and "non- bolus administration" refer to an intravenous injection lasting 10 or more seconds, or an intravenous infusion lasting 3 or more minutes.

[0058] Parenteral administration: As used herein, the term "parenteral administration" and the related term "parenterally" refer to the administration of an IP5 substituted compound of the present invention characterized by the physical breaching of a tissue of a subject and the administration of the compound through said breach in the tissue. Parenteral administration includes, but is not limited to, the administration of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) or a pharmaceutical composition comprising the compound, by the application of the compound or the composition through, for instance, a surgical incision or through a tissue-penetrating non-surgical wound. In particular, parenteral administration includes, but is not limited to, the epidural, intraarterial, intradermal, intrathecal, intramuscular, intraperitoneal, intrasternal injection, intravascular, intravenous, intravenous infusion, spinal, subcutaneous, and subcutaneous depot routes of administration.

[0059] Peripheral arterial disease: As used herein, the terms "peripheral arterial disease" and "PAD" refer to a narrowing and / or stiffening of the peripheral arteries to the legs (most commonly), stomach, arms, and head. Symptoms include intermittent claudication (leg pain when walking which resolves with rest), skin ulcers, bluish skin, cold skin, or poor nail and hair growth.

[0060] Prevention: As used herein, the terms "prevent", "preventing", and "prevention" refer to inhibiting the inception or decreasing the occurrence of a disease or condition in a subject (e.g., avert ectopic calcification or the consequence thereof in a subject.

[0061] Primary hyperoxaluria: As used herein, the terms "primary hyperoxaluria" or "PH" refer to a disorder of glyoxylate metabolism characterized by an excess of oxalate resulting in kidney stones, nephrocalcinosis and, ultimately, renal failure and systemic oxalosis. There are 3 types of PH. Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Primary hyperoxaluria type 2 (PH2), caused by mutations in the GRHPR gene, is an inherited disease in which the lack of a particular liver enzyme causes the body to accumulate excess amounts of oxalate. Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function.

[0062] Prophylaxis: As used herein, the term "prophylaxis" refers to a measure taken to maintain health and prevent or delay the onset of a disease or condition or to mitigate its extent and / or severity of the symptoms. Thus, a prophylactic use of a therapeutic agent disclosed herein, for example, (i) an IP5 substituted compound of the present invention, or (ii) a combination thereof, or (iii) any dosage form comprising at least one IP5 substituted compound of the present invention, or (iv) any formulation comprising at least one IP5 substituted compound of the present invention, or a (v) combination of an IP5 substituted compound of the present invention with one or more additional therapeutic agents, corresponds to that amount sufficient to effect beneficial or desired results.

[0063] Pseudogout: As used herein, the terms "pseudogout", also known as "calcium pyrophosphate dihydrate (CPPD) crystal deposition disease" or "pyrophosphate arthropathy" refer to a rheumatologic disorder believed to be caused by calcium pyrophosphate crystal accumulation in connective tissues, particularly joints such as the knee joint.

[0064] Pseudoxanthoma elasticum: As used herein, the terms "pseudoxanthoma elasticum" and "PXE" refer to a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. The lack of functional ABCC6 protein leads to ectopic calcification that is most apparent in the elastic tissues of the skin, eyes, and blood vessels. The clinical prevalence of PXE has been estimated at between 1 per 100,000 and 1 per 25,000, with slight female predominance.

[0065] Ranges: As described herein, any concentration range, percentage range, ratio range or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.

[0066] Subject: By "subject" or "individual" or "animal" or "patient" or "mammal," is meant any subject, particularly a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; bears, food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; rodents such as mice, rats, hamsters and guinea pigs; and so on. In certain aspects, the mammal is a human subject. In other aspects, a subject is a human patient. In a particular aspect, a subject is a human patient with ectopic calcification or at risk of having ectopic calcification.

[0067] Substantially: As used herein, the term "substantially" refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and / or proceed to completeness or achieve or avoid an absolute result. The term "substantially" is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.

[0068] Therapeutic agent: As used herein, the term "therapeutic agent" is used in a broad sense to include a composition comprising an IP5 substituted compound of the present invention that can provide a significant therapeutic benefit to a subject in need thereof. In some aspects, the subject in need thereof is a subject suffering or at risk of developing a disease or condition associated to ectopic calcification (e.g., CUA, PAD, PXE, CAVS). Thus, in general, a therapeutic agent according to the present invention can be an IP5 substituted compound of the present invention, alone or in combination with one or more additional therapeutic agents, that is administered in an amount sufficient to effect beneficial or desired results.

[0069] The term therapeutic agent also encompasses prophylactic, diagnostic or imaging agents comprising an IP5 substituted compound of the present invention, wherein the therapeutic agent is administered (i.e., topically, enterally or parenterally). Therapeutic agents of the present invention include agents that treat, inhibition the progression, or prevent ectopic calcification (e.g., CUA, PAD, PXE, CAVS) and / or can ameliorate and / or prevent any symptom associated with ectopic calcification.

[0070] Topical administration: As used herein, the term "topical administration" and the related term "topically" refer to any administration of an IP5 substituted compound of the present invention or a pharmaceutical composition comprising said compound by applying the compound or composition to a particular place on or in the body, such as the skin or a mucous membrane. Topical administration includes, but is not limited to, the aural, cutaneous, nasal, transdermal, vaginal, and urethral routes of administration.

[0071] Treating, treatment, therapy: As used herein, the terms "treating" or "treatment" or "therapy" refer to partially or completely alleviating, ameliorating, improving, relieving, delaying onset of, inhibiting progression of, reducing severity of, reducing incidence of one or more symptoms or features of disease, or any combination thereof. A treatment comprising an IP5 substituted compound of the present invention can be administered to a subject who does not exhibit signs of a disease, disorder, and / or condition, and / or to a subject who exhibits only early signs of a disease, disorder, and / or condition for the purpose of, e.g., (i) decreasing the risk of developing a pathology associated with the disease, disorder, and / or condition, (ii) delaying the onset of the disease, disorder, and / or condition, or a pathology associated with said disease, disorder, and / or condition, or (iii) mitigating the symptoms and / or sequels of the disease, disorder, and / or condition or a pathology associated with said disease, disorder, and / or condition.

[0072] Thus, in general, the term "treatment" refers to countering the effects caused as a result of the disease or pathological condition of interest in a subject including (i) inhibiting the disease or pathological condition, in other words, slowing or stopping the development or progression thereof; (ii) relieving the disease or pathological condition, in other words, causing said disease or pathological condition, or the symptoms thereof, to regress; (iii) stabilizing the disease or pathological condition, and (iv) any combination thereof.

[0073] ug, uM, uL: As used herein, the terms "ug," "uM," and "uL" are used interchangeably with "μg," "μΜ," and "μL" respectively. II. IP5 substituted compounds

[0074] The present invention provides IP5 substituted compounds, their methods of synthesis and their uses. In some aspects, the IP5 substituted compound is a compound of general formula I: a pharmaceutically acceptable salt thereof, or a combination thereof, wherein

[0075] R1, R2, R3, R5, and R6 independently represent -OPO3H2 and R4 is a substituent group of formula II or formula III, or R1, R2, R3, R4, and R5 independently represent - OPO3H2 and R6 is a substituent group of formula II or formula III, II III

[0076] R1, R3, R4, R5, and R6 independently represent -OPO3H2 and R2 is a substituent group of formula II or formula III,

[0077] R1, R2, R3, R4, and R6 independently represent -OPO3H2 and R5 is a substituent group of formula II or formula III,

[0078] R2, R3, R4, R5, and R6 independently represent -OPO3H2 and R1 is a substituent group of formula II; or R1, R2, R4, R5, and R6 independently represent -OPO3H2 and R3 is a substituent group of formula II or formula III,

[0079] wherein, for formula II, n is an integer between 1 and 30, wherein the terminal group X is selected from the group consisting of -H, -OR, -NRR', -COOR, -CONRR', - NHCOR, -NHCOOR, -OCONR, -NHSO2R, -NHCONRR', halogen, -CF3, alkyl, alkenyl, alkynyl, carbocycle (saturated or unsaturated), and heterocycle (saturated or unsaturated), and wherein R and R' are H or an alkyl group, and wherein, for formula III, y and y’ are an integer between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the group consisting of alkyl, -COR, -OR, -NRR', -COOR, -CONRR', - NHCOR, -NHCOOR, -OCONR -NHSO2R, -NHCONRR', halogen, and -CF3, and wherein R and R' are H or an alkyl group. In some aspects, the IP5 substituted compound is of formula IV, V, VI, VII, VII, VIII, IX, X or XI.

[0080] In some aspects, not all negative charges in an IP5 substituted compound of the present invention are compensated by charges in positively charged ions (e.g., Na+, Ca++, Mg++). Accordingly, an IP5 substituted compound of the present invention can be, for example, a tetraionic salt (e.g., tetrasodium salt), a pentaionic salt (e.g., pentasodium salt), a hexaionic salt (e.g., hexasodium salt), a heptaionic salt (e.g., heptasodium salt), an octaionic salt (e.g., octasodium salt), a nonaionic salt (e.g., nonasodium salt), a decaionic salt (e.g., decasodium salt) or a undecaionic salt (e.g., undecasodium salt). In some aspects, the presence of additional negatively charges group in a IP5 substituted compounds can lead to the formation of complexes with additional ions. In some aspects, the IP5 substituted compound of the present invention is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt, decasodium or undecasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. Formula I and the rest of formulas presented in the invention are meant to encompass any isomers of the compounds covered thereby.

[0081] The term "alkenyl" or "alkenyl chain" in the context of the present invention refers to a linear or branched alkyl chain (e.g., containing between 2 and 10 carbon atoms) containing one or more double bonds, either substituted or non-substituted. Examples include, among others, ethenyl, 1-propenyl, 2-propenyl, isopropenyl. 1-butenyl, 2- butenyl, 3-butenyl, and 1,3-butadienyl.

[0082] The term "alkyl" or "alkyl chain" in the context of the present invention refers to a hydrocarbon moiety, which can be saturated, partially unsaturated, linear, branched, cyclic or cyclic with linear or branched side chains containing from 1 to 30 carbon atoms. Examples include but are not limited are to C1-C4 alkyls such as methyl, ethyl, propyl, isopropyl, n- or isobutyl, and cycloalkyl such as cyclohexyl. The term alkyl can extend to alkyl groups linked or bridged by hetero atoms. Hetero atoms in the context of the present invention are nitrogen (N), sulfur (S), oxygen (O), and halogen.

[0083] The term "alkynyl" or "alkynyl chain" in the context of the present invention refers to a linear or branched alkyl chain (e.g., containing between 2 and 10 carbon atoms) containing one or more triple bonds, either substituted or non-substituted. Examples include, among others, ethynyl, propynyl, 1-butynyl, and 3-butynyl.

[0084] An "amine function" or "amine group" is a function NRR,’ with R and R’ selected independently, e.g., from hydrogen (-H) and an alkyl group such as an C1-Cn alkyl, wherein n is and integer between 0 and 30.

[0085] A "hydroxy function" or "hydroxy group" is OH.

[0086] A "carboxylic acid function" or "carboxylic acid group" is COOH or its anion, COO−.

[0087] A "carboxylic amide" is CONRR’ or NCOR, with R and R’ selected independently, e.g., from hydrogen (-H) and an alkyl group such as an C1-Cn alkyl, wherein n is and integer between 0 and 20.

[0088] A "carbocycle" refers to a three- to 10-membered carbocyclic ring that can be saturated, partially unsaturated or aromatic (e.g., phenyl, cyclopentyl, cyclopropyl) and which is bound to the rest of the molecule via any available C atom.

[0089] A "heterocycle" refers to a three- to 10-membered cyclic ring containing at least one heteroatom selected from among N, O, and S, that can be saturated, partially unsaturated or aromatic (e.g., triazole, piperazine, pyrazole) and which is bound to the rest of the molecule via any available C atom or N atom. The term includes heterocycle rings substituted with one or more halogen atoms.

[0090] A "Cy" refers to a cyclic linker comprising a carbocycle or a heterocycle. Examples of carbocycles and heterocycles include, among others, 1,3-phenyl, 1,4-phenyl, naphthyl, thienyl, furyl, pyrrolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, 1,2,4-triazolyl, tetrazolyl, 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, piperazyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzimidazolyl, benzofuranyl, isobenzofuranyl, indolyl, isoindolyl, benzothiophenyl, benzothiazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, azetidinyl, and aziridinyl.

[0091] A "halogen" group refers to fluorine, chlorine, bromine or iodine.

[0092] The term "-OPO32-" in the context of the present invention refers also indistinctly to -OPO3H- and -OPO3H2.

[0093] In some aspects, the IP5 substituted compounds of the present invention or intermediate compounds disclosed herein can be detected and / or quantified using the methods disclosed in US9612250. See also, US8377909, US8778912 and US20070066574.

[0094] The IP5 substituted compounds of the present invention can be present in any form commonly used in pharmaceutical technology. Particular aspects include, but are not limited to, the sodium salt, magnesium salt, potassium salt, ammonium salt, free acid, or a mixture of the preceding forms. Other pharmaceutically acceptable salts are known to the skilled artisan and can be obtained by methods previously described (Haynes M, et al., J. Pharmaceutical Sci.2005; 94:2111-2120.

[0095] In some aspects, an IP5 substituted compound of the present invention comprises or consists of an IP5 substituted compound selected from the group consisting of Compounds 1 to 53 and combinations thereof. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 1. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 2. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 3. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 4. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 5. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 6. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 7. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 8. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 9. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 10. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 11. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 12. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 13. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 14. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 15. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 16. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 17. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 18. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 19. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 20. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 21. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 22. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 23. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 24. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 25. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 26. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 27. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 28. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 29. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 30. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 31. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 32. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 33. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 34. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 35. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 36. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 37. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 38. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 39. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 40. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 41. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 42. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 43. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 44. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 45. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 46. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 47. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 48. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 49. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 50. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 51. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 52. In some aspects, an IP5 substituted compound of the present invention comprises or consists of Compound 53.

[0096] The IP5 substituted compounds of the present invention are disclosed in myo form.

[0097] The present invention also provides chemical intermediate compounds useful in the preparations of IP5 substituted compound of the present invention (e.g., Compound 1 to Compound 53). In some aspects, such intermediates are the compounds listed in Table 1. An intermediate compound disclosed herein can be converted to an IP5 substituted compound of the present invention by utilizing the procedures described herein. Thus, the present invention provides methods to produce an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compounds 1 to 53) comprising utilizing an intermediate compound selected from the group consisting of the compounds listed in Table 1. The present invention also provides methods of producing the intermediate compounds disclosed herein. Accordingly, the present invention provides methods of producing intermediates compounds selected from the group consisting of the compounds listed in Table 1 for producing IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compounds 1 to 53).

[0098] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula: IV wherein n is an integer between 1 and 30, alkyl is CH2 and X is -H, -OH, -OMe, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO2R, -NHCONRR', -CF3, alkyl, cyclopropane, cyclopentane or pyrazole. See Fig. 1A. In some aspects, n is an integer between 1 and 20. In some aspects, n is an integer between 1 and 10. In some aspects, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 5, alkyl is CH2and X is -H (Compound 1). In some aspects, n is 3, alkyl is CH2 and X is -H (Compound 24). In some aspects, n is 1, alkyl is CH2 and X is -H (Compound 22). In some aspects, n is 5, alkyl is CH2 and X is -OH (Compound 2). In some aspects, n is 10, alkyl is CH2 and X is -OH (Compound 21). In some aspects, n is 5, alkyl is CH2 and X is -OMe (Compound 3). In some aspects, n is 7, alkyl is CH2 and X is -OMe (Compound 23). In some aspects, n is 5, alkyl is CH2 and X is -COOH (Compound 4). In some aspects, n is 10, alkyl is CH2 and X is - COOH (Compound 20). In some aspects, n is 3, alkyl is CH2 and X is - CH(CH3)2 (Compound 12). In some aspects, n is 5, alkyl is CH2 and X is -CF3 (Compound 13). In some aspects, n is 5, alkyl is CH2 and X is -NHCOMe (Compound 19). In some aspects, n is 2, alkyl is CH2 and X is cyclopentane (Compound 16). In some aspects, n is 2, alkyl is CH2 and X is cyclopropane (Compound 17). In some aspects, n is 5, alkyl is CH2 and X is pyrazole (Compound 18). In some aspects, n is 5, alkyl is CH2 and X is - CONH2 (Compound 33).

[0099] In some aspects, n is an integer between 3 and 30, alkyl is CH2 and X is an amine group. See Fig.1A; Wang, 2014, supra. In some aspects, n is an integer between 3 and 20. In some aspects, n is an integer between 3 and 10. In some aspects, n is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, alkyl is CH2 and X is -NH2 (Compound 27). In some aspects, n is 6, alkyl is CH2 and X is -NH2 (Compound 28). In some aspects, n is an integer between 1 and 30, or between 1 and 2, when the compound is used for treating, inhibiting the progression or preventing ectopic calcification.

[0100] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula: V

[0101] wherein n is an integer between 1 and 30, alkyl is CH2 and X is -H, -OH, -OMe, amine group, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, - NHSO2R, -NHCONRR', -CF3, cyclopropane, cyclopentane, pyrazole or alkynyl group. See Fig.2A. In some aspects, n is an integer between 1 and 20. In some aspects, n is an integer between 1 and 10. In some aspects, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 5, alkyl is CH2 and X is -H (Compound 6). In some aspects, n is 3, alkyl is CH2 and X is -H (Compound 34). In some aspects, n is 5, alkyl is CH2and X is -OH (Compound 40). In some aspects, n is 5, alkyl is CH2and X is -OMe (Compound 7). In some aspects, n is 9, alkyl is CH2 and X is -OMe (Compound 8). In some aspects, n is 19, alkyl is CH2 and X is -OMe (Compound 9). In some aspects, n is 29, alkyl is CH2 and X is -OMe (Compound 10). In some aspects, n is 5, alkyl is CH2 and X is -NHCOMe (Compound 35). In some aspects, n is 5, alkyl is CH2 and X is -CF3 (Compound 36). In some aspects, n is 5, alkyl is CH2 and X is -CONH2 (Compound 37). In some aspects, n is 2, alkyl is CH2 and X is cyclopentane (Compound 38). In some aspects, n is 2, alkyl is CH2 and X is cyclopropane (Compound 39). In some aspects, n is 1, alkyl is CH2 and X is C≡CH (Compound 43).

[0102] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula: VI

[0103] wherein n is an integer between 1 and 30, alkyl is CH2 and X is -H, -OH, -OMe, amine group, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, - NHSO2R, -NHCONRR', -CF3, cyclopropane, cyclopentane or pyrazole. See Fig.3A. In some aspects, n is an integer between 1 and 20. In some aspects, n is an integer between 1 and 10. In some aspects, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, alkyl is CH2and X is -H (Compound 29). In some aspects, n is 9, alkyl is CH2 and X is -OMe (Compound 31). In some aspects, n is 5, alkyl is CH2 and X is -OMe (Compound 44). In some aspects, n is 5, alkyl is CH2 and X is -CF3 (Compound 45). In some aspects, n is 2, alkyl is CH2 and X is cyclopropane (Compound 30).

[0104] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula: VII

[0105] wherein n is an integer between 1 and 30, alkyl is CH2 and X is -H, -OH, -OMe, amine group, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, - NHSO2R, -NHCONRR', -CF3, cyclopropane, cyclopentane or pyrazole. See Fig. 4. In some aspects, n is an integer between 1 and 20. In some aspects, n is an integer between 1 and 10. In some aspects, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, alkyl is CH2 and X is -H (Compound 32). In some aspects, n is 9, alkyl is CH2 and X is -OMe (Compound 47). In some aspects, n is 5, alkyl is CH2 and X is -NHCOMe (Compound 49). In some aspects, n is 5, alkyl is CH2and X is -CF3(Compound 50). In some aspects, n is 2, alkyl is CH2 and X is cyclopropane (Compound 48). In some aspects, n is 2, alkyl is CH2 and X is cyclopentane (Compound 51).

[0106] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula:

[0107] wherein y and y' is an integer between 0 and 10, alkyl is CH2, Cy is selected from the group consisting of 1,3-substituted phenyl, 1,4-substituted phenyl, piperazine, triazole-1, and triazole-2, and Z is selected from the group consisting of -CH3, -OMe, - CF3, COCH3, and -COOH3. See Fig.1B. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound an octasodium salt or nonasodium salt. In some aspects, y or y' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some aspects, y is 3, y' is 0, alkyl is CH2, Cy is 1,4-substituted phenyl, and Z is -CH3 (Compound 11). In some aspects, y is 3, y' is 0, alkyl is CH2, Cy is 1,4-substituted phenyl, and Z is - OMe (Compound 14). In some aspects, y is 3, y' is 0, alkyl is CH2, Cy is 1,3-substituted phenyl, and Z is -CF3 (Compound 15). In some aspects, y is 2, y' is 0, alkyl is CH2, Cy is piperazine, and Z is -COCH3 (Compound 5). In some aspects, y is 3, y' is 2, alkyl is CH2, Cy is triazole-1, and Z is -COOH (Compound 25). In some aspects, y is 6, y' is 0, alkyl is CH2, Cy is triazole-1, and Z is -COOH (Compound 26).

[0108] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula:

[0109] wherein y and y' is an integer between 0 and 10, alkyl is CH2, Cy is selected from the group consisting of 1,3-substituted phenyl, 1,4-substituted phenyl, piperazine, triazole-1, and triazole-2, and Z is selected from the group consisting of -CH3, -OMe, - CF3, COCH3, and -COOH3. See Fig.2B. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound an octasodium salt or nonasodium salt. In some aspects, y or y' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some aspects, y is 5, y' is 1, alkyl is CH2, Cy is triazole-1, and Z is -OMe (Compound 41). In some aspects, y is 1, y' is 2, alkyl is CH2, Cy is triazole-2, and Z is -COOH (Compound 46).

[0110] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula:

[0111] wherein y and y' is an integer between 0 and 10, alkyl is CH2, Cy is selected from the group consisting of 1,3-substituted phenyl, 1,4-substituted phenyl, piperazine, triazole-1, and triazole-2, and Z is selected from the group consisting of -CH3, -OMe, - CF3, COCH3, and -COOH3. See Fig.3. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound an octasodium salt or nonasodium salt. In some aspects, y or y' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some aspects, y is 5, y' is 1, alkyl is CH2, Cy is triazole-1, and Z is -OMe (Compound 42).

[0112] In some aspects, an IP5 substituted compound of the present invention comprises or consists of a compound of the following formula:

[0113] wherein y and y' is an integer between 0 and 10, alkyl is CH2, Cy is selected from the group consisting of 1,3-substituted phenyl, 1,4-substituted phenyl, piperazine, triazole-1, and triazole-2, and Z is selected from the group consisting of -CH3, -OMe, - CF3, COCH3, and -COOH3. See Fig.4. In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, pentasodium salt, hexasodium salt, heptasodium salt or octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, octasodium salt, nonasodium salt or decasodium salt. In some aspects, the IP5 substituted compound an octasodium salt or nonasodium salt. In some aspects, y or y' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. In some aspects, y is 5, y' is 1, alkyl is CH2, Cy is triazole-1, and Z is -OMe (Compound 52). In some aspects, y is 1, y' is 2, alkyl is CH2, Cy is triazole-2, and Z is -COOH (Compound 53). Table 1 Intermediates _ _ _ _

[0114] IP5 substituted compounds of the present invention and intermediates for their synthesis can be synthesized by using the methods described herein, as well as other processes known in the field of the organic chemistry. In some aspects, the methods include, but are not limited to, the general procedures shown in the synthesis Schemes 1, 2, 3, 4, 5, 6, 7 and 8 described herein. Thus, in some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 1 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 2 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 3 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 4 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 5 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 6 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 7 disclosed below. In some aspects, the present invention provides a method to manufacture an IP5 substituted compound of the present invention comprising applying synthetic Scheme 8 disclosed below.

[0115] In some aspects, the present invention provides a method to manufacture an intermediate for the synthesis of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) comprising applying any of synthetic Scheme 1, Scheme 2, Scheme 3, Scheme 4, Scheme, 5, Scheme 6, Scheme 7 or Scheme 8 disclosed below as applicable.

[0116] Scheme 1: In general, the IP5 substituted compounds of the present invention (i.e., Compounds I_A) can be obtained by deprotecting the intermediates of formula IV_A (Scheme 1). The "protective group" or GP, can be, without limitation, benzyl, levulinylbenzyl, tert-butyl, o,o’-xylenyl (by union of 2 PG in the same phosphate), 9- fluorenylmethyl, cyanoethyl and other suitable protective groups in each case. Intermediates of formula IV_A may be achieved by phosphorylation of an intermediate of formula III_A according to procedures described in the literature such as reaction with a phosphoroamidite derivative and subsequent oxidation. At the same time, intermediates of formula III_A can be obtained by hydrolysis in acid media of intermediates of formula II_A. Finally, intermediates of formula II_A may be obtained by alkylation of intermediate (2) with an alkylating agent. Preparation of (2) was previously described in the literature (Martin S, et al., J Org Chem 1994; 59(17): 4805-4820, Kardivel M, Org Biomol Chem 2008; 6(11):1966-1972). The "leaving Group" or LG, may be, without limitation, chloride, bromide, iodide, toluenesulfonyl (Ts) or methylsulfonyl (Ms). See Fig.5.

[0117] Scheme 2: As an alternative to Scheme 1, when R4 or R6 contain a substituted 1,2,3-triazole, compounds of formula I_A can be obtained by following the alternative route described in Scheme 2. In this way, intermediates of formula III_A can be obtained via a click reaction by using as starting materials an intermediate of formula VI_A and an alkynyl “click agent.” Intermediates VI_A can be achieved by alkylation and hydrolysis of intermediate 2 with an appropriate reagent. As another alternative, when R4 or R6 contain a terminal amine group, compounds of formula I_A can be obtained by phosphorylation of compound VI_A in order to obtain compounds VII-A, and by the subsequent deprotection / reduction of such compounds. See Fig.6.

[0118] Scheme 3: Compounds I_B may be obtained using a similar synthetic route used for compounds I_A. Thus, compounds I_B may be obtained by deprotecting intermediates of formula IV_B (Scheme 3). Intermediates of formula IV_B may be attained by phosphorylating an intermediate of formula III_B. At the same time, intermediates of formula III_B can be obtained by the hydrolysis in acid media of intermediates of formula II_B or VIII_B. Intermediates of formula VIII_B, may be achieved by the debenzylation of intermediates II_B.’ Finally, intermediates of formula II_B or B’ may be obtained by the alkylation of intermediates (3) or (4), respectively, with an alkylating agent. Preparations (3) and (4) have been described previously in the art (Aiba T, et al., Org Biomol Chem 2016; 14(28):6672-6675 and Chen W, et al., Eur J Med Chem 2015; 93:172-181). As an alternative, when R2 contain a substituted 1,2,3- triazole, compounds of formula I_B can be obtained by following an alternative route. In this way, intermediates of formula III_B can be also obtained via a click reaction by using as starting materials alkynyl intermediate of formula III_B and an azide “click agent.” See Fig.7A.

[0119] Scheme 4: Compounds I_C can be obtained by the deprotection of intermediates of formula IV_C (Scheme 4). Intermediates of formula IV_C may be achieved by phosphorylating intermediates of formula III_C. Intermediates of formula III_C can be obtained by the debenzylation of intermediates II_C. Finally, intermediates of formula II_C may be obtained by the alkylation of intermediate (33) with an appropriate alkylating agent. Preparation of (33) has been previously described in the art (Phenix C. et al., ChemBioChem 2008; 9(10):1591-1602). See Fig.8A.

[0120] Scheme 5: Compounds I_D may be obtained by the deprotection of intermediates of formula IV_D (Scheme 5). Intermediates of formula IV_D may be achieved by phosphorylating intermediates of formula III_D. Intermediates of formula III_D can be obtained by the debenzylation of intermediates IX_D. Intermediates IX-D can be obtained by the hydrolysis of intermediates II_D. Finally, intermediates of formula II_D may be obtained by the alkylation of intermediate (34) with an appropriate alkylating agent. Preparation of racemate (34) has been in the art (Chen, 2015, supra). As an alternative, when R2 contain a substituted 1,2,3-triazole, compounds of formula I_D can be obtained by following the alternative route. In this way, intermediates of formula IX_D can be also obtained via a click reaction by using as starting materials alkynyl intermediate of formula IX_D and an azide “click agent.” See Fig.9A.

[0121] Scheme 6: As an alternative to Scheme 3, when R2 contain a substituted 1,2,3- triazole or an acylamine, compounds of formula I_B can be obtained by following the alternative route described in Scheme 6. In this way, intermediates of formula III_B can be also obtained via a click reaction by using as starting materials an azide intermediate of formula V_B and an alkynyl “click agent.” Intermediate V_B can be achieved by alkylation of intermediate 3 with an appropriate reagent. As another alternative, when R2 contains a terminal acylamine group, compounds of formula III_B can be obtained by amidation of the corresponding amino compound See Fig.7B.

[0122] Scheme 7: As an alternative to Scheme 4, when R5 contain a substituted 1,2,3- triazole, compounds of formula I_C can be obtained by following the alternative route described in Scheme 7. In this way, intermediates of formula II_C can be also obtained via a click reaction by using as starting materials an azide intermediate of formula V_C and an alkynyl “click agent.” Intermediate V_C can be achieved by alkylation of intermediate 33 with an appropriate reagent. See Fig.8B.

[0123] Scheme 8: As an alternative to Scheme 5, when R1 or R3 contain a substituted 1,2,3-triazole, compounds of formula I_D can be obtained by following the alternative route described in Scheme 8. In this way, intermediates of formula IX_D can be also obtained via a click reaction by using as starting materials an alkinyl intermediate (where X is a triple bond) of formula V_C and an azide “click agent.” Intermediate V_C (where X is a triple bond) can be achieved by alkylation of intermediate 34 and subsequent hydrolysis of such alkenyl-protected compound II_D. As another alternative, When R1 or R3 contain an alkyl group, intermediates of formula with an alkyl as R1, can be obtained via debenzilation of intermediate IX_D where X correspond to a triple bond. See Fig.9A.

[0124] Representative IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) are presented herein and all of them are in the myo conformation. However, it is to be understood that any exemplary IP5 substituted compound of the present invention in the myo conformation is not limited to the representative conformation displayed. Thus, for example, Compounds 1 to 53 and the intermediates presented herein are in the myo conformation. In this conformation, the natural myo isomer has a structure in which five of the six hydroxyls (the first, third, fourth, fifth, and sixth) are equatorial, whereas the second hydroxyl group is axial.

[0125] The present invention also provides methods to manufacture a medicament for the treatment of ectopic calcification comprising using an intermediate compound selected from the group consisting of the compounds listed in Table 1. Also provided is a compound of formula I (e.g., selected from the group consisting of Compound 1 to Compound 53) for use as a medicament. Also provided is the use of a compound of formula I (e.g., selected from the group consisting of Compound 1 to Compound 53) for the manufacture of a medicament for the prevention or treatment of a disease related to ectopic calcification. III. Pharmaceutical compositions

[0126] The present invention also provides pharmaceutical compositions for use in the treatment, inhibition of progression, and prevention of (a) ectopic calcification or the consequences thereof and (b) a disease and / or condition related to ectopic calcification and the consequences thereof in a subject in need thereof, wherein the pharmaceutical composition comprises at least one IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53). In some aspects, the pharmaceutical composition comprises an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) alone or together with one or more pharmaceutically acceptable excipients or carriers.

[0127] The term "excipient" as used herein refers to a substance which helps absorption of the elements of the pharmaceutical composition, stabilizes said elements, activates or helps preparation of the composition. Thus, examples of excipients used in parenteral formulations include, but are not limited to, antimicrobial agents (e.g., benzalkonium chloride, metacresol, thimerosal), co-solvents (e.g., ethanol), buffers, tonicity agents (e.g., NaCl) and pH adjusting factors (e.g., carbonate, citrate, phosphate solutions).

[0128] As is the case for the excipient, the "pharmaceutically acceptable vehicle" is a substance used in the composition to dilute any of the components contained therein to a determined volume or weight (e.g., a 0.9% (w / v) NaCl aqueous solution). The pharmaceutically acceptable vehicle is an inert substance or a substance with an analogous action to any of the elements comprising the pharmaceutical composition of the present invention. The role of said vehicle is to allow the incorporation of other elements, allow better dosing and administration or to provide consistency and shape to the composition.

[0129] Pharmaceutical compositions can comprise from approximately 1% to approximately 95% active ingredient. In some aspects, e.g., the pharmaceutical compositions of the present invention can comprise from approximately 20% to approximately 90% active ingredient (i.e., an IP5 substituted compound of the present invention or a combination thereof, alone or in combination, e.g., with one or more additional therapeutic agents).

[0130] Formulations of a pharmaceutical composition suitable for parenteral administration comprise the active ingredient, e.g., an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53), combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline (e.g., a 0.9% (w / v) NaCl aqueous solution). Such formulations can be prepared, packaged, or sold in a form suitable for bolus administration or for non-bolus administration. Injectable formulations can be prepared, packaged, or sold in unit dosage form, such as in ampules or in multi-dose containers containing a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and implantable sustained-release or biodegradable formulations. Such formulations can further comprise one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents.

[0131] In some aspects, in a formulation for parenteral administration, the active ingredient, e.g., an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53), is provided in dry (i.e., powder or granular) form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition.

[0132] The pharmaceutical compositions can be prepared, packaged, or sold in the form of a sterile injectable aqueous or oily suspension or solution. This suspension or solution can be formulated according to the known art, and may comprise, in addition to the active ingredient (e.g., an inositol phosphate of the present invention), additional ingredients such as the dispersing agents, wetting agents, or suspending agents described herein. Such sterile injectable formulations can be prepared using a non-toxic parenterally acceptable diluent or solvent, such as water or 1,3-butanediol, for example. Other acceptable diluents and solvents include, but are not limited to, Ringer's solution, isotonic sodium chloride solution, and fixed oils such as synthetic mono- or di-glycerides.

[0133] Other administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form, in a liposomal preparation, or as a component of a biodegradable polymer system. Compositions for sustained release or implantation can comprise pharmaceutically acceptable polymeric or hydrophobic materials such as an emulsion, an ion exchange resin, a sparingly soluble polymer, or a sparingly soluble salt. Compositions and methods of making formulations for administering the IP5 substituted compounds of the present invention, including controlled- or sustained-release formulations containing the said active agents, are described in the art. See, e.g., Remington: The Science and Practice of Pharmacy, 23rdEd., 2021, Academic Press; US6340475, US6488962, US6451808, US5972389, US5582837, and US5007790; US20030147952, US20030104062, US20030104053, US20030044466, US20030039688, and US20020051820; WO2003035041, WO2003035040, WO2003035029, WO2003035177, WO2003035039, WO2002096404, WO2002032416, WO2001097783, WO2001056544, WO2001032217, WO1998055107, WO1998011879, WO1997047285, WO1993018755, and WO1990011757.

[0134] Medicaments according to the invention are manufactured by methods known in the art, especially by conventional mixing, coating, granulating, dissolving or lyophilizing.

[0135] The present invention also provides a compound or a combination of compounds or pharmaceutical formulation according to any of the above aspects of the invention, in the broadest definition given, or as specified in any of the aspects presented above, for use as a medicament.

[0136] The present invention also provides a compound or combination of compounds or pharmaceutical formulation according to any of the above aspects of the invention, in the broadest definition given, or as specified in any of the aspects presented above, for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof and (b) a disease and / or condition related to ectopic calcification and the consequences thereof in a subject in need thereof.

[0137] The present invention also provides a compound or combination of compounds or pharmaceutical formulation according to any of the above aspects of the invention, in the broadest definition given, or as specified in any of the aspects presented above, for the manufacture of a medicament for use in the treatment, inhibition of progression, and prevention of (a) ectopic calcification or the consequences thereof and (b) a disease and / or condition related to ectopic calcification and the consequences thereof in a subject in need thereof. IV. Articles of manufacture and kits

[0138] The present invention also provides articles of manufacture and kits. Such articles of manufacture and kits can comprise a container (e.g., a box) comprising one or more vials containing a formulation comprising one or more of the IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) and / or solvents for their medical administration or other uses according to the methods disclosed herein.

[0139] A kit or article of manufacture provided according to this invention can also comprise brochures or instructions describing the process of medical administration and dosages disclosed herein, or the use of the IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) according to the methods disclosed herein. In some aspects, kit or article of manufacture can comprise multiple vials, each one of them containing a single dose. In other aspects, kit or article of manufacture can comprise one or more vials, each one of them comprising more than one dose.

[0140] In some aspects, the article of manufacture is a bag containing a solution of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53). In other aspects, the article of manufacture is a bottle (e.g., a glass bottle or a plastic bottle) containing a solution of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53). In some aspects, the article of manufacture is a bag containing an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) in powder form for reconstitution in an appropriate solvent. In other aspects, the article of manufacture is a bottle (e.g., a glass bottle or a plastic bottle) containing an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) in powder form for reconstitution in an appropriate solvent.

[0141] The kits and articles of manufacture can include instructions for conducting one or more administrations of the IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) according to the methods and dosages disclosed herein.

[0142] Instructions included in the kits and articles of manufacture can be affixed to packaging material or can be included as a package insert. While the instructions are typically written or printed materials, they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated. Such media include, but are not limited to, electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. As used herein, the term "instructions" can include the address of an internet site that provides the instructions. V. Uses of IP5 substituted compounds of formula I

[0143] In one aspect, the present invention refers to IP5 substituted compounds of general formula I (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof. In some aspects, the present invention relates to a method for the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof, which comprises administering a therapeutically effective amount of an IP5 substituted compound of the invention. In some aspects, the invention refers to the use of an IP5 substituted compound of the invention for the manufacture of a medicament for the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof. In some aspects, the IP5 substituted is a compound of general formulas IV to XI or any combination thereof. In some aspects, the IP5 substituted is Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof. In some aspects, a therapeutically effective amount of the IP5 substituted compound of the invention is administered to the subject in need thereof.

[0144] In some aspects, the IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) can be administered by the topical, enteral or parenteral route of administrations. In some aspects, the parenteral administration is via the intravenous, intraperitoneal, intramuscular, intraarterial or subcutaneous route of administration. In some aspects, the compound can be administered as a component of a hemodialysis, hemofiltration or peritoneal dialysis solution.

[0145] In some aspects, the IP5 substituted compounds of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) can be administered by any appropriate method, e.g., a method that provokes a non-bolus type release or effect, such as intravascular (e.g., intravenous) infusion, other parenteral (e.g., subcutaneous, subcutaneous depot, intraperitoneal, intramuscular, intradermal, intrathecal, epidural, spinal or others known to a person skilled in the art), topical (e.g., intranasal, inhalation, intravaginal, transdermal or others known to a person skilled in the art), enteral (e.g.. oral, sublingual, rectal.) administrations, oral, spinal, intraperitoneal preparations or others known to a person skilled in the art.

[0146] In the particular case of patients treated with dialysis, an appropriate method of administration consists of an administration (e.g., a non-bolus type) of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) via a dialysis apparatus (before or after the filter) instead of directly injecting the IP5 substituted compound of the present invention into the patient intravenously. Thus, blood can be treated with the IP5 substituted compound of the present invention as it leaves the patient and circulates through the dialysis circuit and, when the blood containing the IP5 substituted compound of the present invention returns to the body, the IP5 substituted compound has been introduced into the blood in a manner that presents a series of advantages. In the case of dialysis patients, administration of an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) via the dialysis apparatus allows the blood to equilibrate with the dialysis fluid prior to returning to the body.

[0147] In some aspects, an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) is administered intravenously via intravenous infusion. In another aspect, an IP5 substituted compound of the present invention is administered subcutaneously. In yet another aspect, an IP5 substituted compound of the present invention is administered topically. In some aspects, when an IP5 substituted compound of the present invention is administered to a patient undergoing dialysis such administration (e.g., intravenous administration via infusion) can occur during a dialysis treatment. In some aspects, the IP5 substituted compound of the present invention is administered before a dialysis treatment. In some aspects, the IP5 substituted compound of the present invention is administered after a dialysis treatment.

[0148] In some aspects, the present invention refers also to a pharmaceutical composition for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof comprising an IP5 substituted compound of the present invention or any combination thereof, and at least one pharmaceutically acceptable excipient. In some aspects, the IP5 substituted compound is of general formulas IV to XI or any combination thereof. In some aspects, the IP5 substituted is Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof. In some aspects, a therapeutically effective amount of the pharmaceutical composition of the invention is administered to the subject in need thereof.

[0149] The present invention also provides methods to manufacture a medicament for the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof which comprises using an intermediate compound selected from the group consisting of the compounds listed in Table 1.

[0150] Ectopic calcifications (e.g., cutaneous, subcutaneous calcifications) are related to the pathological crystallization of calcium and arise as complications in numerous diseases and conditions. Ectopic calcifications are often damaging in soft tissues such as aorta, brain, carotid, femoral, heart, heart valves, joints, kidney, and lungs. This is often taken for granted as an age-dependent process, but recent data suggest that a myriad of molecules might modulate this process in an active fashion (Nitschke Y, et al., Trends Cardiovasc Med. 2012; 22(6):145-149). The IP5 substituted compounds of the present invention are selective calcification inhibitors that work by binding to the growth sites of hydroxyapatite (HAP) crystals, thereby selectively inhibiting the final common step in the pathway of ectopic calcification, including vascular calcification. Since the IP5 substituted compounds of the present invention are effective in inhibiting vascular calcification in various types of soft tissue, they could be useful for treating diseases and / or conditions associated to the ectopic calcification of such specific types of soft tissue.

[0151] In one aspect, the present invention refers to an IP5 substituted compound or pharmaceutical composition of the invention for use in the treatment, inhibition of progression, and prevention of a disease and / or condition related to ectopic calcification or the consequences thereof in a subject in need thereof.

[0152] In some aspects, the disease and / or condition related to ectopic calcification or the consequences thereof according to the invention include, but are not limited to, adrenal and intracranial calcification in familial cerebral cavernous malformations, adynamic bone, age-related macular degeneration (AMD) related to calcium deposits, bone cancer, bone mineral disease, breast calcification, calcific band keratopathy, calcific tendinitis, calcification in osteoarthritis, calcification of articular cartilage in osteoarthritis, calcification of joints and arteries (CALJA), calcification of the seminal vesicles, calcinosis cutis, calciphylaxis (CUA), calcium pyrophosphate deposition disease (CPPD), cardiovascular diseases and / or associated conditions, chondrocalcinosis, colon cancer, diabetic kidney disease, dystrophic calcification, failure of renal transplant grafts, familial cerebral cavernous malformations (FCCM), fibrodysplasia ossificans progressiva (FOP), hyperostosis-hyperphosphatemia syndrome (HHS), hyperphosphatemic familial tumoral calcinosis (HFTC), idiopathic brain calcification (Fahr's disease), idiopathic mesenteric phlebosclerosis (IMP), kidney stones (i.e., renal lithiasis), metastatic calcification, nephrocalcinosis, neurocysticercosis-related calcification, osteomalacia, osteoporosis, pineal calcification, phlebosclerotic colitis, podagra, primary familial brain calcification (PFBC), primary hyperoxaluria (PH), pseudoxantoma elasticum (PXE), rheumatoid arthritis, sialolithiasis, Sjorgen's syndrome parotid glands calcification, seminal vesicle calculi, skin cancer, soft tissue calcification owing to sarcoidosis, Wolman's disease adrenal calcification, and wound healing related to diabetic ulcers.

[0153] In some aspects, the cardiovascular diseases and / or associated conditions related to ectopic calcification or the consequences thereof according to the invention include, but are not limited to acute ischemic stroke (ACS), aneurysm, angina pectoris (chronic stable angina), aortic artery calcification, aortic calcification, aortic stenosis, aortic valve calcification, arrhythmia, arteriosclerosis, arterial stiffness, arteriovenous fistula (AVF) failure, atherosclerosis, calcific aortic valve stenosis (CAVS or AVS), cardiac death, cardiac disease, cardiovascular calcification, cardiovascular disease in chronic kidney disease (CKD) patients, cardiovascular disease linked to aging, cardiovascular mortality, cerebrovascular disease, congestive heart failure, coral reef aorta (CRA), coronary artery calcification, coronary artery disease, coronary disease, critical limb ischemia (CLI), electrocardiographic abnormalities, general arterial calcification of infancy (GACI), heart failure, hypertension, ischemia, left ventricular hypertrophy, major adverse cardiovascular events (MACE) in hemodialysis (HD) patients, Mönckeberg's medial sclerosis (MMS), myocardial calcification, myocardial infarction, myocardial ischemia, pericardial calcification, peripheral arterial disease (PAD), peripheral vascular disease (PVD), porcelain aorta and calcification of anastomosis site after coronary artery bypass grafting (CABG), portal vein calcification, stroke, thrombosis, valvular calcification, and vascular calcification.

[0154] In some aspects, the present invention refers to IP5 substituted compounds of general formula I (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) or the pharmaceutical compositions of the invention for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof, wherein the ectopic calcification occurs or may occur in aorta, brain, carotid, femoral, heart, heart valve, joint, kidney or lung tissue or any combination thereof. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in aorta tissue include, but are not limited to, aortic artery calcification, aortic calcification, aortic stenosis, aortic valve calcification, arteriosclerosis, arterial stiffness, atherosclerosis, calcific aortic valve stenosis (CAVS or AVS), cardiovascular disease linked to aging, cardiovascular mortality, coral reef aorta (CRA), electrocardiographic abnormalities, general arterial calcification of infancy (GACI), heart failure, peripheral arterial disease (PAD), and peripheral vascular disease (PVD). Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in brain tissue include, but are not limited to, adrenal and intracranial calcification in familial cerebral cavernous malformations, cerebrovascular disease, familial cerebral cavernous malformations (FCCM), idiopathic brain calcification (Fahr's disease), pineal calcification, and primary familial brain calcification (PFBC). Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in carotid tissue include, but are not limited to ischemia, peripheral arterial disease (PAD), peripheral vascular disease (PVD), stroke, and thrombosis. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in femoral tissue include, but are not limited to, arteriosclerosis, arterial stiffness, atherosclerosis, cardiovascular calcification, cardiovascular disease in chronic kidney disease (CKD) patients, cardiovascular disease linked to aging, cardiovascular mortality, critical limb ischemia (CLI), general arterial calcification of infancy (GACI), ischemia, peripheral arterial disease (PAD), peripheral vascular disease (PVD), thrombosis, and vascular calcification. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in heart and heart valve tissues include, but are not limited to, aneurysm, angina pectoris (chronic stable angina), aortic valve calcification, arrhythmia, arteriosclerosis, arterial stiffness, atherosclerosis, calcific aortic valve stenosis (CAVS or AVS), cardiac death, cardiac disease, cardiovascular calcification, cardiovascular disease in chronic kidney disease (CKD) patients, cardiovascular disease linked to aging, cardiovascular mortality, cerebrovascular disease, congestive heart failure, coronary artery calcification, coronary artery disease, coronary disease, electrocardiographic abnormalities, general arterial calcification of infancy (GACI), heart failure, hypertension, ischemia, left ventricular hypertrophy, myocardial infarction, and myocardial ischemia. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in joint tissue include, but are not limited to, calcific tendinitis, calcification in osteoarthritis, calcification of articular cartilage in osteoarthritis, calcification of joints and arteries (CALJA), dystrophic calcification, ad pseudogout. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in kidney tissue include, but are not limited to, failure of renal transplant grafts, kidney stones (i.e., renal lithiasis), nephrocalcinosis, and primary hyperoxaluria (PH). Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in lung tissue include, but are not limited to, dystrophic calcification, and metastatic calcification. Examples of diseases and / or conditions related to ectopic calcification or the consequences thereof in skin tissue include, but are not limited to, calciphylaxis (CUA) and pseudoxanthoma elasticum (PXE). In some aspects, the IP5 substituted compound is of general formulas IV to XI or any combination thereof. In some aspects, the IP5 substituted is Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof.

[0155] As indicated above, the administration of the IP5 substituted compounds of the present invention to a subject inhibits the formation and / or growth of hydroxyapatite (HAP) crystals and their deposition in ectopic calcifications. This mechanism of action could mediate the therapy of many diseases and / conditions related to ectopic calcification and the consequences therefor. For instance, as HAP formation is inhibited, arterial stiffening would be reduced, thus improving the perfusion of coronary arteries during diastole and relieving any associated symptoms of ischemia, such as angina pectoris. Similarly, the IP5 substituted compounds of the present invention may also be effective in reducing the risk of cardiovascular events in patients. By inhibiting HAP formation, the IP5 substituted compounds of the present invention would slow down the progression of coronary artery calcification (CAC). Since CAC is associated with increased cardiovascular mortality, a reduction in its rate of progression may reduce the risk of cardiovascular events. Moreover, the IP5 substituted compounds of the present invention may additionally slow down the calcification of aortic valve leaflets, in view of their inhibitory properties over HAP formation. Pseudoxanthoma elasticum (PXE) is characterized by ectopic mineralization and fragmentation of elastic fibers in the skin, eye, vascular, and gastrointestinal system. As the IP5 substituted compounds of the present invention inhibit HAP formation, the eyesight of PXE patients, for example, could be stabilized or improved.

[0156] In some aspects, the present invention refers to IP5 substituted compounds of general formula I (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) or the pharmaceutical compositions of the invention for use in the treatment, inhibition of progression, and prevention of a disease and / or condition related to ectopic calcification or the consequences thereof in a subject in need thereof, wherein (i) a therapeutically effective amount of the IP5 substituted or pharmaceutical composition of the invention is administered to the subject and (ii) the disease and / or condition is selected from the group consisting of angina pectoris (chronic stable angina), calcific aortic valve stenosis, calciphylaxis, cardiovascular disease in CKD patients, peripheral arterial disease, critical limb ischemia, general arterial calcification of infancy, pseudogout, primary hyperoxaluria, and pseudoxanthoma elasticum. In some aspects, the IP5 substituted compound is of general formulas IV to XI or any combination thereof. In some aspects, the IP5 substituted is Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof.

[0157] In some aspects, the present invention relates to a method for the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof, which comprises administering a therapeutically effective amount of an IP5 substituted compound or pharmaceutical composition of the invention. In some aspects, an IP5 substituted compound of formulas IV to XI, or any combination thereof, is administered to the subject. In some further aspects, Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof, is administered to the subject.

[0158] In some aspects, the consequence of the ectopic calcification is, e.g., (i) a functional complication, (ii) pain, (iii) a trophic complication, (iv) an infection, or (v) a combination thereof. In some aspects, the function complication is, e.g., a limitation of range of motion and / or joint function. In some aspects, the trophic complication is, e.g., ischemia and / or a lesion. In some aspects, the lesion is, e.g., necrosis of the cutaneous and / or subcutaneous tissues.

[0159] In some aspects, the administration of the IP5 substituted compound or pharmaceutical composition of the present invention to a subject in need thereof causes a reduction in lesions, e.g., as determined by the Bates-Jensen Wound Assessment tool or other methods known in the art (Bates-Jensen B, Decubitus 1992; 5(6):20-28). In some aspects, the reduction in lesions comprises, e.g., a reduction in the severity of the lesions, a reduction in the size of the lesions, and reduction in the duration of the lesions, or a combination thereof. In some aspects, the administration of the IP5 substituted compound or pharmaceutical composition of the present invention to a subject in need thereof causes an improvement in lesion healing. In some aspects, the administration of the IP5 substituted compound or pharmaceutical composition of the present invention to the subject causes a reduction in pain. In some aspects, the subject has renal failure. In some aspects, the subject is on hemodialysis. In some aspects, subject is human.

[0160] In some aspects, the administration of the IP5 substituted compound or pharmaceutical composition of the present invention to a subject in need thereof causes an improvement on global wound quality of life (QoL) as determined by using a validated wound-associated QoL questionnaire or other methods known in the art (Augustin M, et al., Int Wound J.2017; 14(6):1299-1304). In some aspects, the subject has renal failure. In some aspects, the subject is on hemodialysis. In some aspects, subject is human.

[0161] Kidney failure, also known as renal impairment or kidney disease, is a disease that causes a progressive loss of kidney function, with a concomitant decrease in the glomerular filtration rate (GFR) or index. Renal impairment, together with treatment of the disease, leads to hypercalcemia and hyperphosphatemia. Hypercalcemia and hyperphosphatemia may cause cardiovascular calcification, although a deficiency of repressor factors (e.g., matrix Gla protein, osteopontin, fetuin, or vitamin K) or an imbalance in promoting factors (e.g., vitamin D, FGF23, inflammatory cytokines, lipid deposits, apoptotic bodies, nucleational complexes) may delay or accelerate the process. Patients with renal impairment are commonly described as patients with CKD-MBD (chronic kidney disease-mineral bone disease) as altered kidney function provokes a cascade of effects that also affect bone remodeling.

[0162] In some aspects, the IP5 substituted compounds and pharmaceutical compositions of the present invention can be used for treating, inhibiting the progression, and preventing some of the diseases and / or conditions related to ectopic calcification or the consequences thereof, as listed above, in patients with kidney failure. In some aspects, the disease and / or condition related to ectopic calcification or the consequences thereof is a kidney failure-related disease. In some aspects, the patient with kidney failure is on dialysis. In some aspects, the IP5 substituted compounds and pharmaceutical compositions of the invention are administered to the patient with kidney failure via intravenous infusion. In some aspects the intravenous infusion is performed using a dialysis apparatus. In some aspects, the IP5 substituted is a compound of general formulas IV to XI or any combination thereof. In some aspects, the IP5 substituted is Compound 1, Compound 6, Compound 47, Compound 48, Compound 53 or any combination thereof. In some aspects, a therapeutically effective amount of the IP5 substituted compound of the invention is administered to the patient with kidney failure.

[0163] In some aspects, the IP5 substituted compounds of the present invention can be used in dialysis liquids, e.g., during hemodialysis. Accordingly, the present invention also provides dialysis liquids, e.g., hemodialysis liquids comprising an IP5 substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53), a pharmaceutically acceptable salt thereof, or any combination thereof, wherein the administration of the IP5 substituted compound, pharmaceutically acceptable salt thereof, or combination thereof to the subject in need thereof is effective in treating, inhibiting the progression, and preventing (i) ectopic calcification and the consequences thereof or (ii) a disease and / or condition related to ectopic calcification or the consequences thereof. A. Synthesis of protected myo-inositol agents, alkylating or click agents and activated acids A.1. Synthesis of protected myo-inositol agents (1), (2), (3), (4), (31), (32), (33), and (34)

[0164] 1,3,5-O-Methylidyne-myo-inositol (1): The synthesis of (1) was previously described in the literature (Martin S, et al., J. Org. Chem.1994; 59(17):4805-4820)

[0165] 2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-myo-inositol (2): The synthesis of (2) was previously described in the literature (Kadirvel, 2008, supra).

[0166] 4,6-bis-O-(4-Methoxybenzyl)-1,3,5-O-methylidyne-myo-inositol (3): The synthesis of (3) was previously described in the literature (Aiba, 2016, supra).

[0167] 4,6-di-O-Benzyl-1,3,5-O-methylidyne-myo-inositol (4): The synthesis of (4) was previously described in the literature (Chen, 2015, supra).

[0168] 2,4,6-tri-O-Benzyl-1,3,5-O-methylidyne-myo-inositol (31): The synthesis of (31) was previously described in the literature (Song F, et al., Org Biomol Chem 2012; 10:3642-3654).

[0169] 2,4,6-tri-O-Benzyl-myo-inositol (32): The synthesis of (32) was previously described in the literature (Chen, 2015, supra).

[0170] 1,2,3,4,6-penta-O-Benzyl-myo-inositol (33): The synthesis of (33) was previously described in the literature (Gurale B, et al., Carbohydrate Res 2018; 461:38- 44).

[0171] rac-2,4,6-tri-O-Benzyl-3,5-O-ethylidene-myo-inositol (34): The synthesis of (34) was previously described in the literature (Song, 2012, supra). A.2. Alkylating or click agents’ synthesis

[0172] 1-(4-(2-Chloroethyl)piperazin-1-yl)ethanone (5): To a solution of 1-(4-(2- hydroxyethyl)piperazin-1-yl)ethanone (1.74 g, 10.10 mmol) in dichloromethane (DCM, 0.2 M) at 0ºC, triethylamine (TEA, 2.1 mL, 15.15 mmol) and Ts-Cl (2.31 g, 12.12 mmol) were added. The reaction mixture was stirred for 72 h at room temperature and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, DCM: MeOH (MeOH) (95:5) rending 1.28 g of (5) (66% yield). HPLC-MS (Condition A): rt= 0.24 min; m / z: 191, 193 [M, M+2]+.

[0173] 9-Methoxynonyl 4-methylbenzenesulfonate (7):

[0174] Step 1: 9-Methoxynonan-1-ol (6): A mixture of 9-bromononan-1-ol (0.5 g, 2.24 mmol) and sodium methoxide 4 N (25 mL, 100 mmol)) was stirred for 18 h at 40ºC. The reaction mixture was filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, hexane (Hex):ethyl acetate (EtOAc) 4:1) to afford 324 mg of (6) (83% yield). 1H NMR (400 MHz, Chloroform-d) δ 3.63 (t, J = 6.6 Hz, 2H), 3.36 (t, J = 6.6 Hz, 2H), 3.33 (s, 3H), 1.59–1.52 (m, 4H), 1.29 (m, 10H). Step 2: 9-Methoxynonyl 4-methylbenzenesulfonate (7): To a solution of (6) (1.5 g, 8.61 mmol) in DCM (28.7 mL), TEA (1.80 mL, 12.91 mmol) and Ts-Cl (2.13 g, 11.19 mmol) were added. The reaction mixture was stirred for 24 h at rt then quenched with water and washed with brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 4:1) to afford 2.15 g of (7) (76%).1H NMR (400 MHz, Chloroform-d) δ 7.78 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 4.01 (t, J = 6.5 Hz, 2H), 3.35 (t, J = 6.6 Hz, 2H), 3.32 (s, 3H), 2.45 (s, 3H), 1.61 (dt, J = 8, 6.6 Hz, 2H), 1.56-1.51 (m, 2H), 1.32–1.22 (m, 10H).

[0175] 19-Methoxynonadec-10-yn-1-yl 4-methylbenzenesulfonate (13):

[0176] Step 1: 2-((9-Bromononyl)oxy)tetrahydro-2H-pyran (8): To a mixture of 9- bromononan-1-ol (2.18 g, 9.77 mmol) and p-TsOH (37 mg, 0.19 mmol), 3,4-dihydro-2H- pyran (1.3 mL, 14.65 mmol) was added. The reaction mixture was stirred for 3.5 days at 60ºC. The mixture was diluted with water, extracted with ethyl ether (2x), dried over with Na2SO4, filtered, and the solvents removed in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 9:1) rending 2.4 g of (8) (80% yield).1H-NMR was identical to the previously described in the literature (Grube A, et al., Eur J Org Chem 2006; 1285-1295).

[0177] Step 2: Dec-9-yn-1-yl methanesulfonate (9): To a solution of dec-9-yn-1-ol (5.22 g, 33.8 mmol) in THF (0.35M) at 0ºC, TEA (6.3 mL, 44 mmol) and Ms-Cl (3.5 mL, 44 mmol) were added. The reaction mixture was stirred for 16 h at room temperature and was diluted with water, extracted with DCM (x2), dried over with Na2SO4, filtered, and the solvents removed in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc (20:1) rending 8.1 g of (9) (>99% yield).1H-NMR was identical to the previously described in the literature (Langmuir: the ACS journal of surfaces and colloids., 2013, Vol.29(2), p.570-580).

[0178] Step 3: 10-Methoxydec-1-yne (10): To a (9) (8.17 g, 35.2 mmol), a solution 5 M of sodium methoxide in MeOH (35.2 mL, 176 mmol) was added. The reaction mixture was stirred for 18 h days at 45ºC. The mixture was diluted with water, extracted with ethyl ether (2x), dried over with Na2SO4, filtered, and the solvents removed in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 20:1) rending 4 g of (10) (67% yield).1H NMR (400 MHz, Chloroform-d) δ 3.34 (td, J = 6.6, 1.0 Hz, 2H), 3.31 (s, 3H), 2.15 (tdd, J = 7.1, 2.7, 1.0 Hz, 2H), 1.91 (td, J = 2.7, 1 Hz, 1H), 1.62–1.45 (m, 4H), 1.41–1.23 (m, 8H).

[0179] Step 4: 2-((19-Methoxynonadec-10-yn-1-yl)oxy)tetrahydro-2H-pyran (11): In a tetrahydrofurane (THF) and hexamethylphosphoramide (HMPA) mixed solution (1.2:1) of (10) (1.41 g, 8.42 mmol) cooled to -40° C., a Hex. solution 1.6M of n-BuLi (7.45 mL, 11.93 mmol) was slowly added, followed by stirring at the same temperature for 30 minutes and further stirring at 0°C for 30 minutes. After cooling to -20°C., a HMPA solution of (8) (2.16 g, 7.02 mmol) was slowly added. After stirring at the same temperature for 10 minutes, the temperature was increased to room temperature. Stirring was conducted at the same temperature for 22 hours. Under ice cooling (at 4°C), an aqueous 1N HCl solution and tBuMeO were added, followed by washing in turn with NaHCO3 sat solution and saturated brine and further drying over anhydrous Na2SO4. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) rending 1.28 g of (11) (46% yield).1H NMR (400 MHz, Chloroform-d) δ 4.55 (dd, J = 4.4, 2.8 Hz, 1H), 3.85 (ddd, J = 10.8, 7.6, 3.6 Hz, 1H), 3.71 (dt, J = 9.6, 6.8 Hz, 1H), 3.51–3.45 (m, 1H), 3.35 (dt, J = 9.6, 6.8 Hz, 1H), 3,34 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 2.14–2.08 (m, 4H), 1.82 (tdd, J = 10.8, 7.6, 4.6 Hz, 1H), 1.71 (dt, J = 12.8, 2.8 Hz, 1H), 1.63 – 1.40 (m, 10H), 1.39–1.21 (m, 16H), 0.90 – 0.79 (m, 4H).

[0180] Step 5: 19-Methoxynonadec-10-yn-1-ol (12): To a solution of (11) (3.28 g, 8.31 mmol) in MeOH (0.6M), p-TsOH (95 mg, 0.5 mmol) was added. The reaction mixture was stirred for 3.5 days at 60ºC. The mixture was diluted with water, extracted with ethyl ether (2x), dried over with Na2SO4, filtered, and the solvents removed in vacuo. The filtrate was concentrated yielding 2.6 g of (12) (>99% yield).1H NMR (400 MHz, Chloroform-d) 3.61 (t, J = 6.6 Hz, 2H), 3.34 (t, J = 6.6 Hz, 2H), 3.31 (s, 3H), 2.11 (t, J = 7.2 Hz, 4H), 1.56–1.30 (m, 26H).

[0181] Step 6: 19-Methoxynonadec-10-yn-1-yl 4-methylbenzenesulfonate (13): To a solution of (12) (2.6g, 8.37 mmol) in DCM (0.5M) at 0ºC, TEA (1.4 mL, 10.05 mmol), DMAP (102 mg, 0.83 mmol) and Ts-Cl (1.92 g, 10.05 mmol) were added. The reaction mixture was stirred for 6 h at room temperature and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) rending 2.45 g of (13) (63% yield). HPLC-MS (Condition B): rt= 5.20 min; m / z: 465 [M+1]+, 482 [M+23]+.

[0182] 29-methoxynonacosa-9,20-diyn-1-yl 4-methylbenzenesulfonate (16):

[0183] Step 1:19-Bromo-1-methoxynonadec-9-yne (14): A solution of lithium bromide (0.318 g, 3.66 mmol) in anhydrous THF (0.1M) was dried with 3A molecular sieves (300 mg, previously activated at 400ºC for 24 hours) placed inside the reaction flask. After stirring this solution for 20 minutes, a solution of (13) (0.85 g, 1.829 mmol) in anhydrous THF (2mL+2mL) was added to the previous reaction flask. This solution was stirred at reflux for 4h. Then, the reaction mixture was allowed to reach room temperature and it was diluted with tBuMeO. The organic layer was washed with sat aq NaHCO3, dried over Na2SO4, filtered and the solvent was removed under reduced pressure to afford a yellow oil. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) rending 467 mg of (14) (68% yield).1H NMR (400 MHz, Chloroform-d) δ 3.39 (t, J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 2.12 (t, J = 6.6 Hz, 4H), 1.83 (q, J = 7.2 Hz, 2H), 1.57-1.51 (m, 2H), 1.49–1.22 (m, 24H).

[0184] Step 2: 29-Methoxynonacosa-9,20-diyn-1-ol (15): In an THF / HMPA mixed solution (1.2:1) of dec-9-yn-1-ol (230 mg, 1.48 mmol) cooled to -40° C., an n-hexane solution 1.6M of n-BuLi (1.9 mL, 3.09 mmol) was slowly added, followed by stirring at the same temperature for 30 minutes and further stirring at 0°C. for 30 minutes. After cooling to -20°C, a HMPA solution of (14) (462 mg, 1.24 mmol) was slowly added. After stirring at the same temperature for 10 minutes, the temperature was increased to room temperature. Stirring was conducted at the same temperature for 22 hours. Under ice cooling (at 4°C), an aqueous 1N HCl solution and tBuMeO were added, followed by washing in turn with NaHCO3 sat solution and saturated brine and further drying over anhydrous Na2SO4. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by flash chromatography (silica gel+5% of AgNO3, Hex:EtOAc 4:1) rending 69.7 mg of (15) (12% yield).1H NMR (400 MHz, Deuterium Oxide) δ 3.64 (t, J = 6.6 Hz, 2H), 3.36 (t, J = 6.6 Hz, 2H), 3.33 (s, 3H), 2.13 (t, J = 7.0 Hz, 8H), 1.58- 1.52 (d, J = 8.2 Hz, 4H), 1.51–1.41 (m, 8H), 1.41–1.23 (m, 26H).

[0185] Step 3: 29-Methoxynonacosa-9,20-diyn-1-yl 4-methylbenzenesulfonate (16): To a solution of (15) (69.7 mg, 0.156 mmol) in DCM (0.1M) at 0ºC, TEA (43uL, 0.325 mmol), DMAP (3.3 mg, 0.027 mmol) and Ts-Cl (62 mg, 0.325 mmol) were added. Then, the reaction mixture was diluted with water and tBuMeO. The organic layer was washed with sat aq NaHCO3and brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure to afford a yellow oil. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) rending 63.3 mg of (16) (67% yield).1H NMR (400 MHz, Chloroform-d) δ 7.77 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 3.99 (t, J = 6.6 Hz, 2H), 3.34 (t, J = 6.6 Hz, 2H), 3.30 (s, 3H), 2.43 (s, 3H), 2.12-2.10 (m, 8H), 1.66–1.49 (m, 4H), 1.48–1.39 (m, 8H), 1.39 – 1.12 (m, 26H).

[0186] Bromo-7-methoxyheptane (17): A mixture of 1,7-dibromoheptane (3.27 mL, 19.38 mmol) and sodium methoxide 5N (3.88 mL, 19.38 mmol) was stirred for 4 h at 40ºC. The reaction mixture was filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) to afford 1.4 g of (17) (34.5%).1H NMR (400 MHz, Chloroform-d) δ 3.40 (t, J = 6.9 Hz, 2H), 3.36 (t, J = 6.6 Hz, 2H), 3.33 (s, 3H), 1.89–1.82 (m, 2H), 1.60-1.53 (m, 2H), 1.47-1.40 (m, 2H), 1.39– 1.32 (m, 4H).

[0187] 3-Azidopropyl 4-methylbenzenesulfonate (18): To a solution of 3-azidopropan- 1-ol (1 g, 9.89 mmol) in DCM (0.2M) at 0ºC, TEA (2.07 mL, 14.84 mmol) and Ts-Cl (2.26 g, 11.87 mmol) were added. The reaction mixture was stirred for 24 h at rt then quenched with water and washed with brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 4:1) to afford 1.27 g of (18) (50%).1H NMR (400 MHz, Chloroform-d) δ 7.80 (d, J = 8.3 Hz, 2H), 7.36 (dd, J = 8.3, 0.7 Hz, 2H), 4.11 (t, J = 6.3Hz, 2H), 3.38 (t, J = 6.3 Hz, 2H), 2.46 (s, 3H), 1.89 (p, J = 6.3 Hz, 2H).

[0188] 1-(5-Bromopentyl)-1H-pyrazole (19): To a mixture of 1H-pyrazole (0.78 g, 11.49 mmol) and Cs2CO3 (3.74 mg, 11.49 mmol) in acetonitrile (CAN, 57 mL) 1,5- dibromopentane (1.56 mL, 11.49 mmol) was added. The mixture was stirred for 18 h at rt. The reaction mixture was filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 1:1) to afford 1.1 g of (19) (45%). HPLC-MS (Condition A): rt=3.00 min; m / z: 218, 220 [M+1, M+3]+.

[0189] Benzyl pent-4-ynoate (20): A solution of pent-4-ynoic acid (5,02 g, 51,2 mmol) in DMF (102 mL) was treated with K2CO3 (10.61 g, 77 mmol)) and benzyl bromide (6.09 mL, 51.2 mmol) stirred for 72h, then diluted with water (200 mL) and extracted with diethyl ether (3×150 mL). The combined organic extracts were dried (MgSO4) and filtered. The solvents were removed in vacuo to afford 9.9 g of (20) (>99%). HPLC-MS (Condition A): rt=3.70 min.

[0190] 6-Azidohexyl 4-methylbenzenesulfonate (22):

[0191] Step 1: 6-Azidohexan-1-ol (21): A solution of 6-bromohexan-1-ol (428 µL, 3.27 mmol) and sodium azide (850 mg, 13.08 mmol) in DMF (0.8 M) was stirred for 18 h at 80ºC. Then, the reaction mixture was quenched with water / EtOAc, and washed with brine (3x). The organic layer was dried over with Na2SO4, filtered, and concentrated in vacuum to afford 470 mg of (21) (>99%).1H NMR (400 MHz, Chloroform-d) δ 3.65 (t, J = 6.8 Hz, 2H), 3.27 (t, J = 6.8 Hz, 2H), 1.70–1.56 (m, 4H), 1.40 (m, 4H).

[0192] Step 2: 6-Azidohexyl 4-methylbenzenesulfonate (22): At 0ºC, p-Ts-Cl (720 mg, 3.78 mmol) was added to a solution of (21) (515 mg, 3.60 mmol) and TEA (1.5 mL, 10.79 mmol) in dry DCM (0.6 M). The reaction mixture was stirred overnight at rt. It was diluted with EtOAc and washed with 10% aqueous solution of NaHSO4. The aqueous phase was extracted with EtOAc (3x). The combined layers were washed with saturated aqueous solution of NaHCO3 and dried over anhydrous Na2SO4. The solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel Hex:EtOAc 6:1) giving 666 mg of (22) (62%).1H NMR (400 MHz, Chloroform-d) δ 7.79 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.03 (t, J = 6.4 Hz, 2H), 3.23 (t, J = 6.8 Hz, 2H), 2.45 (s, 3H), 1.66 (p, J = 6.4 Hz, 2H), 1.55 (p, J = 6.4 Hz, 2H), 1.41–1.18 (m, 4H).

[0193] 2-Cyclopropylethyl 4-methylbenzenesulfonate (23): To a solution of 2- cyclopropylethanol (3 mL, 34.0 mmol) in DCM (85 mL), TEA (7.10 mL, 50.9 mmol) and Ts-Cl (7.77 g, 40.8 mmol) were added, and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) yielding 6.23 g (76%) of (23).1H NMR (400 MHz, Chloroform-d) δ 7.78 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 4.06 (t, J = 6.8 Hz, 2H), 2.43 (s, 3H), 1.51 (q, J = 6.8 Hz, 2H), 0.63 (m, 1H), 0.38 (ddd, J = 8, 6, 4 Hz, 2H), -0.01 (dt, J = 6, 4 Hz, 2H).

[0194] 2-Cyclopentylethyl 4-methylbenzenesulfonate (24): To a solution of 2- cyclopentylethanol (1.09 mL, 8.76 mmol) in DCM (22 mL), TEA (1.83 mL, 13.1 mmol) and Ts-Cl (2.00 g, 10.5 mmol) were added, and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layer was washed with brine, dried over with Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) yielding 1.53 g (65%) of (24).1H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J = 8 Hz, 2H), 7.37 (d, J = 8 Hz, 2H), 4.06 (t, J = 6.7 Hz, 2H), 2.47 (s, 3H), 1.89–1.76 (m, 1H), 1.76–1.43 (m, 8H), 1.10–0.99 (m, 2H).

[0195] 3-(4-Methoxyphenyl)propyl 4-methylbenzenesulfonate (25): To a solution of 3-(4-methoxyphenyl)propan-1-ol (0.96 mL, 6.02 mmol) in DCM (15 mL), TEA (1.26 mL, 9.02 mmol) and Ts-Cl (1.38 g, 7.22 mmol) were added, and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layer was washed with brine, dried over with Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) yielding 1.59 g (82%) of (25).1H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J = 8 Hz, 2H), 7.37 (d, J = 8 Hz, 2H), 7.00 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 4.04 (t, J = 6 Hz, 2H), 3.80 (s, 3H), 2.61 (dd, J = 8.2, 6.8 Hz, 2H), 2.48 (s, 3H), 2.03–1.86 (ddt, J = 8.2, 6.8, 6 Hz, 2H).

[0196] 3-(3-(Trifluoromethyl)phenyl)propyl 4-methylbenzenesulfonate (26): To a solution of 3-(3-(trifluoromethyl)phenyl)propan-1-ol (0.91 mL, 4.90 mmol) in DCM (12 mL), TEA (1.02 mL, 7.35 mmol) and Ts-Cl (1.12 g, 5.88 mmol) were added, and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layer was washed with brine, dried over with Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) yielding 1.53 g (87%) of (26).1H NMR (400 MHz, Chloroform-d) δ 7.63 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 7.8 Hz, 1H), 7.21-7.16 (m.2H), 7.19 (d, J = 8.5 Hz, 2H), 7.12 (, J = 7.8 Hz, 1H), 3.88 (t, J = 6.2 Hz, 2H), 2.56 (dd, 8.0, 7.6Hz, 2H), 2.29 (s, 3H), 1.81 (ddt, J = 8.0, 7.6, 6.2 Hz, 2H).

[0197] 3-(p-Tolyl)propyl 4-methylbenzenesulfonate (27): To a solution of 3-(p- tolyl)propan-1-ol (1 g, 6.66 mmol) in DCM (17 mL), TEA (1.39 mL, 9.99 mmol) and Ts- Cl (1.52 g, 7.99 mmol) were added, and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layer was washed with brine, dried over with Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) yielding 1.85 g (87%) of (27).1H NMR (400 MHz, Chloroform-d) δ 7.81 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 4.05 (t, J = 6.4 Hz, 2H), 2.62 (t, J = 7.5 Hz, 2H), 2.48 (s, 3H), 2.32 (s, 3H), 1.95 (tt, J = 7.5, 6.4 Hz, 2H).

[0198] 5-acetamidopentyl 4-methylbenzenesulfonate (29):

[0199] Step 1: N-(5-hydroxypentyl)acetamide (28): To a solution of 5-aminopentan-1- ol (50 g, 485 mmol) and 2,5-dioxopyrrolidin-1-yl acetate (75 g, 485 mmol) in dimethylformamide (DMF, 0.5 M), TEA (101 mL, 727 mmol) was added and the solution was stirred for 18 h at 60ºC. Then, the solvent was evaporated via a high-vacuum rotary evaporator, and residue was dissolved MeOH and treated with IRA-410 till basic pH (aprox 10), filtered, and evaporated to dryness to give 70.4 g of (28) (100%). This crude was used without further purification.1H NMR (400 MHz, CD3OD) δ 3.57 (t, J = 6.5 Hz, 2H), 3.18 (t, J = 7.0 Hz, 2H), 1.94 (s, 3H), 1.65 – 1.47 (m, 4H), 1.49 – 1.32 (m, 2H).

[0200] Step 2: 5-Acetamidopentyl 4-methylbenzenesulfonate (29): To a solution of (28) (70.4 g, 485 mmol) in DCM (0.5 M), TEA (101 mL, 727 mmol) and Ts-Cl (92 g, 485 mmol) were added. The reaction mixture was stirred for 18 h at rt, then, quenched with water / DCM and washed with NaHCO3sat and brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum to afford 92.45 g of (29) (63%).1H NMR (400 MHz, Chloroform-d): δ 7.84 – 7.74 (m, 2H), 7.37 (d, J = 8.1 Hz, 2H), 5.59 (s, 1H), 4.04 (t, J = 6.3 Hz, 2H), 3.21 (q, J = 6.8 Hz, 2H), 2.47 (s, 3H), 1.98 (s, 3H), 1.68 (dt, J = 7.8, 6.6 Hz, 2H), 1.57–1.43 (m, 2H), 1.39 (qd, J = 7.3, 3.0 Hz, 2H). HPLC-MS (Condition A): rt= 3.42 min; m / z: 300 [M+1]+.

[0201] (((10-Bromodecyl)oxy)methyl)benzene (30): The synthesis of (4) was previously described in the literature (Hanbali M., et al., Bioorg Med Chem Letters 2006; 16(10):2637-2640).

[0202] 5-(benzyloxy)pentyl 4-methylbenzenesulfonate (35): To a solution of 5- (benzyloxy)pentan-1-ol (11.2 g, 57.7 mmol) in dichloromethane (DCM, 0.4 M) at 0ºC, triethylamine (TEA, 12 mL, 86 mmol) and Ts-Cl (11 g, 57.7 mmol) were added. The reaction mixture was stirred for 18 h at room temperature and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex / OEtAc (4:1)) rending 15.32 g of (35) (76% yield). HPLC-MS (Condition A): rt= 4.55 min; m / z: 349 [M+1]+, 371 [M+23]+

[0203] 5-Azidopentyl 4-methylbenzenesulfonate (37)

[0204] Step 1: 5-Azidopentan-1-ol (36): A solution of 5-bromopentan-1-ol (0.10 mL, 0.89 mmol) and sodium azide (63 mg, 0.98 mmol) in dimethylformamide (DMF, 0.2 M) was stirred for 18 h at 80ºC. Then, the reaction mixture was quenched with water / EtOAc and was washed with brine (3x). The organic layer was dried over with Na2SO4, filtered, and concentrated in vacuum to afford 57 mg of (36) (50%).1H NMR (400 MHz, Chloroform-d) δ 3.63 (t, J = 6.8 Hz, 2H), 3.26 (t, J = 6.8 Hz, 2H), 1.61 (p, J = 7.2 Hz, 2H), 1.58 (p, J = 6.8 Hz, 2H), 1.52–1.36 (m, 2H). Step 2: 5-Azidopentyl 4-methylbenzenesulfonate (37) *csc_san_02_N37: To a solution of (36) (54 mg, 0.42 mmol) in DCM (0.2 M) at 0ºC, TEA (87 µL, 0.63 mmol) and Ts-Cl (80 mg, 0.42 mmol) were added. The reaction mixture was stirred for 60 h at rt, and then quenched with water / DCM and washed with brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum to afford 92 mg of (37) (78%). HPLC-MS (Condition A): rt= 3.00 min; m / z: 284 [M+1]+.

[0205] Methyl 3-azidopropanoate (38): A mixture of methyl 3-bromopropanoate (10.70 ml, 98 mmol) and sodium azide (8.92 g, 137 mmol) were dissolved in DMSO (Vol: 49.0 ml). The solution was heated to 45 ºC and stirred for 18 h. After the mixture was cooled down to room temperature and extracted with diethyl ether. The combined organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated on a rotary evaporator to give azidopropanoate as colorless liquid.1H NMR (400 MHz, Chloroform- d) δ 3.62 (s, 3H), 3.47 (t, J = 6.3 Hz, 2H), 2.87 (t, J = 6.6 Hz, 2H). B. General procedures B.1. Alkylation procedures

[0206] Procedure A: To a solution of (2), (3), (4), (33) or (34) (1 eq) in dimethylformamide (DMF, 0.2 M) at 0ºC, sodium hydride (2.15 eq) was added. When the addition was complete, the mixture was stirred for 5 minutes at room temperature. Finally, the alkylating agent was added. The reaction was allowed to stir overnight, then quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds.

[0207] Procedure B: To a solution of (2), (3), (4), (33) or (34) (1 eq) in DMF (c=0.15 M) at 0ºC, sodium hydride (1.2 eq) was added. When the addition was complete, the mixture was stirred for 5 min at room temperature. Finally, alkylation agent was added. The reaction was allowed to stir overnight, then quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds.

[0208] Procedure N: To a solution of (2), (3), (4), (33) or (34) (1 eq) in DMF (0.2 M) at 0ºC, LiH was added. When the addition was complete, the mixture was stirred for 5 minutes at rt. Finally, the alkylating agent was added. The reaction was allowed to stir during different times and temperatures depending on the alkylating agent, then quenched with water, and extracted with EtOAc. The organic layer was dried over with Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds. B.2. Debenzylation procedures

[0209] Procedure K: Alkyl-inositol derivative (II_B’, II_C, VIII_B’ or IX_D) was dissolved in a mixture of THF / MeOH (7:3, 0.05M) followed by addition of excess palladium hydroxide on carbon. The mixture was placed under hydrogen atmosphere and stirred 2 days at room temperature. The mixture was then purged with nitrogen, filtered, and concentrated to afford the desired compounds. B.3. Hydrolysis procedures

[0210] Procedure C: Alky-Inositol derivative (II_A, II_B, II_B’, II_D, V_A, V_B, V_D or VIII_B) was dissolved in a mixture of MeOH / Water / DCM / trifluoroacetic acid (3:1:1:1, 0.1M) and the solution was stirred at room temperature overnight. Finally, the solvent and excess of TFA was removed under vacuum to afford the desiderated compounds.

[0211] Procedure D: Alky-Inositol derivative (II_A, II_B, II_B’, II_D, V_A, V_B, V_D or VIII_B) was dissolved in a mixture of MeOH / Water / DCM / trifluoroacetic acid (3:1:1:1, 0.1M) and the solution was stirred at room temperature overnight. Then, the solvent and excess of TFA was removed under vacuum. Finally, the residue was dissolved in MeOH, treated with IRA-400 resin until pH was basic, filtered and the solvent was removed under vacuum to afford the desiderated compounds.

[0212] Procedure E: To a solution of alkyl-inositol derivative (II_A or V_A) in tetrahydrofuran (THF) (c=0.1M), a solution 0.1M of TBAF in THF (1.2 eq) was added. The reaction mixture was stirred for 18 h at room temperature, quenched with water and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was dissolved in a mixture of MeOH / Water / DCM / trifluoroacetic acid (3:1:1:1, 0.1M) and the solution was stirred at room temperature overnight. Then, the solvent and excess of TFA was removed under vacuum. Finally, the residue was dissolved in MeOH (MeOH), treated with IRA-400 resin until pH was basic, filtered and the solvent was removed under vacuum to afford the desiderated compounds.

[0213] Procedure F: alkyl-inositol derivative (II_A, II_B, II_B’, II_D, V_A, V_B, V_D or VIII_B) was dissolved in a mixture of DCM / trifluoroacetic acid (4:1, 0.14 M) and the solution was stirred at room temperature 1h. Then, water was added (final concentration 0.1 M) and the reaction mixture was stirred at room temperature 18h. Finally, layers were separated, and aqueous layer was concentrated in vacuum to afford the desiderated compound.

[0214] Procedure S: alkyl-inositol derivative (II_A, II_B, II_B’, II_D, V_A, V_B, V_D or VIII_B) was dissolved in a mixture of MeOH / HCl 1N (10:1, 0.1 M) and the solution was stirred at rt or 60ºC 48 h. Finally, the solvent and excess of HCl were removed under vacuum. Finally, the residue was dissolved in MeOH, treated with IRA-400 resin until pH was basic, filtered and the solvent was removed under vacuum to afford the desiderated compounds. B.4. Click reaction procedures

[0215] Procedure M: To a solution of Intermediate (VI_A, V_C or X_D) (1 eq), CuSO4·5H2O (0.4 eq) and sodium ascorbate (0.6 eq) in a mixture water (0.07 M), a solution of alkynyl reagent in THF (0.35 M) was added. The reaction mixture was stirred at rt for 24 h under inert atmosphere, filtered over celite, and concentrated in vacuum. The residue was dissolved in MeOH, treated with IRA-400 resin until pH was basic, filtered, and the solvent was removed under vacuum to afford the desired compounds.

[0216] Procedure L: To a solution of Intermediate or IX_D) (1 eq), CuSO4·5H2O (0.4 eq) and sodium ascorbate (0.6 eq) in water (0.07M), a solution of azide-reagent (2 eq) in THF (0.35 M) was added. The reaction mixture was stirred at rt for 20 h under inert atmosphere, filtered over celite, and concentrated in vacuo. The residue was treated with water / DCM. Then, the organic layer was dried over with Na2SO4, filtered, and concentrated in vacuum to afford the desired compound. B.5. Azide reduction procedure

[0217] Procedure P: To a solution of Intermediate (V_B or X_D) (1 eq) in a mixture of THF / water (9:1, 0.08M), DIPEA (3 eq) and PPh3 (2.6 eq) was added. The reaction mixture was stirred for 4 h at 60ºC, then quenched with water, and washed with brine. The organic layer was dried over with Na2SO4, filtered, and concentrated in vacuum to afford the desired compound. No purification was performed. B.6. Amide formation procedure

[0218] Procedure Q: To a solution of Intermediate (II_A, III_B or IX_D) (1 eq) in DMF (0.1 M), TEA (4 eq) and activated acid (2 eq) were added. The reaction mixture was stirred for 4 h at rt and concentrated in vacuum. The residue was dissolved in MeOH, treated with IRA-400 resin until pH was basic, filtered, and the solvent was removed under vacuum. Finally, the residue was purified by flash chromatography (silica gel) to afford pure compounds. B.5. Phosphorylation procedures

[0219] Procedure G: alkyl-inositol derivative (III_A, VI_A, III_B, III_C or III_D) (1 eq) was dissolved in DCM (0.02M) and a solution on tetrazole in ACN (0.43M) (14.4 eq) was added. The mixture was stirred 30 min. at room temperature. Then N,N-diethyl-1,5- dihydrobenzo[e][1,3,2]-dioxaphosphepin-3-amine (7.2 eq) was added and the was stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0ºC and a solution of tert-butyl hydroperoxide in hexane (5.5M) (19.2 eq) was added. The solution was brought to room temperature and stirred for 1h. The mixture was washed with dilute sodium sulfite and extracted with DCM. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds.

[0220] Procedure H: Alky-Inositol derivative (III_A, VI_A, III_C or III_D) (1 eq) was dissolved in DCM (0.02M) and a solution on tetrazole in ACN (0.43M) (18 eq) was added. The mixture was stirred 30 min at room temperature. Then, N,N-diethyl-1,5- dihydrobenzo[e][1,3,2]-dioxaphosphepin-3-amine (9 eq) was added and the was stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0ºC and a solution of tert-butyl hydroperoxide in hexane (5.5M) (24 eq) was added. The solution was brought to room temperature and stirred for 1h. The mixture was washed with dilute sodium sulfite and extracted with DCM. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds.

[0221] Procedure R: Alky-Inositol derivative III_C or III_D) (1 eq) was dissolved in DMF (0.05M) and a solution on phenyltetrazole in DMF (5M) (18 eq) was added. The mixture was stirred 30 min at room temperature. Then, N,N-diethyl- 1,5-dihydrobenzo[e][1,3,2]-dioxaphosphepin-3-amine (9 eq) was added and the was stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0ºC and a solution of tert-butyl hydroperoxide in hexane (5.5M) (24 eq) was added. The solution was brought to room temperature and stirred for 1h. The mixture was washed with dilute sodium sulfite and extracted with EtOAc (x2). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel) to afford pure compounds. B.6. Phosphate deprotection procedures

[0222] Procedure I: Phosphorylated compound (IV_A, VII-A, IV_B, IV_C or IV_D) was dissolved in a mixture of THF / MeOH / Water (3:1:1, 0.01M) followed by addition of excess palladium hydroxide on carbon or palladium on carbon. The mixture was placed under hydrogen atmosphere and stirred 2 days at room temperature. The mixture was then purged with nitrogen, filtered, and concentrated. The compound was brought at pH 7 by addition of dilute aqueous NaOH (1N) and the residue was purified on a sephadex column (PD-10, G-25-M) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN. The fractions containing product were purified further on a reverse phase cartridge (Sep-Pack, Waters, 1g, C18) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN.

[0223] Procedure J: Phosphorylated compound (IV_A, VII-A, IV_B, IV_C or IV_D) was dissolved in a mixture of THF / MeOH / Water (3:1:1, 0.01M) followed by addition of excess palladium hydroxide on carbon or palladium on carbon. The mixture was placed under hydrogen atmosphere and stirred 2 days at room temperature. The mixture was then purged with nitrogen, filtered, and concentrated. The compound was brought at pH 10 by addition of dilute aqueous NaOH (1N) and the solution was stirred for 24-48h. Finally, the solution was purified on a sephadex column (PD-10, G-25-M) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN. The fractions containing product were purified further on a reverse phase cartridge (Sep-Pack, Waters, 1g, C18) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN.

[0224] Procedure T: Phosphorylated compound (IV_A, VII-A, IV_B, IV_C or IV_D) was treated with thiophenol (40 eq), m-cresol (40 eq) in TFA (0.045 M). Then TBMSBr (40 eq) was added slowly and the mixture was stirred at rt for 4h, quenched with water, and extracted with DCM (3x). The aqueous layer was concentrated in vacuum. The residue was brought at pH 9-10 by addition of water and dilute aqueous NaOH (1N), and the compound was purified on a sephadex column (PD-10, G-25-M) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN. The fractions containing product were purified further in a reverse phase cartridge (Sep-Pack® C18 cartridge, 1 g, Waters Corp., Milford, MA, USA) by eluting with water. All fractions were lyophilized and analyzed by1H-RMN. C. Synthesis of Intermediates II-X C.1. Intermediates II_A, II_B, II_B’, II_C and II_D

[0225] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-pentyl-myo- inositol (II_A-1): According to general alkylation Procedure A, from 377µL (3 eq) of 1- bromopentane, 48 mg of (II_A-1) were obtained (13% yield). HPLC-MS (Condition A): rt= 4.90 min; m / z: 375 [M+1]+.

[0226] rac-4-O-(5-(Benzyloxy)pentyl)-2-O-tert-butyldimethylsilyl-1,3,5-O- methylidyne-myo-inositol (II_A-2): According to general alkylation Procedure A, from 1.04 mL (3 eq) of (((5-bromopentyl)oxy)methyl)benzene, 183 mg of (II_A-2) were obtained (22.8% yield). HPLC-MS (Condition A): rt=4.99 min; m / z: 481 [M+1]+, 503 [M+23]+.

[0227] rac-2-O-tert-Butyldimethylsilyl-4-O-(5-methoxypentyl)-1,3,5-O- methylidyne-myo-inositol (II_A-3): According to general alkylation Procedure A, from 241 mg (2.2 eq, in 3mL of DMF) of 1-bromo-5-methoxypentane, 26 mg of (II_A-3) were obtained (11% yield). HPLC-MS (Condition B): rt= 3.22min; m / z: 405 [M+1]+.

[0228] rac-2-O-tert-Butyldimethylsilyl-4-O-(5-ethoxycarbonylpentyl)-1,3,5-O- methylidyne-myo-inositol (II_A-4): According to general alkylation Procedure A, from 351 µL of ethyl 6-bromohexanoate (3 eq), 107 mg of (II_A-4) were obtained (36% yield). HPLC-MS (Condition A): rt= 4.99 min; m / z: 447 [M+1]+.

[0229] rac-4-O-(2-(4-Acetylpiperazin-1-yl)ethyl)-2-O-tert-butyldimethylsilyl-1,3,5- O-methylidyne-myo-inositol (II_A-5): According to general alkylation Procedure A, from 700mg (2.5 eq in 7.3 mL of DMF) of (5) (2.5 eq, in 7.3 mL of DMF), 460 mg of (II_A-5) were obtained (68% yield). HPLC-MS (Condition A): rt=1.90 min; m / z: 459 [M+1]+.

[0230] 4,6-bis-O-(4-Methoxybenzyl)-1,3,5-O-methylidyne-2-O-pentyl-myo-inositol (II_B-1): According to general alkylation Procedure B, from 200 mg of (3) and 87µL (1.5eq) of 1-bromopentane, 142 mg (II_B-1) were obtained (61% yield). HPLC-MS (Condition B): rt= 3.43 min; m / z: 501 [M+1]+, 523[M+23]+.

[0231] 4,6-bis-O-(4-Methoxybenzyl)-2-O-(5-methoxypentyl)-1,3,5-O-methylidyne- myo-inositol (II_B-2): According to general alkylation Procedure B, from 400 mg of (3) and 505 mg (3 eq) of 1-bromo-5-methoxypentane, 180 mg of (II_B-2) were obtained (36.5% yield). HPLC-MS (Condition A): rt=4.26 min; m / z: 531 [M+1]+, 553 [M+23]+.

[0232] 4,6-bis-O-(4-Methoxybenzyl)-2-O-(9-methoxynonyl)-1,3,5-O-methylidyne- myo-inositol (II_B-3): According to general alkylation Procedure B, from 500 mg of (3) and 420 mg (1.1 eq) of (7), 430 mg of (II_B-3) were obtained (63% yield).1H NMR (400 MHz, Chloroform-d) δ 7.20 (d, J = 8.6 Hz, 4H), 6.82 (d, J = 8.6 Hz, 4H), 5.48 (d, J = 1.2 Hz, 1H), 4.60 (d, J = 11.3 Hz, 2H), 4.47 (d, J = 11.3 Hz, 2H), 4.38-4.35 (m, 1H), 4.30 (t, J = 3.6 Hz, 2H), 4.24-4.22 (m, 2H), 3.82 (q, J = 1.6 Hz, 1H), 3.79 (s, 6H), 3.47 (t, J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 1.64–1.50 (m, 8H), 1.33–1.21 (m, 6H).

[0233] 4,6-di-O-Benzyl-2-O-(19-methoxynonadec-10-yn-1-yl)-1,3,5-O-methylidyne- myo-inositol (II_B’-1): According to general alkylation Procedure B, from 437 mg of (4) and 631 mg (1.1 eq) of (13), 504 mg of (II_B’-1) were obtained (66% yield).1H NMR (400 MHz, Chloroform-d) δ 7.28 (s, 10H), 5.49 (d, J = 1.3 Hz, 1H), 4.68 (d, J = 11.8 Hz, 3H), 4.55 (d, J = 11.8 Hz, 2H), 4.45–4.40 (m, 1H), 4.34 (t, J = 3.6 Hz, 2H), 4.27 (m, 2H), 3.85 (q, J = 1.6 Hz, 1H), 3.48 (t, J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 2.11 (t, J = 7.0 Hz, 4H), 1.60 (q, J = 7.0 Hz, 2H), 1.54-1.51 (m, 2H), 1.44 (q, J = 7.0 Hz, 4H), 1.37–1.24 (m, 16H).

[0234] 4,6-di-O-Benzyl-2-O-(29-methoxynonacosa-9,20-diyn-1-yl)-1,3,5-O- methylidyne-myo-inositol (II_B’-2): According to general alkylation Procedure B, from 404 mg of (4) and 721 mg (1.1 eq) of (16), 776 mg of (II_B’-2) were obtained (89% yield).1H NMR (400 MHz, Chloroform-d) δ 7.28 (s, 10H), 5.49 (d, J = 1.3 Hz, 1H), 4.68 (d, J = 11.8 Hz, 2H), 4.55 (d, J = 11.8 Hz, 2H), 4.44-4.42 (m, 1H), 4.34 (t, J = 3.7 Hz, 2H), 4.27 (m, 2H), 3.85 (q, J = 1.7 Hz, 1H), 3.47 (t, J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 2.11 (t, J = 7.2 Hz, 8H), 1.61 (p, J = 6.9 Hz, 2H), 1.55-1.50 (m, 2H), 1.45 (p, J = 7.0 Hz, 8H), 1.38–1.25 (m, 26H).

[0235] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-(3-(p-tolyl)propyl)- myo-inositol (II_A-6): According to general alkylation Procedure N, from 1.848g (2.5 eq.) of (27), 374 mg of (II_A-6) were obtained (35% yield). HPLC-MS (Condition A): rt= 4.99 min; m / z: 437 [M+1]+, 459 [M+23]+

[0236] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-(4-methylpentyl)- myo-inositol (II_A-7): According to general alkylation Procedure N, from 1 mL (2.5 eq.) of 1-bromo-4-methylpentane, 781 mg of (II_A-7) were obtained (71% yield). HPLC-MS (Condition A): rt= 5.09 min; m / z: 389 [M+1]+, 411 [M+23]+.

[0237] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-(6,6,6- trifluorohexyl)-myo-inositol (II_A-8): According to general alkylation Procedure N, from 1.158 g (2.5 eq.) of 6-bromo-1,1,1-trifluorohexane, 574 mg of (II_A-8) were obtained (61% yield). HPLC-MS (Condition A): rt= 4.73 min; m / z: 443 [M+1]+, 465 [M+23]+.

[0238] rac-2-O-tert-Butyldimethylsilyl-4-O-(3-(4-methoxyphenyl)propyl)-1,3,5-O- methylidyne-myo-inositol (II_A-9): According to general alkylation Procedure N, from 1.59 g (2.5 eq.) of (25), 457 mg of (II_A-9) were obtained (51% yield). HPLC-MS (Condition A): rt= 4.72 min; m / z: 453 [M+1]+, 455 [M+23]+.

[0239] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-(3-(3- (trifluoromethyl)phenyl)propyl)-myo-inositol (II_A-10): According to general alkylation Procedure N, from 1.53g (2.5 eq.) of (26), 807 mg of (II_A-10) were obtained (96% yield). HPLC-MS (Condition A): rt= 4.99 min; m / z: 491 [M+1]+.

[0240] rac-2-O-tert-Butyldimethylsilyl-4-O-(2-cyclopentylethyl)-1,3,5-O- methylidyne-myo-inositol (II_A-11): According to general alkylation Procedure N, from 1.53 g (2.5 eq.) of (24), 50 mg of (II_A-11) were obtained (5% yield). HPLC-MS (Condition A): rt= 5.26 min; m / z: 401 [M+1]+, 423 [M+23]+.

[0241] rac-2-O-tert-Butyldimethylsilyl-4-O-(2-cyclopropylethyl)-1,3,5-O- methylidyne-myo-inositol (II_A-12): According to general alkylation Procedure A, from 1.45 g (1 eq.) of (23), 552 mg of (II_A-12) were obtained (25% yield). HPLC-MS (Condition A): rt= 4.65 min; m / z: 373 [M+1]+, 395 [M+23]+.

[0242] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-(5-(1H-pyrazol-1- yl)pentyl)-myo-inositol (II_A-13): According to general alkylation Procedure A, from 214 mg of (19), 174 mg of (II_A-13) were obtained (60% yield). HPLC-MS (Condition A): rt= 4.11 min; m / z: 441 [M+1]+.

[0243] rac-4-O-(5-Acetamidopentyl)-2-O-tert-butyldimethylsilyl-1,3,5-O- methylidyne-myo-inositol (II_A-14): According to general alkylation Procedure N, from 1 g (3 eq.) of (29), 241 mg of (II_A-14) were obtained (50% yield). HPLC-MS (Condition A): rt= 3.78 min; m / z: 432 [M+1]+.

[0244] rac-2-O-tert-Butyldimethylsilyl-4-O-(10-ethoxycarbonyldecyl)-1,3,5-O- methylidyne-myo-inositol (II_A-15): According to general alkylation Procedure A, from 500 mg (2.5 eq.) of ethyl 11-bromoundecanoate, 50 mg of (II_A-15) were obtained (14% yield).1H NMR (400 MHz, Chloroform-d) δ 1H NMR (400 MHz, Chloroform-d) δ 5.47 (d, J = 1.6 Hz, 1H), 4.39 (ddt, J = 10.1, 4.1, 2.8 Hz, 1H), 4.24 (t, J = 2.8 Hz, 2H), 4.18 (dt, J = 5.2, 2.1 Hz, 1H), 4.14 (q, J = 1.6 Hz, 1H), 4.11-4.08 (m, 1H), 4.09 (q, J = 7.1 Hz, 1H), 3.70 (d, J = 10.1 Hz, 1H), 3.59 (td, J = 9,5, 6.5 Hz, 1H), 3.58 (td, J = 9,5, 6.5 Hz, 1H), 2.25 (t, J = 7.6 Hz, 2H), 1.58 (p, J = 6.8 Hz, 2H), 1.55 (p, J = 6.8 Hz, 2H), 1.30– 1.23 (m, 12H), 1.22 (t, J = 7.1 Hz, 3H), 0.92 (s, 9H), 0.13 (s, 6H).

[0245] rac-4-O-(10-(Benzyloxy)decyl)-2-O-tert-butyldimethylsilyl-1,3,5-O- methylidyne-myo-inositol (II_A-16): According to general alkylation Procedure A, from 407.9 mg (2.1 eq.) of (30), 44.5 mg of (II_A-16) were obtained (14% yield). HPLC- MS (Condition A): rt= 6.13 min; m / z: 551 [M+1]+.

[0246] rac-2-O-tert-Butyldimethylsilyl-4-O-methyl-1,3,5-O-methylidyne-myo- inositol (II_A-17): According to general alkylation Procedure A, from 0.1 mL (1 eq.) of methyl iodide, 50 mg of (II_A-17) were obtained (10% yield). HPLC-MS (Condition A): rt= 3.83 min; m / z: 319 [M+1]+, 341 [M+23]+.

[0247] rac-2-O-tert-Butyldimethylsilyl-4-O-(7-methoxyheptyl)-1,3,5-O- methylidyne-myo-inositol (II_A-18): According to general alkylation Procedure A, from 780 mg (2.5 eq.) of (17), 163 mg of (II_A-18) were obtained (25% yield). HPLC- MS (Condition A): rt= 4.79 min; m / z: 433 [M+1]+, 455 [M+23]+.

[0248] rac-2-O-tert-Butyldimethylsilyl-1,3,5-O-methylidyne-4-O-propyl-myo- inositol (II_A-19): According to general alkylation Procedure A, from 481 uL (5 eq.) of 1-iodopropane, 139 mg of (II_A-19) were obtained (41% yield). HPLC-MS (Condition A): rt= 4.41 min; m / z: 347 [M+1]+, 369 [M+23]+.

[0249] 1,2,3,4,6-penta-O-Benzyl-5-O-propargyl-myo-inositol (II_C-1): According to general alkylation Procedure B, from 200 mg of (33) and 141 uL 3-bromoprop-1-yne in toluene (3 eq, 80%), 107 mg of (II_C-1) were obtained (50% yield). HPLC-MS (Condition A): rt= 5.98 min; m / z: 670 [M+1]+, 692 [M+23]+.

[0250] 1,2,3,4,6-penta-O-Benzyl-5-O-(2-cyclopropylethyl)-myo-inositol (II_C-2): According to general alkylation Procedure B, from 200 mg of (33) and 114 mg (1.5 eq) of (23), 108 mg of (II_C-2) were obtained (49% yield). HPLC-MS (Condition A): rt= 6.56 min; m / z: 700 [M+1]+, 722 [M+23]+.

[0251] 1,2,3,4,6-penta-O-Benzyl-5-O-(9-methoxynonyl)-myo-inositol (II_C-3): According to general alkylation Procedure B, from 200 mg of (33) and 156 mg (1.5 eq) of (7), 127 mg of (II_C-3) were obtained (51% yield). HPLC-MS (Condition A): rt= 7.11 min; m / z: 789[M+1]+, 810 [M+23]+.

[0252] rac-2,4,6-tri-O-Benzyl-3,5-O-ethylidene-1-O-propargyl-myo-inositol (II_D- 1): According to general alkylation Procedure B, from 162 mg of (34) and 152 uL 3- bromoprop-1-yne in toluene (3 eq, 80%), 146 mg of (II_C-1) were obtained (83% yield). HPLC-MS (Condition A): rt= 5.08 min; m / z: 537 [M+23]+.

[0253] rac-2-O-tert-Butyldimethylsilyl-4-O-(5-carboxypentyl)-1,3,5-O-methylidyne- myo-inositol (II_A-20): To a solution of Intermediate (II_A-4) (1.58g, 3.56 mmol) in MeOH / THF (0.15 M), a solution of lithium hydroxide (1M, 11 mL, 10.96 mmol) was added and the solution was stirred for 18 h at rt, then, quenched with HCl 1M / DCM and washed with brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, Hex / EtOAc 1:1) to afford 575mg of (II_A-20) (38%). HPLC-MS (Condition A): rt= 3.91 min; m / z: 419 [M+1]+.

[0254] rac-4-O-(6-Amino-6-oxohexyl)-2-O-tert-butyldimethylsilyl-1,3,5-O- methylidyne-myo-inositol (II_A-21): To a mixture of Intermediate (II_A-20) (80 mg, 0.19 mmol), TEA (53 uL, 0.38 mmol) and bis(2,5-dioxopyrrolidin-1-yl) carbonate (59 mg, 0.23 mmol) in DCM (0.15 M), a solution of ammonia in dioxane (2.8 mL, 1.91 mmol) was added and the solution was stirred for 18 h at rt, then, quenched with water / DCM and washed with brine. The organic layer was dried over with Na2SO4, filtered and concentrated in vacuum to afford 72 mg of (II_A-21) (90%). HPLC-MS (Condition A): rt= 3.66 min; m / z: 418 [M+1]+.

[0255] 4,6-bis-O-(4-Methoxybenzyl)-2-O-propargyl-myo-inositol (II_B-4): According to general alkylation Procedure A, from 248 mg of (3) and 171 mg (2 eq) of propargyl bromide, 184 mg of (II_B-4) were obtained (68% yield). HPLC-MS (Condition A): rt= 4.07 min; m / z: 469 [M+1]+.

[0256] 2-O-(5-(Benzyloxy)pentyl)-4,6-bis-O-(4-methoxybenzyl)-1,3,5-O- methylidyne-myo-inositol (II_B-5): According to general alkylation Procedure A, from 162 mg of (3) and 262 mg (2 eq) of (35), 179 mg of (II_B-5) were obtained (78% yield). HPLC-MS (Condition A): rt= 4.90 min; m / z: 607 [M+1]+, 629 [M+23]+.

[0257] 2-O-(5-Aminopentyl)-4,6-bis-O-(4-methoxybenzyl)-1,3,5-O-methylidyne- myo-inositol (II_B-6): According to general azide reduction Procedure P, from 110 mg of (V_B-1), 203 mg of (II_B-6) were obtained (100%). HPLC-MS (Condition A): rt= 3.24 min; m / z: 516 [M+1]+.

[0258] 4,6-bis-O-(4-Methoxybenzyl)-2-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1- yl)pentyl)-1,3,5-O-methylidyne-myo-inositol (II_B-7): According to general click reaction Procedure M, from 126 mg of (V_B-1) and 16 mg (1 eq.) of 3-methoxyprop-1- yne, 142 mg of (II_B-7) were obtained (100%). HPLC-MS (Condition A): rt= 3.97 min; m / z: 612 [M+1]+.

[0259] 4,6-di-O-Benzyl-2-O-(6,6,6-trifluorohexyl)-O-1,3,5-methylidyne-myo-inositol (II_B’-3): According to general alkylation Procedure B, from 200 mg of (4) and 142 mg (1.2 eq) of 6-bromo-1,1,1-trifluorohexane, 89.9 mg of (II_B’-3) were obtained (33% yield). HPLC-MS (Condition A): rt= 4.90 min; m / z: 509 [M+1]+, 532 [M+23]+.

[0260] 2-O-(6-Amino-6-oxohexyl)-4,6-di-O-benzyl-1,3,5-O-methylidyne-myo- inositol (II_B’-4): According to general alkylation Procedure B, from 200 mg of (4) and 126 mg (1.2 eq) of 6-bromohexanamide, 70 mg of (II_B’-4) were obtained (27% yield). HPLC-MS (Condition A): rt= 3.75 min; m / z: 484 [M+1]+.

[0261] 4,6-di-O-Benzyl-2-O-(2-cyclopentylethyl)-1,3,5-O-methylidyne-myo-inositol (II_B’-5): According to general alkylation Procedure B, from 175 mg of (4) and 152 mg (1.2 eq) of (24), 184 mg of (II_B’-5) were obtained (83% yield). HPLC-MS (Condition A): rt= 5.20 min; m / z: 467 [M+1]+.

[0262] 4,6-di-O-Benzyl-2-O-(2-cyclopropylethyl)-1,3,5-O-methylidyne-myo-inositol (II_B’-6): According to general alkylation Procedure B, from 200 mg of (4) and 195 mg (1.5 eq) of (23), 230 mg of (II_B’-6) were obtained (>99% yield). HPLC-MS (Condition A): rt= 4.74 min; m / z: 439 [M+1]+, 461 [M+23]+.

[0263] 1,2,3,4,6-penta-O-Benzyl-5-O-(5-methoxypentyl)-myo-inositol (II_C-4): According to general alkylation Procedure A, from 250 mg of (33) and 144 mg (1.5 eq) of 1-bromo-5-methoxypentane, 46 mg of (II_C-4) were obtained (16% yield). HPLC-MS (Condition A): rt= 6.36 min; m / z: 732 [M+1]+, 754 [M+23]+.

[0264] 1,2,3,4,6-penta-O-Benzyl-5-O-(6,6,6-trifluorohexyl)-myo-inositol (II_C-5): According to general alkylation Procedure A, from 250 mg of (33) and 174 mg (2 eq) of 6-bromo-1,1,1-trifluorohexane, 162 mg of (II_C-5) were obtained (53% yield). HPLC- MS (Condition A): rt= 6.38 min; m / z: 770 [M+1]+, 792 [M+23]+.

[0265] 1,2,3,4,6-penta-O-Benzyl-5-O-(5-(4-(methoxymethyl)-1,2,3-triazol-1- yl)pentyl)-myo-inositol (II_C-6): According to general click reaction Procedure M, from 110 mg of (V_C-1) and 21 mg (2 eq.) of 3-methoxyprop-1-yne, 102 mg of (II_C-6) were obtained (85%). HPLC-MS (Condition A): rt= 5.59 min; m / z: 813 [M+1]+.

[0266] rac-2,4,6-tri-O-Benzyl-3,5-O-ethylidene-1-O-(9-methoxynonyl)-myo-inositol (II_D-2): According to general alkylation Procedure B, from 203 mg of (34) and 210 mg (1.5 eq) of (7), 270 mg of (II_D-2) were obtained (>99% yield). HPLC-MS (Condition A): rt= 6.06 min; m / z: 656 [M+23]+.

[0267] rac-2,4,6-tri-O-Benzyl-1-O-(2-cyclopropylethyl)-3,5-O-ethylidene-myo- inositol (II_D-3): According to general alkylation Procedure B, from 215 mg of (34) and 163 mg (1.5 eq) of (23), 246 mg of (II_D-3) were obtained (>99% yield). HPLC-MS (Condition A): rt= 5.53 min; m / z: 568 [M+23]+.

[0268] rac-2,4,6-tri-O-Benzyl-3,5-O-ethylidene-2-O-propargyl-myo-inositol (II_D- 4): According to general alkylation Procedure A, from 215 mg of (34) and 201 mg (3 eq) of propargyl bromide, 232 mg of (II_D-4) were obtained (>99% yield). HPLC-MS (Condition A): rt= 4.97 min; m / z: 537 [M+23]+.

[0269] rac-2,4,6-tri-O-Benzyl-3,5-O-ethylidene-1-O-(6,6,6-trifluorohexyl)-myo- inositol (II_D-5): According to general alkylation Procedure A, from 250 mg of (34) and 230 mg (2 eq) of 6-bromo-1,1,1-trifluorohexane, 107 mg of (II_D-5) were obtained (33% yield). HPLC-MS (Condition A): rt=5.62 min; m / z: 637 [M+23]+.

[0270] rac-2,4,6-tri-O-Benzyl-1-O-(2-cyclopentylethyl)-3,5-O-ethylidene-myo- inositol (II_D-6): According to general alkylation Procedure A, from 250 mg of (34) and 211 mg (1.5 eq) of (24), 124 mg of (II_D-6) were obtained (41% yield). HPLC-MS (Condition A): rt= 6.06 min; m / z: 596 [M+23]+. C.2. Intermediates III_A, III_B, III_C and III_D

[0271] rac-4-O-Pentyl-myo-inositol (III_A-1): According to general hydrolysis Procedure E, from 48 mg of (II_A-1), 16.6 mg of (III_A-1) were obtained (53% yield).

[0272] rac-4-O-(5-(Benzyloxy)pentyl)-myo-inositol (III_A-2): According to general hydrolysis Procedure C, from 48 mg of (II_A-2), 20.71 mg of (III_A-2) were obtained (58% yield). HPLC-MS (Condition B): rt= 1.83min; m / z: 357 [M+1]+.

[0273] rac-4-O-(5-Methoxypentyl)-myo-inositol (III_A-3): According to general hydrolysis Procedure C, from 26 mg (II_A-3), 12.3 mg of (III_A-3) were obtained (68% yield). HPLC-MS (Condition B): rt= 0.53 min; m / z: 281 [M+1]+, 303 [M+23]+.

[0274] rac-4-O-(5-Methoxycarbonylpentyl)-myo-inositol (III_A-4): According to general hydrolysis Procedure C introducing a slight modification (aqueous work-up), from 100 mg of (II_A-4), 42 mg of (III_A-4) were obtained (61% yield). HPLC-MS (Condition B): rt= 0.92 min; m / z: 309 [M+1]+.

[0275] rac-4-O-(2-(4-Acetylpiperazin-1-yl)ethyl)-myo-inositol (III_A-5): According to general hydrolysis Procedure C, from 38 mg of (II_A-5), 24 mg of (III_A-5) were obtained (86% yield). HPLC-MS (Condition B): rt=0.23 min; m / z: 335 [M+1]+.

[0276] 2-O-Pentyl-myo-inositol (III_B-1): According to general hydrolysis Procedure F, from 127 mg of (II_B-1), 55.5 mg of (III_B-1) were obtained (87% yield). HPLC-MS (Condition A): rt= 1.65 min; m / z: 251 [M+1]+, 273 [M+23]+.

[0277] 2-O-(5-Methoxypentyl)-myo-inositol (III_B-2): According to general hydrolysis Procedure F, from 180 mg of (II_B-2), 84 mg of (III_B-2) were obtained (88% yield).1H NMR (400 MHz, MeOH-d4) δ 374 (t, J = 6.4 Hz, 2H), 3.67 (t, J = 2.6 Hz, 1H), 3.56 (t, J = 9.6 Hz, 2H), 3.37 (t, J = 6.4 Hz, 2H), 3.35 (dd, 9.6, 2.6 Hz, 2H, 2H), 3.29 (s, 3H), 3.11 (t, J = 9.6 Hz, 1H), 1.62–1.53 (m, 4H), 1.44 – 1.36 (m, 2H).

[0278] 2-O-(9-Methoxynonyl)-myo-inositol (III_B-3): According to general hydrolysis Procedure F, from 430 mg of (II_B-3), 240 mg of (III_B-3) were obtained (97% yield). HPLC-MS (Condition B): rt= 2.53 min; m / z: 337 [M+1]+.

[0279] 2-O-(19-Methoxynonadecyl)-myo-inositol (III_B-4): According to general hydrolysis Procedure C, from 337 mg of (VIII_B-1), 200 mg of (III_B-4) were obtained (60% yield). HPLC-MS (Condition B): rt= 4.43 min; m / z: 477 [M+1]+.

[0280] 2-O-(29-Methoxynonacosyl)-myo-inositol (III_B-5): According to general hydrolysis Procedure C, from 284 mg of (VIII_B-2), 75 mg of (III_B-5) were obtained (27% yield).

[0281] rac-4-O-(3-(p-Tolyl)propyl)-myo-inositol (III_A-6): According to general hydrolysis Procedure S, from 344 mg of (II_A-6), 166.4 mg of (III_A-6) were obtained (67% yield). HPLC-MS (Condition A): rt= 2.87 min; m / z: 313 [M+1]+.

[0282] rac-4-O-(4-Methylpentyl)-myo-inositol (III_A-7): According to general hydrolysis Procedure S, from 767 mg of (II_A-7), 225 mg of (III_A-7) were obtained (43% yield). HPLC-MS (Condition A): rt= 2.60 min; m / z: 265 [M+1]+.

[0283] rac-4-O-(6,6,6-Trifluorohexyl)-myo-inositol (III_A-8): According to general hydrolysis Procedure S, from 424 mg of (II_A-8), 274 mg of (III_A-8) were obtained (90% yield). HPLC-MS (Condition A): rt= 2.66 min; m / z: 319 [M+1]+.

[0284] rac-4-O-(3-(4-Methoxyphenyl)propyl)-myo-inositol (III_A-9): According to general hydrolysis Procedure S, from 409 mg of (II_A-9), 196 mg of (III_A-9) were obtained (66% yield). HPLC-MS (Condition A): rt= 2.66 min; m / z: 329 [M+1]+.

[0285] rac-4-O-(3-(3-(Trifluoromethyl)phenyl)propyl)-myo-inositol (III_A-10): According to general hydrolysis Procedure S, from 209 mg of (II_A-10), 146 mg of (III_A-10) were obtained (93% yield). HPLC-MS (Condition A): rt= 3.01 min; m / z: 367 [M+1]+.

[0286] rac-4-O-(2-Cyclopentylethyl)-myo-inositol (III_A-11): According to general hydrolysis Procedure S, from 68 mg of (II_A-11), 45 mg of (III_A-11) were obtained (96% yield). HPLC-MS (Condition A): rt= 2.65 min; m / z: 277 [M+1]+.

[0287] rac-4-O-(2-Cyclopropylethyl)-myo-inositol (III_A-12): According to general hydrolysis Procedure S, from 486 mg of (II_A-12), 355 mg of (III_A-12) were obtained (96% yield). HPLC-MS (Condition A): rt= 1.09 min; m / z: 249 [M+1]+.

[0288] rac-4-O-(5-(1H-Pyrazol-1-yl)pentyl)-myo-inositol (III_A-13): According to general hydrolysis Procedure S, from 137 mg of (II_A-13), 77 mg of (III_A-13) were obtained (78% yield). HPLC-MS (Condition A): rt= 1.65 min; m / z: 317 [M+1]+.

[0289] rac-4-O-(5-Acetamidopentyl)-myo-inositol (III_A-14): According to general hydrolysis Procedure S, from 254 mg of (II_A-14), 180 mg of (III_A-14) were obtained (>99% yield). HPLC-MS (Condition A): rt= 2.71 min; m / z: 308 [M+1]+.

[0290] rac-4-O-(10-Methoxycarbonyldecyl)-myo-inositol (III_A-15): According to general hydrolysis Procedure S, from 63 mg of (II_A-15), 30 mg of (III_A-15) were obtained (64% yield). HPLC-MS (Condition A): rt= 3.11 min; m / z: 379 [M+1]+.

[0291] rac-4-O-(10-(Benzyloxy)decyl)-myo-inositol (III_A-16): According to general hydrolysis Procedure S, from 25 mg of (II_A-16), 19 mg of (III_A-16) were obtained (98% yield). HPLC-MS (Condition A): rt= 3.54 min; m / z: 427 [M+1]+.

[0292] rac-4-O-Methyl-myo-inositol (III_A-17): According to general hydrolysis Procedure S, from 58 mg of (II_A-17), 27 mg of (III_A-17) were obtained (76% yield).1H NMR (400 MHz, MeOH-d4) δ 3.87 (t, J = 2.8 Hz, 1H), 3.55 (s, 3H), 3.36 (dd, ii = 9.6, 2.8 Hz, 1H), 3.30–3.22 (m, 3H), 3.15 (t, J = 9.2 Hz, 1H).

[0293] rac-4-O-(7-Methoxyheptyl)-myo-inositol (III_A-18): According to general hydrolysis Procedure S, from 167 mg of (II_A-18), 103 mg of (III_A-18) were obtained (87% yield). HPLC-MS (Condition A): rt= 2.57 min; m / z: 309 [M+1]+.

[0294] rac-4-O-Propyl-myo-inositol (III_A-19): According to general hydrolysis Procedure S, from 128 mg of (II_A-19), 66 mg of (III_A-19) were obtained (80% yield). 1H NMR (400 MHz, MeOH-d4) δ 3.88 (t, J = 2.4 Hz, 1H), 3.69 (td, J = 9.2, 7.2 Hz, 1H), 3.68 (td, J = 9.2, 7.2 Hz, 1H), 3.56 (t, J = 9.5 Hz, 1H), 3.39–3.33 (m, 2H), 3.30–3.23 (m, 1H), 3.19-3.12 (m, 1H), 1.58 (h, J = 7.2 Hz, 2H), 0.87 (t, J = 7.2 Hz, 3H).

[0295] rac-4-O-(3-(4-(2-(Benzyloxycarbonyl)ethyl)-1H-1,2,3-triazol-1-yl)propyl)- myo-inositol (III_A-20): According to general click reaction Procedure M, from 57 mg of (VI_A-1) and 61.3 mg (1.5 eq.) of (20), 34 mg of (III_A-20) were obtained (35%). In this case, flash chromatography was employed. HPLC-MS (Condition A): rt= 2.84 min; m / z: 452 [M+1]+.

[0296] rac-4-O-(6-(4-(Methoxycarbonyl)-1H-1,2,3-triazol-1-yl)hexyl)-myo-inositol (III_A-21): According to general click reaction Procedure M, from 99 mg of (VI_A-2) and 27 mg (1 eq.) of methyl propiolate, 109 mg of (III_A-21) were obtained (86%). HPLC-MS (Condition A): rt= 2.39 min; m / z: 390 [M+1]+.

[0297] 5-O-Propyl-myo-inositol (III_C-1): According to general debenzylation Procedure K, from 107 mg of (II_C-1), 15 mg of (III_C-1) were obtained (42% yield).1H NMR (400 MHz MeOH-d4) δ 3.84 (t, J = 2.8, 1H), 3.64 (t, J = 7.4 Hz, 2H), 3.56 (t, J = 9.6 Hz, 2H), 3.24 (dd, J = 9.6, 2.8 Hz, 2H), 2.86 (t, J = 9.6 Hz, 1H), 1.54 (q, J = 7.4 Hz, 3H), 0.83 (t, J = 7.4 Hz, 4H).

[0298] 5-O-(2-Cyclopropylethyl)-myo-inositol (III_C-2): According to general debenzylation Procedure K, from 108 mg of (II_C-2), 15 mg of (III_C-2) were obtained (39% yield).1H NMR (400 MHz, MeOH-d4) δ 3.88 (t, J = 2.8 Hz, 1H), 3.80 (t, J = 7.2 Hz, 2H), 3.61 (t, J = 9.6 Hz, 2H), 3.29 (dd, J = 9.6, 2.8 Hz, 3H), 2.91 (t, J = 9.6 Hz, 1H), 1.47 (q, J = 7.2 Hz, 2H), 0.80–0.62 (m, 1H), 0.41–0.30 (m, 2H), 0.07–-0.10 (m, 2H).

[0299] 5-O-(9-Methoxynonyl)-myo-inositol (III_C-3): According to general debenzylation Procedure K, from 127 mg of (II_C-3), 27 mg of (III_C-3) were obtained (50% yield).1H NMR (400 MHz, MeOH-d4) δ 3.96 (t, J = 2.8 Hz, 1H), 3.80 (t, J = 7.0 Hz, 2H), 3.67 (d, J = 9.6 Hz, 2H), 3.40 (t, J = 6.8 Hz, 2H), 3.35 (dd, J = 9.6, 2.8 Hz, 2H), 2.97 (t, J = 9.6 Hz, 1H), 1.64 (t, J = 7.0 Hz, 3H), 1.57 (p, J = 6.8 Hz, 3H), 1.35 (br, 10H).

[0300] rac-1-O-Propyl-myo-inositol (III_D-1): According to general debenzylation Procedure K, from 107 mg of (IX_D-1), 46 mg of (III_C-1) were obtained (95% yield).1H NMR (400 MHz, MeOH-d4) δ 4.04 (t, J = 2.8 Hz, 1H), 3.59 (t, J = 9.6 Hz, 1H), 3.54 (dt, J = 9.2, 7.2 Hz, 1H), 3.53 (t, J = 9.6 Hz, 1H), 3.38 (dt, J = 9.2, 7.2 Hz, 1H), 3.24 (dd, J = 9.6, 2.8 Hz, 1H), 3.09 (t, J = 9.6 Hz, 1H), 3.01 (dd, J = 9.6, 2.8 Hz, 1H), 1.55 (h, J = 7.2 Hz, 2H), 0.85 (t, J = 7.2 Hz, 3H).

[0301] rac-4-O-(6-Amino-6-oxohexyl)-myo-inositol (III_A-22): According to general hydrolysis Procedure S, from 72 mg of (II_A-21), 50 mg of (III_A-19) were obtained (80% yield).1H NMR (400 MHz, MeOH-d4) δ 3.94 (t, J = 2.5 Hz, 1H), 3.82-3.77 (m, 2H), 3.61 (t, J = 9.5 Hz, 1H), 3.42-3.39 (m, 2H), 3.34-3.30 (m, 1H), 3.23–3.19 (m, 1H), 2.22 (t, J = 7.4 Hz, 2H), 1.68-1.61 (m, 4H), 1.47-1.39 (m, 2H).

[0302] 2-O-(5-(Benzyloxy)pentyl)-myo-inositol (III_B-7): According to general hydrolysis Procedure F, from 179 mg of (II_B-5), 75 mg of (III_B-7) were obtained (71% yield). HPLC-MS (Condition A): rt= 2.83 min; m / z: 357 [M+1]+, 379 [M+23]+.

[0303] 2-O-(6,6,6-Trifluorohexyl)-myo-inositol (III_B-8): According to general debenzylation Procedure K, from 85 mg of (VIII_B’-1), 54 mg of (III_B-8) were obtained (>99% yield). HPLC-MS (Condition A): rt= 2.69 min; m / z: 319 [M+1]+.

[0304] 2-O-(6-Amino-6-oxohexyl)-myo-inositol (III-B-9): According to general debenzylation Procedure K, from 75 mg of (VIII_B’-2), 45 mg of (III_B-9) were obtained (>99% yield).1H NMR (400 MHz, MeOH-d4) δ 3.78 (t, J = 6.4, 1H), 3.76 (t, J = 6.4, 1H), 3.69 (q, J = 3.0 Hz, 1H), 3.59 (td, J = 10.0, 3.0 Hz, 2H), 3.39 (dt, J = 10.0, 3.0 Hz, 2H), 3.14 (td, J = 9.2, 3.6 Hz, 1H), 2.20 (t, J = 7.6 Hz, 2H), 1.67–1.57 (m, 4H), 1.47-1.39 (m, 2H).

[0305] 2-O-(2-Cyclopentylethyl)-myo-inositol (III_B-10): According to general debenzylation Procedure K, from 200 mg of (VIII_B’-3), 120 mg of (III_B-10) were obtained (>99% yield). HPLC-MS (Condition A): rt= 2.69 min; m / z: 277 [M+1]+.

[0306] 2-O-(2-Cyclopropylethyl)-myo-inositol (III_B-11): According to general debenzylation Procedure K, from 261 mg of (VIII_B’-4), 150 mg of (III_B-11) were obtained (>99% yield).1H NMR (400 MHz, MeOH-d4) δ 3.84 (t, J = 6.9 Hz, 2H), 3.70 (t, J = 2.7 Hz, 1H), 3.58 (t, J = 9.5 Hz, 2H), 3.37 (dd, J = 9.5, 2.7 Hz, 2H), 3.12 (t, J = 9.2 Hz, 1H), 1.50 (q, J = 6.9 Hz, 2H), 0.81–0.69 (m, 1H), 0.43–0.39 (m, 2H), 0.07– 0.03 (m, 2H).

[0307] 2-O-(5-Aminopentyl)-myo-inositol (III_B-12): According to general hydrolysis Procedure F, from 105 mg of (II_B-6), 50 mg of (III_B-12) were obtained (93% yield).1H NMR (400 MHz, MeOH-d4) δ 3.79 (t, J = 6.2 Hz, 2H), 3.70 (t, J = 2.7 Hz, 1H), 3.57 (t, J = 9.2 Hz, 2H), 3.40 (dd, J = 10.0, 2.7 Hz, 2H), 3.15 (t, J = 9.2 Hz, 1H), 2.93 (t, J = 7.6 Hz, 2H), 1.74 – 1.61 (m, 4H), 1.53-1.45 (m, 2H).

[0308] 2-O-Propargyl-myo-inositol (III_B-13): According to general hydrolysis Procedure F, from 183 mg of (II_B-4), 73 mg of (III_B-13) were obtained (86% yield).1H NMR (400 MHz, MeOH-d4) δ 4.49 (d, J = 2.6 Hz, 2H), 3.93 (t, J = 2.8 Hz, 1H), 3.57 (t, J = 9.6 Hz, 2H), 3.40 (dd, J = 10.0, 2.8 Hz, 2H), 3.13 (t, J = 9.2 Hz, 1H), 2.81 (t, J = 2.4 Hz, 1H).

[0309] 2-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol According to general hydrolysis Procedure F, from 142 mg of (II_B-7), 65 mg of (III_B-14) were obtained (77% yield). HPLC-MS (Condition A): rt= 1.28 min; m / z: 362 [M+1]+.

[0310] 2-O-(5-Acetamidopentyl)-myo-inositol (III_B-15): According to general Amide formation Procedure Q, from 46 mg of (II_B-12) and 30 mg (1 eq.) of 2,5- dioxopyrrolidin-1-yl acetate, 30 mg of (III_B-15) were obtained (56% yield). HPLC-MS (Condition A): rt= 1.06 min; m / z: 308 [M+1]+.

[0311] 2-O-((1-(2-(Metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo- inositol (III_B-16): According to general click reaction Procedure L, from 109 mg of (III_B-13) and 71 mg (1.1 eq.) of (38), 118 mg of (III_B-16) were obtained (68%). HPLC- MS (Condition A): rt= 0.97 min; m / z: 348 [M+1]+.

[0312] 5-O-(5-Methoxypentyl)-myo-inositol (III_C-4): According to general debenzylation Procedure K, from 46 mg of (II_C-4), 17 mg of (III_C-4) were obtained (>99% yield).1H NMR (400 MHz, MeOH-d4) δ 3.94 (t, J = 2.8 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 3.66 (t, J = 9.5 Hz, 2H), 3.40 (t, J = 6.5 Hz, 2H), 3.36 – 3.32 (dd, J = 10.0, 2.8 Hz, 2H), 3.32 (s, 3H), 2.95 (t, J = 9.2 Hz, 1H), 1.68-1.56 (m, 4H), 1.47–1.40 (m, 2H).

[0313] 5-O-(6,6,6-Trifluorohexyl)-myo-inositol (III_C-5): According to general debenzylation Procedure K, from 160 mg of (II_C-5), 29 mg of (III_C-5) were obtained (43% yield).1H NMR (400 MHz, MeOH-d4) δ 3.94 (t, J = 2.8 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 3.66 (t, J = 9.6 Hz, 2H), 3.34 (dd, J = 10.0, 2.8 Hz, 2H), 2.95 (t, J = 9.2 Hz, 1H), 2.21–2.09 (m, 2H), 1.68– 1.56 (m, 4H), 1.52-1.46 (m, 2H).

[0314] 5-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (III_C-6): According to general debenzylation Procedure K, from 102 mg of (II_C-6), 15 mg of (III_C-6) were obtained (33% yield).1H NMR (400 MHz, MeOH-d4) δ 7.97 (s, 1H), 4.53 (s, 2H), 4.42 (t, J = 7.1 Hz, 2H), 3.94 (t, J = 2.8 Hz, 1H), 3.78 (t, J = 6.6 Hz, 2H), 3.65 (t, J = 9.5 Hz, 2H), 3.37 (s, 3H), 3.33 (dd, J = 10.0.2.8 Hz, 2H), 2.94 (t, J = 9.2 Hz, 1H), 1.95 (p, J = 7.1 Hz, 2H), 1.66 (p, J = 6.6 Hz, 2H), 1.45– 1.38 (m, 2H).

[0315] rac-1-O-(9-Methoxynonyl)-myo-inositol (III_D-2): According to general debenzylation Procedure K, from 196 mg of (IX_D-2), 109 mg of (III_D-2) were obtained (>99% yield). HPLC-MS (Condition A): rt= 2.89 min; m / z: 337 [M+1]+.

[0316] rac-1-O-(2-Cyclopropylethyl)-myo-inositol (III_D-3): According to general debenzylation Procedure K, from 181 mg of (IX_D-3), 87 mg of (III_D-3) were obtained (>99% yield). HPLC-MS (Condition A): rt= 1.06 min; m / z: 249 [M+1]+.

[0317] rac-1-O-(5-Acetamidopentyl)-myo-inositol (III_D-4): According to general debenzylation Procedure K, from 107 mg of (IX_D-4), 57 mg of (III_D-4) were obtained (>99% yield).1H NMR (400 MHz, MeOH-d4) δ 4.13 (s, 1H), 3.70-3.60 (m, 3H), 3.51 (q, J = 7.1 Hz, 1H), 3.35–3.28 (m, 2H), 3-20-3.16 (m, 3H), 3.10 (d, J = 9.5 Hz, 1H), 1.95 (s, 3H), 1.69-1.60 (m, 2H), 1.58-1.49 (m, 2H), 1.47-1.39 (m, 2H).

[0318] rac-1-O-(6,6,6-Trifluorohexyl)-myo-inositol (III_D-5): According to general debenzylation Procedure K, from 102 mg of (IX_D-5), 55 mg of (III_D-5) were obtained (>99% yield). HPLC-MS (Condition A): rt= 2.72 min; m / z: 319 [M+1]+, 341 [M+23]+.

[0319] rac-1-O-(2-Cyclopentylethyl)-myo-inositol (III_D-6): According to general debenzylation Procedure K, from 119 mg of (IX_D-6), 76 mg of (III_D-6) were obtained (64% yield). HPLC-MS (Condition A): rt= 2.72 min; m / z: 277 [M+1]+, 299 [M+23]+.

[0320] rac-1-O-((1-(2-(Metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo- inositol (III_D-7): According to general debenzylation Procedure K, from 248 mg of (IX_D-10), 130 mg of (III_D-7) were obtained (93% yield). HPLC-MS (Condition A): rt= 0.99 min; m / z: 348 [M+1]+.

[0321] rac-1-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (III_D-8): According to general debenzylation Procedure K, from 250 mg of (IX_D-8), 143 mg of (III_D-8) were obtained (>99% yield).1H NMR (400 MHz, MeOH-d4) δ 8.04 (s, 1H), 4.57 (s, 2H), 4.46 (t, J = 7.0 Hz, 2H), 4.17 (t, J = 2.8 Hz, 1H), 3.74– 3.65 (m, 3H), 3.54 (dt, J = 9.4, 6.5 Hz, 1H), 3.41 (s, 3H), 3.40-3.37 (m 1H), 3.24 (t, J = 9.2 Hz, 1H), 3.15 (dd, J = 10.0, 2.8 Hz, 1H), 1.98 (p, J = 7.2 Hz, 2H), 1.69 (p, J = 6.9 Hz, 2H), 1.48– 1.41 (m, 2H). C.3. Intermediates IV_A, IV_B, IV_C and IV_D

[0322] rac-1,2,3,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-pentyl-myo-inositol (IV_A-1): According to general phosphorylation Procedure H, from 76 mg of (III_A-1), 57.6 mg of (IV_A-1) were obtained (16% yield). HPLC-MS (Condition A): rt= 4.15 min; m / z: 1161 [M+1]+.

[0323] rac-4-O-(5-(Benzyloxy)pentyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-2): According to general phosphorylation Procedure H, from 20 mg of (III_A-2), 30 mg of (IV_A-2) were obtained (42% yield). HPLC-MS (Condition B): rt= 3.24 min; m / z: 1267 [M+1]+.

[0324] rac-4-O-(5-Methoxypentyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-3): According to general phosphorylation Procedure H, from 45 mg of (III_A-3), 98 mg of (IV_A-3) were obtained (51% yield). HPLC-MS (Condition B): rt=2.95 min; m / z: 1191 [M+1]+.

[0325] rac-4-O-(5-Methoxycarbonylpentyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)myo-inositol (IV_A-4): According to general phosphorylation Procedure G, from 42 mg of (III_A-4), 23 mg of (IV_A-4) were obtained (14% yield). HPLC-MS (Condition B): rt=2.99 min; m / z: 1219 [M+1]+.

[0326] rac-4-O-(2-(4-Acetylpiperazin-1-yl)ethyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-5): According to general phosphorylation Procedure H, from 24 mg of (III_A-5), 29 mg of (IV_A-5) were obtained (32% yield). HPLC-MS (Condition B): rt=2.37 min. ; m / z: 1245[M+1]+.

[0327] 1,3,4,5,6-pentakis-O-(3-Oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin- 3-yl)-2-O-pentyl-myo-inositol (IV_B-1): According to general phosphorylation Procedure H, from 150 mg of (III_B-1), 399 mg of (IV_B-1) were obtained (57% yield). HPLC-MS (Condition A): rt= 4.15 min; m / z: 1161 [M+1]+.

[0328] 2-O-(5-Methoxypentyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-2): According to general phosphorylation Procedure H, from 84 mg of (III_B-2), 71 mg of (IV_B-2) were obtained (19.9% yield). HPLC-MS (Condition A): rt= 3.99 min; m / z: 1191.6 [M+1]+.

[0329] 2-O-(9-Methoxynonyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-3): According to general phosphorylation Procedure H, from 240 mg of (III_B-3), 110 mg of (IV_B-3) were obtained (12.4% yield). HPLC-MS (Condition B): rt= 3.95 min; m / z: 1247 [M+1]+, 1264 [M+23]+.

[0330] 2-O-(19-Methoxynonadecyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-4): According to general phosphorylation Procedure H, from 200 mg of (III_B-4), 80 mg of (IV_B-4) were obtained (14% yield). HPLC-MS (Condition B): rt= 5.17 min; m / z: 1387 [M+1]+.

[0331] 2-O-(29-Methoxynonacosyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-5): According to general phosphorylation Procedure H, from 75 mg of (III_B-5), 20 mg of (IV_B-5) were obtained (11% yield).31P NMR (162 MHz, Chloroform-d) δ -1.15, -4.17, -4.76.

[0332] rac-1,2,3,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-(3-(p-Tolyl)propyl)-myo-inositol (IV_A-6): According to general phosphorylation Procedure H, from 50 mg of (III_A-6), 44.6 mg of (IV_A-6) were obtained (23% yield).31P NMR (162 MHz, Chloroform-d) δ - 0.71, -1.32, -1.89, -3.00, -4.16. HPLC-MS (Condition A): rt=4.46 min; m / z: 1223 [M+1]+.

[0333] rac-4-O-(4-Methylpentyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-7): According to general phosphorylation Procedure H, from 50 mg of (III_A-7), 45 mg of (IV_A-7) were obtained (20% yield).31P NMR (162 MHz, Chloroform-d) δ -0.50, -1.20, -1.96, -3.05, - 4.16. HPLC-MS (Condition A): rt= 4.44 min; m / z: 1175 [M+1]+.

[0334] rac-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-(6,6,6-Trifluorohexyl)-myo- inositol (IV_A-8): According to general phosphorylation Procedure H, from 50 mg of (III_A-8), 48 mg of (IV_A-8) were obtained (25% yield).31P NMR (162 MHz, Chloroform-d) -0.67, -1.28, -1.85, -2.99, -4.10. HPLC-MS (Condition A): rt=4.31 min; m / z: 1229 [M+1]+.

[0335] rac-4-O-(3-(4-Methoxyphenyl)propyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-9): According to general phosphorylation Procedure H, from 50 mg of (III_A-9), 48 mg of (IV_A-9) were obtained (25% yield).31P NMR (162 MHz, Chloroform-d) δ -0.74, -1.33, -1.85, -3.00, - 3.00, -4.15. HPLC-MS (Condition A): rt= 4.29 min; m / z: 1240 [M+1]+.

[0336] rac-1,2,3,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-(3-(3- (trifluoromethyl)phenyl)propyl)-myo-inositol (IV_A-10): According to general phosphorylation Procedure H, from 50 mg of (III_A-10), 35 mg of (IV_A-10) were obtained (20% yield).31P NMR (162 MHz, Chloroform-d) δ -0.52, -1.24, -1.84, -3.01, - 4.11. HPLC-MS (Condition A): rt= 4.51 min; 1277 m / z: [M+1]+.

[0337] rac-4-O-(2-Cyclopentylethyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-11): According to general phosphorylation Procedure H, from 45 mg of (III_A-11), 33 mg of (IV_A-11) were obtained (17% yield).31P NMR (162 MHz, Chloroform-d) -0.59, -1.18, -1.93, -3.03, -4.15. HPLC-MS (Condition A): rt= 4.46 min; m / z: 1187 [M+1]+.

[0338] rac-4-O-(2-Cyclopropylethyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-12): According to general phosphorylation Procedure H, from 52 mg of (III_A-12), 47 mg of (IV_A-12) were obtained (19% yield).31P NMR (162 MHz, Chloroform-d) δ -0.68, -1.24, -1.90, - 3.00, -4.15. HPLC-MS (Condition A): rt= 4.15 min; m / z: 1159 [M+1]+.

[0339] rac-1,2,3,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-(5-(1H-Pyrazol-1-yl)pentyl)- myo-inositol (IV_A-13): According to general phosphorylation Procedure H, from 50 mg of (III_A-13), 100 mg of (IV_A-13) were obtained (54% yield).31P NMR (162 MHz, Chloroform-d) δ -0.72, -1.39, -1.88, -3.00, -4.13. HPLC-MS (Condition A): rt=4.08 min; m / z: 1227 [M+1]+.

[0340] rac-4-O-(5-Acetamidopentyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-14): According to general phosphorylation Procedure H, from 35 mg of (III_A-14), 14 mg of (IV_A-14) were obtained (10% yield).31P NMR (162 MHz, Chloroform-d) δ -0.75, -1.63, -1.78, - 2.98, -4.04. HPLC-MS (Condition A): rt= 3.82 min; m / z: 1218 [M+1]+.

[0341] rac-4-O-(10-Methoxycarbonyldecyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-15): According to general phosphorylation Procedure H, from 30 mg of (III_A-15), 7.5 mg of (IV_A-15) were obtained (7% yield).31P NMR (162 MHz, Chloroform-d) -0.51, -1.17, -1.92, -3.07, -4.18. HPLC-MS (Condition A): rt= 4.65 min; m / z: 1289 [M+1]+.

[0342] rac-4-O-(10-(Benzyloxy)decyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-16): According to general phosphorylation Procedure H, from 19 mg of (III_A-16), 13 mg of (IV_A-16) were obtained (22% yield).31P NMR (162 MHz, Chloroform-d) δ -0.50, -1.14, -1.93, - 3.07, -4.18. HPLC-MS (Condition A): rt= 5.11 min; m / z: 1337 [M+1]+.

[0343] rac-4-O-Methyl-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-17): According to general phosphorylation Procedure H, from 27 mg of (III_A-17), 10 mg of (IV_A-17) were obtained (6% yield).31P NMR (162 MHz, Chloroform-d) δ -0.83, -1.43, -1.80, - 3.17, -4.20. HPLC-MS (Condition A): rt= 3.96 min; m / z: 1105 [M+1]+.

[0344] rac-4-O-(7-Methoxyheptyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-18): According to general phosphorylation Procedure H, from 50 mg of (III_A-18), 32 mg of (IV_A-18) were obtained (16% yield).31P NMR (162 MHz, Chloroform-d) δ -0.54, -1.18, -1.92, - 3.06, -4.17. HPLC-MS (Condition A): rt= 4.25 min; m / z:1219 [M+1]+.

[0345] rac-1,2,3,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-4-O-Propyl-myo-inositol (IV_A-19): According to general phosphorylation Procedure H, from 66 mg of (III_A-19), 20 mg of (IV_A-19) were obtained (6% yield).31P NMR (162 MHz, Chloroform-d) -0.59, -1.24, - 1.92, -3.01, -4.14. HPLC-MS (Condition A): rt= 3.98 min; m / z: 1133 [M+1]+.

[0346] rac-4-O-(3-(4-(2-(Benzyloxycarbonyl)ethyl)-1H-1,2,3-triazol-1-yl)propyl)- 1,2,3,5,6-pentakis-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)- myo-inositol (IV_A-20): According to general phosphorylation Procedure H, from 34 mg of (III_A-20), 14 mg of (IV_A-20) were obtained (14% yield).31P NMR (162 MHz, Chloroform-d) δ -0.63, -1.61 (d, J = 6.2 Hz), -2.97, -3.98. HPLC-MS (Condition A): rt= 4.16 min; m / z: 1363 [M+1]+.

[0347] rac-4-O-(6-(4-(Methoxycarbonyl)-1H-1,2,3-triazol-1-yl)hexyl)-1,2,3,5,6- pentakis-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-21): According to general phosphorylation Procedure H, from 40 mg of (III_A- 21), 15 mg of (IV_A-21) were obtained (11% yield).31P NMR (162 MHz, Chloroform- d) δ -0.95, -1.45, -1.78, -3.04, -4.12. HPLC-MS (Condition A): rt= 4.00 min; m / z: 1300[M+1]+.

[0348] 1,2,3,4,6-pentakis-O-(3-Oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin- 3-yl)-5-O-Propyl-myo-inositol (IV_C-1): According to general phosphorylation Procedure H, from 15 mg of (III_C-1), 10 mg of (IV_C-1) were obtained (13% yield).31P NMR (162 MHz, Chloroform-d) δ -0.16, -3.40, -3.90. HPLC-MS (Condition A): rt= 4.04 min; m / z: 1133 [M+1]+.

[0349] 5-O-(2-Cyclopropylethyl)-1,2,3,4,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_C-2): According to general phosphorylation Procedure H, from 15 mg of (III_C-2), 10 mg of (IV_C-2) were obtained (14% yield).31P NMR (162 MHz, Chloroform-d) δ -0.21, -3.36, -3.90. HPLC- MS (Condition A): rt= 4.17 min; m / z: 1160 [M+1]+.

[0350] 5-O-(9-Methoxynonyl)-1,2,3,4,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_C-3): According to general phosphorylation Procedure H, from 27 mg of (III_C-3), 15 mg of (IV_C-3) were obtained (15% yield).31P NMR (162 MHz, Chloroform-d) δ -0.07, -3.35, -3.92. HPLC- MS (Condition A): rt= 4.55 min; m / z: 1248 [M+1]+.

[0351] rac-2,3,4,5,6-pentakis-O-(3-Oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-1-O-propyl-myo-inositol (IV_D-1): According to general phosphorylation Procedure H, from 61 mg of (III_D-1), 53 mg of (IV_D-1) were obtained (17% yield).31P NMR (162 MHz, Chloroform-d) δ -1.76, -2.59, -3.97, -4.47, -4.69. HPLC-MS (Condition A): rt= 4.10 min; m / z: 1133 [M+1]+.

[0352] rac-4-O-(6-Amino-6-oxohexyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_A-22) : According to general phosphorylation Procedure H, from 130 mg of (III_A-22), 6 mg of (IV_A-22) were obtained (1% yield).31P NMR (162 MHz, Chloroform-d) δ -1.64, -1.81, -2.31, - 2.89, -4.09. HPLC-MS (Condition A): rt= 3.44 min; m / z: 1205 [M+1]+.

[0353] 1,3,4,5,6-pentakis-O-(3-Oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin- 3-yl)-2-O-propargyl-myo-inositol (IV_B-6): According to general phosphorylation Procedure H, from 54 mg of (III_B-13), 10 mg of (IV_B-6) were obtained (3.6% yield).31P NMR (162 MHz, Chloroform-d) δ -2.03, -4.28, -4.89. HPLC-MS (Condition A): rt= 3.98 min; m / z: 1129 [M+1]+.

[0354] 2-O-(5-(Benzyloxy)pentyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-7): According to general phosphorylation Procedure H, from 67 mg of (III_B-7), 75 mg of (IV_B-7) were obtained (32% yield).31P NMR (162 MHz, Chloroform-d) δ -1.06, -4.00, -4.63. HPLC- MS (Condition A): rt= 4.43 min; m / z: 1267 [M+1]+.

[0355] 2-O-(6,6,6-Trifluorohexyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-8): According to general phosphorylation Procedure R, from 54 mg of (III_B-8), 56 mg of (IV_B-8) were obtained (27% yield).31P NMR (162 MHz, Chloroform-d) δ δ -0.76, -3.76, -4.57. HPLC- MS (Condition A): rt= 4.37 min; m / z: 1229 [M+1]+.

[0356] 2-O-(6-Amino-6-oxohexyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-9): According to general phosphorylation Procedure R, from 46 mg of (III_B-9), 23 mg of (IV_B-9) were obtained (14% yield).31P NMR (162 MHz, Chloroform-d) δ -0.71, -4.15, -4.34. HPLC- MS (Condition A): rt= 3.77 min; m / z: 1204 [M+1]+.

[0357] 2-O-(2-Cyclopentylethyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-10): According to general phosphorylation Procedure R, from 121 mg of (III_B-10), 124 mg of (IV_B-10) were obtained (24% yield).31P NMR (162 MHz, Chloroform-d) δ -1.09, -4.00, -4.64. HPLC-MS (Condition A): rt= 4.40 min; m / z: 1187 [M+1]+.

[0358] 2-O-(2-Cyclopropylethyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-11): According to general phosphorylation Procedure H, from 62 mg of (III_B-11), 85 mg of (IV_B-11) were obtained (29% yield).31P NMR (162 MHz, Chloroform-d) δ -1.30, -3.99, -4.70. HPLC-MS (Condition A): rt= 4.15 min; m / z: 1159 [M+1]+.

[0359] 2-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-1,3,4,5,6-pentakis- O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B- 12): According to general phosphorylation Procedure G, from 65 mg of (III_B-14), 25 mg of (IV_B-12) were obtained (11% yield).31P NMR (162 MHz, Chloroform-d) δ -0.64, -3.84, -4.44. HPLC-MS (Condition A): rt= 3.92 min; m / z: 1272 [M+1]+.

[0360] 2-O-(5-Acetamidopentyl)-1,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-13): According to general phosphorylation Procedure H, from 30 mg of (III_B-15), 10 mg of (IV_B-13) were obtained (8% yield).31P NMR (162 MHz, Chloroform-d) δ -0.61, -4.30 (d, J = 3.6 Hz). HPLC-MS (Condition A): rt= 3.73 min; m / z: 1218 [M+1]+.

[0361] 2-O-((1-(2-(Metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-1,3,4,5,6- pentakis-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_B-14): According to general phosphorylation Procedure G, from 118 mg of (III_B- 16), 101 mg of (IV_B-14) were obtained (24% yield).31P NMR (162 MHz, Chloroform- d) δ -1.44, -4.02, -4.58. HPLC-MS (Condition A): rt= 3.84 min; m / z: 1258 [M+1]+.

[0362] 5-O-(5-Methoxypentyl)-1,2,3,4,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_C-4): According to general phosphorylation Procedure H, from 23 mg of (III_C-4), 6 mg of (IV_C-4) were obtained (6% yield).31P NMR (162 MHz, Chloroform-d) δ -0.06, -3.39, -3.90. HPLC- MS (Condition A): rt= 4.03 min; m / z: 1192 [M+1]+.

[0363] 5-O-(6,6,6-Trifluorohexyl)-1,2,3,4,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_C-5): According to general phosphorylation Procedure H, from 28 mg of (III_C-5), 10 mg of (IV_C-5) were obtained (9% yield).31P NMR (162 MHz, Chloroform-d) δ -0.11, -3.21, -3.83. HPLC- MS (Condition A): rt= 4.34 min; m / z: 1230 [M+1]+.

[0364] 5-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-1,2,3,4,6-pentakis- O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_C- 6): According to general phosphorylation Procedure H, from 15 mg of (III_C-6), 7 mg of (IV_C-6) were obtained (13% yield).31P NMR (162 MHz, Chloroform-d) δ -0.50, -2.93, -3.74. HPLC-MS (Condition A): rt= 3.84 min; m / z: 1273 [M+1]+.

[0365] rac-1-O-(9-Methoxynonyl)-2,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_D-2): According to general phosphorylation Procedure H, from 113 mg of (III_D-2), 100 mg of (IV_D-2) were obtained (24% yield).31P NMR (162 MHz, Chloroform-d) δ -1.97, -2.60, -4.01, - 4.49, -4.61. HPLC-MS (Condition A): rt= 4.40 min; m / z: 1248 [M+1]+.

[0366] rac-1-O-(2-Cyclopropylethyl)-2,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_D-3): According to general phosphorylation Procedure H, from 96 mg of (III_D-3), 90 mg of (IV_D-3) were obtained (20% yield).31P NMR (162 MHz, Chloroform-d) δ -2.28, -2.56, -4.03, -4.49, - 4.58. HPLC-MS (Condition A): rt= 4.08 min; m / z: 1160 [M+1]+.

[0367] rac-1-O-(5-Acetamidopentyl)-2,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_D-4): According to general phosphorylation Procedure G, from 59 mg of (III_D-4), 10 mg of (IV_D-4) were obtained (4% yield).31P NMR (162 MHz, Chloroform-d) δ -2.18, -2.69, -3.76, -4.30, - 4.54. HPLC-MS (Condition A): rt= 3.71 min; m / z: 1219 [M+1]+.

[0368] rac-1-O-(6,6,6-Trifluorohexyl)-2,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)- myo-inositol (IV_D-5): According to general phosphorylation Procedure H, from 64 mg of (III_D-5), 25 mg of (IV_D-5) were obtained (10% yield).31P NMR (162 MHz, Chloroform-d) δ -1.90, -2.58, -3.97, -4.46, - 4.64. HPLC-MS (Condition A): rt= 4.28 min; m / z: 1230 [M+1]+.

[0369] rac-1-O-(2-Cyclopentylethyl)-2,3,4,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_D-6): According to general phosphorylation Procedure H, from 71 mg of (III_D-6), 25 mg of (IV_D-6) were obtained (8% yield).31P NMR (162 MHz, Chloroform-d) δ -1.94, -2.49, -4.12, -4.50, - 4.71. HPLC-MS (Condition A): rt= 4.35 min; m / z: 1188 [M+1]+.

[0370] rac-1-O-((1-(2-(Metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)- 2,3,4,5,6-pentakis-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)- myo-inositol (IV_D-7): According to general phosphorylation Procedure G, from 130 mg of (III_D-7), 104 mg of (IV_D-7) were obtained (22% yield).31P NMR (162 MHz, Chloroform-d) δ -2.38, -2.62, -3.63, -4.36, -4.50. HPLC-MS (Condition A): rt= 3.89 min; m / z: 1259 [M+1]+.

[0371] rac-1-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-2,3,4,5,6- pentakis-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (IV_D-8): According to general phosphorylation Procedure H, from 46 mg of (III_D-8), 10 mg of (IV_D-8) were obtained (6% yield).31P NMR (162 MHz, Chloroform-d) δ - 2.06, -2.65, -3.84, -4.36, -4.59. HPLC-MS (Condition A): rt= 3.86 min; m / z: 1273 [M+1]+. C.4. Intermediates V_A, V_B, V_C and V_D

[0372] rac-4-O-(3-Azidopropyl)-2-O-tert-butyldimethylsilyl-1,3,5-O-methylidyne- myo-inositol (V_A-1): According to general alkylation Procedure A, from 613 mg (2.1 eq.) of (18), 85 mg of (V_A-1) were obtained (19%). HPLC-MS (Condition B): rt= 3.15 min; m / z: 388 [M+1]+.

[0373] rac-4-O-(6-Azidohexyl)-2-O-tert-butyldimethylsilyl-1,3,5-O-methylidyne- myo-inositol (V_A-2): According to general alkylation Procedure A, from 391 mg (2 eq.) of (22), 36 mg of (V_A-2) were obtained (13%). HPLC-MS (Condition B): rt= 4.83 min; m / z: 430 [M+1]+.

[0374] 2-O-(5-Azidopentyl)-4,6-bis-O-(4-methoxybenzyl)-1,3,5-O-methylidyne-myo- inositol (V_B-1): According to general alkylation Procedure A, from 236 mg of (3) and 311 mg (2 eq) of (37), 225 mg of (V_B-1) were obtained (76% yield). HPLC-MS (Condition A): rt= 4.55 min; m / z: 542 [M+1]+.

[0375] 5-O-(5-Azidopentyl)-1,2,3,4,6-penta-O-benzyl-myo-inositol (V_C-1): According to general alkylation Procedure A, from 200 mg of (33) and 180 mg (2 eq) of (37), 218 mg of (V_C-1) were obtained (93% yield). HPLC-MS (Condition A): rt= 6.30 min; m / z: 765 [M+23]+.

[0376] rac-1-O-(5-Azidopentyl)-2,4,6-tri-O-benzyl-3,5-O-ethylidene-myo-inositol (V_D-1): According to general alkylation Procedure B, from 285 mg of (34) and 254 mg (1.5 eq) of (37), 351mg mg of (V_D-1) were obtained (>99% yield). HPLC-MS (Condition A): rt= 5.55 min; m / z: 610 [M+23]+. C.5. Intermediates VI_A

[0377] rac-4-O-(3-Azidopropyl)-myo-inositol (VI_A-1): According to general Hydrolysis Procedure S, from 166 mg of (V_A-1), 110 mg of (VI_A-1) were obtained (97%). HPLC-MS (Condition A): rt= 2.59 min; m / z: 265 [M+1]+.

[0378] rac-4-O-(6-Azidohexyl)-myo-inositol (VI_A-2): According to general Hydrolysis Procedure S, from 279 mg of (V_A-2), 160 mg of (VI_A-2) were obtained (81%). HPLC-MS (Condition A): rt= 2.59 min; m / z: 306 [M+1]+. C.6. Intermediates VII_A

[0379] rac-4-O-(3-Azidopropyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (VII_A-1): According to general phosphorylation Procedure H, from 55 mg of (VI_A-1), 15 mg of (VII_A-2) were obtained (6% yield).31P NMR (162 MHz, Chloroform-d) δ -0.38, -1.11, -1.80, -3.06, - 4.12. HPLC-MS (Condition A): rt= 4.11 min; m / z: 1174 [M+1]+.

[0380] rac-4-O-(3-Azidopropyl)-1,2,3,5,6-pentakis-O-(3-oxido-1,5- dihydrobenzo[e][1,3,2]dioxaphosphepin-3-yl)-myo-inositol (VII_A-2): According to general phosphorylation Procedure H, from 40 mg of (VI_A-1), 44 mg of (VII_A-2) were obtained (28% yield).31P NMR (162 MHz, Chloroform-d) δ -0.63, -1.25, -1.88, -3.02, - 4.14. HPLC-MS (Condition A): rt= 4.31 min; m / z: 1216 [M+1]+. C.7. Intermediates VIII_B and VIII-B’

[0381] 2-O-(19-Methoxynonadecyl)-1,3,5-O-methylidyne-myo-inositol (VIII_B-1): According to general debenzylation Procedure K, from 504 mg of (II_B’-1), 337 mg of (VIII_B-1) were obtained (91% yield).1H NMR (400 MHz, Chloroform-d) δ 5.50 (d, J = 1.3 Hz, 1H), 4.58 (t, J = 3.9 Hz, 2H), 4.32 (br, 2H), 4.27 (br, 1H), 3.82 (br, 1H), 3.62 (t, J = 6.8 Hz, 2H), 3.35 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 1.67 (p, J = 7.2 Hz, 2H), 1.54 (p, J = 7.2 Hz, 2H), 1.38-1.18 (s, 50H).

[0382] 2-O-(29-Methoxynonacosyl)-1,3,5-O-methylidyne-myo-inositol (VIII_B-2): According to general debenzylation Procedure K, from 776 mg of (II_B’-2), 282 mg of (VIII_B-2) were obtained (46% yield).1H NMR (400 MHz, Chloroform-d) δ 5.49 (d, J = 1.3 Hz, 1H), 4.57 (t, J = 4.0 Hz, 2H), 4.32 (dt, J = 4.7, 1.7 Hz, 2H), 4.26 (br, 1H), 3.82 (d, J = 1.7 Hz, 1H), 3.61 (t, J = 6.8 Hz, 2H), 3.35 (t, J = 6.8 Hz, 2H), 3.31 (s, 3H), 1.65 (q, J = 8.7, 7.0 Hz, 2H), 1.54 (p, J = 6.8 Hz, 2H), 1.38-1.18 (s, 59H).

[0383] 4,6-di-O-Benzyl-2-O-(6,6,6-trifluorohexyl)-myo-inositol (VIII_B’-1): According to general hydrolysis Procedure S, from 90 mg of (II_B’-3), 85 mg of (VIII_B’-1) were obtained (96% yield). HPLC-MS (Condition A): rt= 4.19 min; m / z: 521 [M+23]+.

[0384] 2-O-(6-Amino-6-oxohexyl)-4,6-di-O-benzyl-myo-inositol (VIII_B’-2): According to general hydrolysis Procedure S, from 70 mg of (II_B’-4), 68 mg of (VIII_B’-2) were obtained (>99% yield). HPLC-MS (Condition A): rt= 3.19 min; m / z: 474 [M+1]+.

[0385] 4,6-di-O-Benzyl-2-O-(2-cyclopentylethyl)-myo-inositol (VIII_B’-3): According to general hydrolysis Procedure S, from 185 mg of (II_B’-5), 180 mg of (VIII_B’-3) were obtained (>99% yield). HPLC-MS (Condition A): rt= 4.43 min; m / z: 457 [M+1]+, 479 [M+23]+.

[0386] 4,6-di-O-Benzyl-2-O-(2-cyclopropylethyl)-myo-inositol (VIII_B’-4): According to general hydrolysis Procedure S, from 237 mg of (II_B’-6), 230 mg of (VIII_B’-4) were obtained (>99% yield). HPLC-MS (Condition A): rt= 4.43 min; m / z: 451 [M+23]+. C.8. Intermediates IX_D

[0387] rac-2,4,6-tri-O-Benzyl-1-O-propyl-myo-inositol (IX_D-1): According to general hydrolysis Procedure S, from 68 mg of (II_D-1), 63 mg of (IX_D-1) were obtained (98%). HPLC-MS (Condition A): rt= 4.36 min; m / z: 511 [M+23]+.

[0388] rac-2,4,6-tri-O-Benzyl-1-O-(9-methoxynonyl)-myo-inositol (IX_D-2): According to general hydrolysis Procedure S, from 306 mg of (II_D-2), 198 mg of (IX_D- 2) were obtained (68%). HPLC-MS (Condition A): rt= 5.29 min; m / z: 607 [M+1]+, 629 [M+23]+.

[0389] rac-2,4,6-tri-O-Benzyl-1-O-(2-cyclopropylethyl)-myo-inositol (IX_D-3): According to general hydrolysis Procedure S, from 255 mg of (II_D-3), 181 mg of (IX_D- 3) were obtained (74%). HPLC-MS (Condition A): rt= 4.77 min; m / z: 519 [M+1]+.

[0390] rac-1-O-(5-Aminopentyl)-2,4,6-tri-O-benzyl-myo-inositol (IX_D-4): According to general azide reduction Procedure P, from 262 mg of (X_D-1), 198 mg of (IX_D-4) were obtained (79%). HPLC-MS (Condition A): rt= 3.16 min; m / z: 536 [M+1]+.

[0391] rac-2,4,6-tri-O-Benzyl-1-O-(6,6,6-trifluorohexyl)-myo-inositol (IX_D-5): According to general hydrolysis Procedure S, from 107 mg of (II_D-5), 102 mg of (IX_D- 5) were obtained (>99%). HPLC-MS (Condition A): rt= 4.89 min; m / z: 589 [M+1]+.

[0392] rac-2,4,6-tri-O-Benzyl-1-O-(2-cyclopentylethyl)-myo-inositol (IX_D-6): According to general hydrolysis Procedure S, from 124 mg of (II_D-6), 118 mg of (IX_D- 6) were obtained (>99%). HPLC-MS (Condition A): rt= 5.28 min; m / z: 548 [M+1]+.

[0393] rac-1-O-(5-Acetamidopentyl)-2,4,6-tri-O-benzyl-myo-inositol (IX_D-7): According to general amide formation Procedure Q, from 112 mg of (IX_D-4) and 36 mg (1.1 eq.) of 2,5-dioxopyrrolidin-1-yl acetate, 107 mg of (IX_D-7) were obtained (89%). HPLC-MS (Condition A): rt= 3.82 min; m / z: 579 [M+1]+.

[0394] rac-2,4,6-tri-O-Benzyl-1-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1- yl)pentyl)-myo-inositol (IX_D-8): According to general click reaction Procedure M, from 226 mg of (X_D-1) and 56 mg (2 eq.) of 3-methoxyprop-1-yne, 254 mg of (IX_D- 8) were obtained (>99%). HPLC-MS (Condition A): rt= 4.01 min; m / z: 633 [M+1]+.

[0395] rac-2,4,6-tri-O-Benzyl-2-O-propargyl-myo-inositol (IX_D-9): According to general hydrolysis Procedure S, from 164 mg of (II_D-4), 120 mg of (IX_D-9) were obtained (77%). HPLC-MS (Condition A): rt= 4.24 min; m / z: 489 [M+1]+.

[0396] rac-2,4,6-tri-O-Benzyl-1-O-((1-(2-(metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4- yl)methyl)-myo-inositol (IX_D-10): According to general click reaction Procedure L, from 185 mg of (IX_D-9) and 54 mg (1.1 eq.) of (38), 234 mg of (IX_D-10) were obtained (>99%). HPLC-MS (Condition A): rt= 3.88 min; m / z: 618 [M+1]+. C.9 Intermediates X_D

[0397] rac-1-O-(5-Azidopentyl)-2,4,6-tri-O-benzyl-myo-inositol (X_D-1): According to general hydrolysis Procedure S, from 394 mg of (V_D-1), 263 mg of (X_D-1) were obtained (70%). HPLC-MS (Condition A): rt= 4.74 min; m / z: 585 [M+23]+. D. Compound characterization: analytical and spectroscopic tests D.1. NMR

[0398] NMR spectra were recorded on an Agilent VNMRS-400 (1H at 400.10 MHz and31P at 162 MHz). In1H-NMR chemical shifts were expressed in ppm relative to TMS and coupling constant (J) in Hz. In31P NMR no internal standard was used to collect the phosphorous NMR spectra. The usual internal standard is phosphoric acid, but this was not used due to concerns that it would affect the1H-NMR. D.2. HPLC-MS

[0399] Condition A: High-performance Liquid Chromatography (HPLC) 2795 Alliance Waters Aquity coupled to Detector DAD Agilent 1100 and Detector MS Waters ESI triple cuadrupolo Quattro micro, 10 μL of sample in MeOH was injected. Mass spectroscopy (MS) analyzed by FIA (flux injected analysis) coupled to LCT Premier Orthogonal Accelerated Time of Flight Mass Spectrometer, acquiring data by electrospray ionization (ESI) in positive mode. Spectra have been scanned between 50 and 1500 Da with values every 0.2 seconds and peaks are given m / z (% of basis peak). Stationary phase: ZORBAX Extend-C183.5 µm 2.1 x 50 mm (Tª 35ºC). Table 2: Condition A, mobile phase Table 3: Condition A, gradient

[0400] Condition B: HPLC-MS were performed with a High-Performance Liquid Chromatography Thermo Ultimate 3000SD (Thermo Scientific Dionex) coupled to a photodiode array detector and a mass spectrometer LTQ XL ESI-ion trap (Thermo Scientific); 5 μL-20 μL of sample MeOH were injected (c=0.5 mg / mL). Data from mass spectra were analyzed by electrospray ionization in positive and negative mode and peaks are given m / z (% of basis peak). Stationary phase: ZORBAX Extend-C183.5 µm 2.1 x 50 mm (Tª 35ºC). Table 4: Condition B, mobile phase Table 5: Condition B, gradient

[0401] Condition C: HPLC-MS were performed with a High-Performance Liquid Chromatography Thermo Ultimate 3000SD (Thermo Scientific Dionex) coupled to a photodiode array detector and a mass spectrometer LTQ XL ESI-ion trap (Thermo Scientific); 5 μL-20 μL of sample MeOH were injected (c=0.5 mg / mL). Data from mass spectra were analyzed by electrospray ionization in positive and negative mode and peaks are given m / z (% of basis peak). Stationary phase: Xbridge BEH Amide 2.5 µm 4.6 x 150 mm XP. Table 6: Condition C, Mobile phase Table 7: Condition C, gradient

[0402] Condition D: HPLC-MS were performed with a High-Performance Liquid Chromatography Thermo Ultimate 3000SD (Thermo Scientific Dionex) coupled to a photodiode array detector and a mass spectrometer LTQ XL ESI-ion trap (Thermo Scientific); 5 μL-20 μL of sample MeOH were injected (c=0.5 mg / mL). Data from mass spectra were analyzed by electrospray ionization in positive and negative mode and peaks are given m / z (% of basis peak). Stationary phase: ZORBAX Extend-C183.5 µm 2.1 x 50 mm (Tª 35ºC). Table 8: Condition D, mobile phase Table 9: Condition D, gradient

[0403] Condition E: HPLC-MS were performed with a High-Performance Liquid Chromatography Thermo Ultimate 3000SD (Thermo Scientific Dionex) coupled to a photodiode array detector and a mass spectrometer LTQ XL ESI-ion trap (Thermo Scientific); 5 μL-20 μL of sample water were injected (c=0.5 mg / mL). Data from mass spectra were analyzed by electrospray ionization in positive and negative mode and peaks are given m / z (% of basis peak). Stationary phase: Atlantis Premier BEH C18 AX 2.5 µm 2.1x100 mm, SN 1013130715504. Table 10: Condition E, mobile phase Table 11: Condition E, gradient

[0404] Condition F: HPLC-MS were performed with a High-Performance Liquid Chromatography Thermo Ultimate 3000SD (Thermo Scientific Dionex) coupled to a photodiode array detector and a mass spectrometer LTQ XL ESI-ion trap (Thermo Scientific); 5 μL-20 μL of sample water were injected (c=0.5 mg / mL). Data from mass spectra were analyzed by electrospray ionization in positive and negative mode and peaks are given m / z (% of basis peak). Stationary phase: CORTECS T32.7 µm 2.1x150 mm, SN 1353131615509. Table 12: Condition F, mobile phase Table 13: Condition E, gradient Compound 1 rac-4-O-Pentyl-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0405] According to general phosphate deprotection Procedure I, from 64 mg of (IV_A- 1), 14.9 mg of Compound 1 (I_A-1) were obtained (31% yield).1H NMR (400 MHz, D2O) δ 4.99-4.91(m, 1H), 4.42 (q, J = 9.6 Hz, 1H), 4.15–3.95 (m, 3H), 3.88-3.81 (m, 1H), 3.79-3.71 (m, 2H), 3.64 (m, 3H), 1.65 (p, 7.2 Hz, 2H), 1.35-1.29 (m, 4H), 0.88 (m, 7.2 Hz, 3H).31P NMR (162 MHz, D2O) δ 3.94, 3.26. HPLC-MS (Condition C): rt= 10.02 min; m / z: 797 [M+1+DEA]+, 870 [M+1+2DEA]+. Compound 2 rac-4-O-(5-Hydroxypentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0406] According to general phosphate deprotection Procedure I, from 30 mg of (IV_A- 2), 8.24 mg of Compound 2 (I_A-2) were obtained (39% yield).1H NMR (400 MHz, D2O) δ 5.10-5.01 (m, 1H), 4.50–4.39 (m, 1H), 4.18-4.01 (m, 3H), 3.92-3.85 (m, 1H), 3.81-3.71 (m, 2H), 3.61 (t, J = 6.8 Hz, 2H), 1.70-1.63 (m, 2H), 1.62-1.55 (m, 2H), 1.45– 1.38 (m, 2H).31P NMR (162 MHz, D2O) δ 4.76, 2.86, 2.54, -0.16. HPLC-MS (Condition C): rt= 10.36 min; m / z: 813 [M+1+DEA]+, 886 [M+1+2DEA]+. Compound 3 rac-4-O-(5-Methoxypentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0407] According to general phosphate deprotection Procedure I, from 97 mg of (IV_A- 3), 20.5 mg Compound 3 (I_A-3) were obtained (28% yield).1H NMR (400 MHz, D2O) δ 5.00-4.96 (m, 1H), 4.52-4.42 (m, 1H), 4.23-4.61 (m, 3H), 3.86–3.72 (m, 3H), 3.51 (t, J = 6.8 Hz, 2H), 3.35 (s, 3H), 1.70-1.60 (m, 4H), 1.41-1.34 (m, 2H). HPLC-MS (Condition C): rt=10.13 min; m / z: 827 [M+1+DEA]+, 900 [M+1+2DEA]+. Compound 4 rac-4-O-(5-Carboxypentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) undecasodium salt

[0408] According to general phosphate deprotection Procedure J, from 23 mg of (IV_A- 4), 4.4 mg of Compound 4 (I_A-4) were obtained (25% yield).1H NMR (400 MHz, D2O) δ: 5.08 (s, 1H), 5.51-4.43 (m, 1H), 4.25 – 3.97 (m, 3H), 3.86-3.72 (m, 4H), 2.20 (t, J = 7.6 Hz, 2H), 1.71-1.64 (m, 2H), 1.562-1.55 (m, 2H), 1.36-1-32 (m, 2H). HPLC-MS (Condition C): rt=10.46 min; m / z: 841 [M+1+DEA]+, 914 [M+1+2DEA]+. Compound 5 rac-4-O-(2-(4-Acetylpiperazin-1-yl)ethyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0409] According to general phosphate deprotection Procedure I, from 31 mg of (IV_A- 5), 2.8 mg of Compound 5 (I_A-5) were obtained (12% yield).1H NMR (400 MHz, D2O) δ 4.93-4.86 (m, 1H), 4.45 (q, J = 9.6Hz, 1H), 4.28-4.20 (m, 2H), 4.18–4.11(m, 4H), 4.06 (q, J = 9.6Hz, 2H), 4.01-3.88 (m, 2H), 3.88 (t, J = 9.6 Hz, 2H), 3.44-3.29 (m, 4H), 2.18 (s, 3H). HPLC-MS (Condition C): rt=10.28 min; m / z: 808 [M+1+DEA]+, 881 [M+1+2DEA]+, 954[M+1+3DEA]+. Compound 6 2-O-Pentyl-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0410] According to general phosphate deprotection Procedure I, from 325 mg of (IV_B- 1), 88.56 mg of Compound 6 (I_B-1) were obtained (36%yield).1H NMR (400 MHz, D2O) δ 4.36 (m, 3H), 4.08 (q, J = 9.6 Hz, 1H), 4.00 (t, J = 9.6 Hz, 2H), 3.92 (t, J = 7.2 Hz, 2H), 1.63 (p, J = 7.2 Hz, 2H), 1.37-1.30 (m, 4H), 0.96–0.80 (m, 3H).31P NMR (162 MHz, D2O) δ 3.28, 2.32, 1.45. HPLC-MS (Condition C): rt=10.23 min; m / z: 724 [M+1]+, 797 [M+1+DEA]+, 870 [M+1+2DEA]+. Compound 7 2-O-(5-Methoxypentyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0411] According to general phosphate deprotection Procedure I, from 71 mg of (IV_B- 2), 6.7 mg of Compound 7 (I_B-2) were obtained (12.5% yield).1H NMR (400 MHz, D2O) δ 4.38 (q, J = 9.5 Hz, 2H), 4.20 (br, 1H), 4.13-4-05 (m, 3H), 3.90 (t, J = 7.2 Hz, 2H), 3.51 (t, J = 6.8 Hz, 2H), 3.52 (s, 3H), 1.67 (p, J = 7.2 Hz, 2H), 1.62 (p, J = 7.2 Hz, 2H), 1.40 (p, J = 7.2 Hz 2H).31P NMR (162 MHz, D2O) δ 1.66 (br), 1.23 (br). HPLC- MS (Condition C): rt= 10.24 min; m / z: 827 [M+1+DEA]+, 900 [M+1+2DEA]+. Compound 8 2-O-(9-Methoxynonyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0412] According to general phosphate deprotection Procedure I, from 114 mg of (IV_B- 3), 10 mg of Compound 8 (I_B-3) were obtained (11.4% yield).1H NMR (400 MHz, D2O) δ 4.24 (q, J = 8.8 Hz, 2H), 4.02 (s, 1H), 3.95 (t, J = 9.7 Hz, 3H), 3.71 (t, J = 6.8 Hz, 2H), 3.33 (t, J = 6.8 Hz, 2H), 3.18 (s, 3H), 1.48 (t, J = 6.8 Hz, 2H), 1.42 (q, J = 6.8 Hz, 2H), 1.17 (m, 10H).31P NMR (162 MHz, D2O) δ 1.45, 1.24, 0.71. HPLC-MS (Condition D): rt= 0.64 min; m / z: 737 [M+1]+, 810 [M+1+DEA]+, 883 [M+1+2DEA]+. Compound 9 2-O-(19-methoxynonadecyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0413] According to general phosphate deprotection Procedure I, from 35 mg of (IV_B- 4), 13.5 mg of Compound 9 (I_B-4) were obtained (43% yield).1H NMR (400 MHz, D2O) δ 4.20 (q, J = 8.8 Hz, 2H), 4.08 (s, 1H), 3.97–3.83 (m, 3H), 3.73 (t, J = 7.5 Hz, 2H), 3.32 (t, J = 6.7 Hz, 2H), 3.18 (s, 3H), 1.50-1.39 (m, 4H), 1.12 (br, 30H).31P NMR (162 MHz, D2O) δ 2.29, 1.56, 1.37. HPLC-MS (Condition D): rt= 6.90 min; m / z: 1023 [M+1+2DEA]+, 1095 [M+1+3DEA]+. Compound 10 2-O-(29-methoxynonacosyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0414] According to general phosphate deprotection Procedure I, from 18 mg of (IV_B- 5), 5 mg of Compound 10 (I_B-5) were obtained (34% yield).1H NMR (400 MHz, D2O) δ 4.25 (q, J = 9.4 Hz, 2H), 4.03-3.92 (m, 4H), 3.72–3.66 (m, 2H), 3.32 (t, J = 6.7 Hz, 2H), 3.18 (s, 3H), 1.51-1.38 (m, 4H), 1.17–1.11 (m, 50H).31P NMR (162 MHz, D2O) δ 1.47, 0.91, -0.25. Compound 11 rac-4-O-(3-(p-Tolyl)propyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0415] According to general phosphate deprotection Procedure I, from 44 mg of (IV_A- 6), 10 mg of Compound 11 (I_A-6) were obtained (30% yield).1H NMR (400 MHz, D2O) δ 7.19 (d, J = 7.8 Hz, 2H), 7.11 (d, J = 7.8 Hz, 2H), 4.43-3.83 (m, 2H), 3.81-3.66 (m, 2H), 2.59 (t, J = 8 Hz, 2H), 2.22 (s, 3H), 1.90-1.78 (m, 2H). HPLC-MS (Condition C): rt= 9.90 min; m / z: 713 [M+1]+, 785 [M+1+DEA]+, 759 [M+1+2DEA]+, 932 [M+1+3DEA]+. Compound 12 rac-4-O-(4-Methylpentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0416] According to general phosphate deprotection Procedure I, from 47 mg of (IV_A- 7), 10.2 mg of Compound 12 (I_A-7) were obtained (30% yield). δ 1H NMR (400 MHz, D2O) δ 4.57-3.85 (m, 6H), 3.71-3.60 (m, 2H), 1.63-1.52 (m, 2H), 1.52-1.43 (m, 1H), 1.13-1.07 (m, 2H), 0.79 (d, J = 6.6 Hz, 6H). HPLC-MS (Condition E): rt= 10.13 min; m / z: 665 [M+1]+, 738 [M+1+DEA]+, 811 [M+1+2DEA]+, 884 [M+1+3DEA]+. Compound 13 rac-4-O-(6,6,6-Trifluorohexyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0417] According to general phosphate deprotection Procedure I, from 48 mg of (IV_A- 8), 3.8 mg of Compound 13 (I_A-8) were obtained (10% yield).1H NMR (400 MHz, D2O) δ 4.58–3.86 (m, 6H), 3.78–3.59 (m, 2H), 2.17–2.05 (m, 2H), 1.60 (p, J = 7.6 Hz, 2H), 1.50 (p, J = 7.6 Hz, 2H), 1.35 (p, J = 7.6 Hz, 2H). HPLC-MS (Condition C): rt= 10.49 min; m / z:865 [M+1+2DEA]+. Compound 14 rac-4-O-(3-(4-Methoxyphenyl)propyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0418] According to general phosphate deprotection Procedure I, from 48 mg of (IV_A- 9), 4.1 mg of Compound 14 (I_A-9) were obtained (11% yield).1H NMR (400 MHz, D2O) δ 7.23 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.46-3.80 (m, 6H), 3.79-3.68 (m, 2H), 2.58 (t, J = 8.0 Hz, 2H), 1.85 (p, J = 8.0 Hz, 2H). HPLC-MS (Condition C): rt= 10.11 min; m / z: 729 [M+1]+, 802 [M+1+DEA]+, 875 [M+1+2DEA]+. Compound 15 rac-4-O-(3-(3-(Trifluoromethyl)phenyl)propyl)-myo-inositol-1,2,3,5,6- pentakis(phosphate) decasodium salt

[0419] According to general phosphate deprotection Procedure I, from 35 mg of (IV_A- 10), 8.6 mg of Compound 15 (I_A-10) were obtained (32% yield).1H NMR (400 MHz, D2O) δ 7.59 (s, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 4.50–3.89 (m, 5H), 3.87–3.72 (m, 3H), 2.71 (t, J = 8.0 Hz, 2H), 1.95-1.83 (m, 2H). HPLC-MS (Condition C): rt= 9.55 min; m / z: 767 [M+1]+, 840 [M+1+DEA]+, 913 [M+1+2DEA]+. Compound 16 rac-4-O-(2-Cyclopentylethyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0420] According to general phosphate deprotection Procedure I, from 33 mg of (IV_A- 11), 6.6 mg of Compound 16 (I_A-11) were obtained 26% yield).1H NMR (400 MHz, D2O) δ 4.49–3.81 (m, 6H), 3.79–3.61 (m, 2H), 1.73-1.64 (m, 2H), 1.63–1.55 (m, 2H), 1.52-1.45 (m, 2H), 1.43-1.36 (m, 2H), 1.22-1.16 (m, 1H), 1.14-099 (m, 2H). HPLC-MS (Condition C): rt= 10.34 min; m / z: 677 [M+1]+, 823 [M+1+2DEA]+. Compound 17 rac-4-O-(2-Cyclopropylethyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0421] According to general phosphate deprotection Procedure I, from 46 mg of (IV_A- 12), 9.5 mg of Compound 17 (I_A-12) were obtained (27% yield).1H NMR (400 MHz, D2O) δ 4.55–3.84 (m, 6H), 3.77-3.71 (m, 2H), 1.44 (q, J = 7.3 Hz, 2H), 0.74–0.59 (m, 1H), 0.32–0.21 (m, 2H), 0.10–-0.10 (m, 2H). HPLC-MS (Condition C): rt= 10.77 min; m / z: 649 [M+1]+, 795 [M+1+2DEA]+. Compound 18 rac-4-O-(5-(1H-Pyrazol-1-yl)pentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0422] According to general phosphate deprotection Procedure I, from 100 mg of (IV_A- 13), 18.8 mg of Compound 18 (I_A-13) were obtained (25% yield).1H NMR (400 MHz, D2O) δ 7.60 (dd, J = 2.2, 0.8 Hz, 1H), 7.46 (dd, J = 2.2, 0.8 Hz, 1H), 6.24 (t, J = 2.2 Hz, 1H), 4.63–3.89 (m, 6H), 4.08 (t, J = 7.2 Hz, 2H), 3.73–3.56 (m, 2H), 1.76 (p, J = 7.2 Hz, 2H), 1.62–1.51 (m, 2H), 1.18 (p, J = 7.2 Hz, 2H). HPLC-MS (Condition C): rt= 10.13 min; m / z: 717 [M+1]+, 790 [M+1+DEA]+, 863 [M+1+2DEA]+. Compound 19 rac-4-O-(5-Acetamidopentyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0423] According to general phosphate deprotection Procedure I, from 14 mg of (IV_A- 14), 3.1 mg of Compound 19 (I_A-14) were obtained (29% yield).1H NMR (400 MHz, D2O) δ 4.55–3.84 (m, 6H), 3.70-3.47 (m, 2H), 3.09 (t, J = 6.8 Hz, 2H), 1.90 (s, 3H), 1.55- 1.42 (m, 2H), 1.25-1.18 (m, 4H). HPLC-MS (Condition E): rt= 4.88 min; m / z: 781 [M+1+DEA]+, 854 [M+1+2DEA]+. Compound 20 rac-4-O-(10-Carboxyldecyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) undecasodium salt

[0424] According to general phosphate deprotection Procedure J, from 7.5 mg of (IV_A- 15), 3.4 mg of Compound 20 (I_A-15) were obtained (59% yield).1H NMR (400 MHz, D2O) δ 4.58–3.76 (m, 6H), 3.78–3.58 (m, 2H), 2.08 (t, J = 7.6 Hz, 2H), 1.61-1.52 (m, 2H), 1.45 (t, J = 7.6 Hz, 2H), 1.21 (br, 12H). HPLC-MS (Condition E): rt= 5.20 min; m / z: 838 [M+1+DEA]+, 911 [M+1+2DEA]+, 984 [M+1+3DEA]+. Compound 21 rac-4-O-(10-Hydroxydecyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0425] According to general phosphate deprotection Procedure I, from 12.9 mg of (IV_A- 16), 2.8 mg of Compound 21 (I_A-16) were obtained (31% yield).1H NMR (400 MHz, D2O) δ 4.49–3.74 (m, 6H), 3.72-3.63 (m, 2H), 3.51 (t, J = 6.8 Hz, 2H), 1.60-1.53 (m, 2H), 1.45 (t, J = 6.8 Hz, 2H), 1.22 (br, 12H). HPLC-MS (Condition F): rt= 6.27 min; m / z: 810 [M+1+DEA]+, 883 [M+1+2DEA]+. Compound 22 rac-4-O-Methyl-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0426] According to general phosphate deprotection Procedure I, from 10 mg of (IV_A- 17), 0.6 mg of Compound 22 (I_A-17) were obtained (8% yield).1H NMR (400 MHz, D2O) δ 4.49–3.77 (m, 6H), 3.52 (s, 3H). HPLC-MS (Condition E): rt= 2.26 min; m / z: 668 [M+1+DEA]+, 741 [M+1+2DEA]+, 814 [M+1+3DEA]+. Compound 23 rac-4-O-(7-Methoxyheptyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0427] According to general phosphate deprotection Procedure I, from 30 mg of (IV_A- 18), 9.7 mg of Compound 23 (I_A-18) were obtained (42% yield).1H NMR (400 MHz, D2O) δ 4.45–3.79 (m, 5H), 3.77–3.60 (m, 3H), 3.40 (t, J = 6.8 Hz, 2H), 3.26 (s, 3H), 1.66– 1.38 (m, 4H), 1.25 (br, 6H). HPLC-MS (Condition C): rt= 10.98 min; m / z: 855 [M+1+2DEA]+. Compound 24 rac-4-O-Propyl-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0428] According to general phosphate deprotection Procedure I, from 20 mg of (IV_A- 19), 1.5 mg of Compound 24 (I_A-19) were obtained (10% yield).1H NMR (400 MHz, D2O) δ 4.40-3.60 (m, 8H), 1.60,-1-51 (m, 2H), 0.81 (t, J = 7.2 Hz, 3H). HPLC-MS (Condition E): rt= 3.49 min; m / z: 696 [M+1+DEA]+, 769 [M+1+2DEA]+, 842 [M+1+3DEA]+. Compound 25 rac-4-O-(3-(4-(2-carboxyethyl)-1H-1,2,3-triazol-1-yl)propyl)-myo-inositol-1,2,3,5,6- pentakis(phosphate) undecasodium salt

[0429] According to general phosphate deprotection Procedure J, from 14 mg of (IV_A- 20), 3.0 mg of Compound 25 (I_A-20) were obtained (29% yield).1H NMR (400 MHz, D2O) δ 7.81 (s, 1H), 4.53–4.44 (m, 2H), 4.39-3.60 (m, 8H), 2.84 (t, J = 8 Hz, 2H), 2.44 (t, J = 8 Hz, 2H), 2.16-2.05 (m, 2H). HPLC-MS (Condition E): rt= 4.73 min; m / z: 762 [M+1]+, 835 [M+1+DEA]+, 908 [M+1+2DEA]+, 981 [M+1+3DEA]+. Compound 26 rac-4-O-(6-(4-(carboxy)-1H-1,2,3-triazol-1-yl)hexyl)-myo-inositol-1,2,3,5,6- pentakis(phosphate) undecasodium salt

[0430] According to general phosphate deprotection Procedure J, from 15 mg of (IV_A- 21), 1.9 mg of Compound 26 (I_A-21) were obtained (16% yield).1H NMR (400 MHz, D2O) δ 8.13 (s, 1H), 4.35 (t, J = 7.2 Hz, 2H), 4.39–3.43 (m, 8H), 1.88-1.78 (m, 2H), 1.62- 1.54 (m, 2H), 1.36-1.23 (m, 4H). HPLC-MS (Condition E): rt= 4.94 min; m / z: 849 [M+1+DEA]+, 922 [M+1+2DEA]+, 994 [M+1+3DEA]+. Compound 27 rac-4-O-(3-Aminopropyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0431] According to general phosphate deprotection Procedure I, from 15 mg of (VI_A- 1), 1.9 mg of Compound 27 (I_A-22) were obtained (17% yield).1H NMR (400 MHz, D2O) δ 4.40-3.80 (m, 6H), 3.08 (t, J = 6.4 Hz, 2H), 1.94-1.88 (m, 2H). HPLC-MS (Condition E): rt= 1.63 min; m / z: 638 [M+1]+, 711 [M+1+DEA]+, 784 [M+1+2DEA]+. Compound 28 rac-4-O-(6-Aminohexyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0432] According to general phosphate deprotection Procedure I, from 44 mg of (VI_A- 2), 15.6 mg of Compound 28 (I_A-23) were obtained (48% yield).1H NMR (400 MHz, D2O) δ 4.40-3.80 (m, 6H), 3.55-3.65 (m, 2H), 2.92 (dd, J = 7.6, 5.6 Hz, 2H), 1.70-1.40 (m, 4H), 1.28-1.13 (m, 4H). HPLC-MS (Condition C): rt= 9.23 min; m / z: 752 [M+1+DEA]+, 825 [M+1+2DEA]+. Compound 29 5-O-Propyl-myo-inositol-1,2,3,4,6-pentakis(phosphate) decasodium salt

[0433] According to general phosphate deprotection Procedure I, from 10 mg of (IV_C- 1), 3.3 mg of Compound 29 (I_C-1) were obtained (45% yield).1H NMR (400 MHz, D2O) δ 4.64-4.56 (m, 1H), 4.38 (q, J = 9.6 Hz, 2H), 4.02-3.93 (m, 2H), 3.71 (t, J = 7.4 Hz, 2H), 3.34 (t, J = 9.6 Hz, 1H), 1.58 (q, J = 7.4 Hz, 2H), 0.81 (t, J = 7.4 Hz, 3H). HPLC- MS (Condition E): rt= 3.41 min; m / z: 696 [M+1+DEA]+, 769 [M+1+2DEA]+, 842 [M+1+3DEA]+. Compound 30 5-O-(2-Cyclopropylethyl)-myo-inositol-1,2,3,4,6-pentakis(phosphate) decasodium salt

[0434] According to general phosphate deprotection Procedure I, from 10 mg of (IV_C- 2), 3.53 mg of Compound 30 (I_C-2) were obtained (47% yield).1H NMR (400 MHz, D2O) δ 4.36 (q, J = 9.6 Hz, 2H), 3.99-3.91 (m, 2H), 3.81 (t, J = 7.6 Hz, 2H), 3.65-3.55 (m, 1H), 3.36–3.26 (m, 1H), 1.47 (q, J = 7.6 Hz, 2H), 0.70-061 (m, 1H), 0.32–0.26 (m, 2H), 0.01–-0.04 (m, 2H). HPLC-MS (Condition E): rt= 4.96 min; m / z: m / z: 722 [M+1+DEA]+, 795 [M+1+2DEA]+, 868 [M+1+3DEA]+. Compound 31 5-O-(9-Methoxynonyl)-myo-inositol-1,2,3,4,6-pentakis(phosphate) decasodium salt

[0435] According to general phosphate deprotection Procedure I, from 15 mg of (IV_C- 3), 6.7 mg of Compound 31 (I_C-3) were obtained (58% yield).1H NMR (400 MHz, D2O) δ 4.54-4.46 (m, 2H), 4.44-4.15 (m, 3H), 3.84 (br, 1H), 3.66 (t, J = 7.6 Hz, 2H), 3.40 (t, J = 6.8 Hz, 2H), 3.26 (s, 3H), 1.63-1.53 (m, 2H), 1.53-1.43 (m, 2H), 1.23 (br, 10H). HPLC-MS (Condition E): rt= 5.95 min; m / z: m / z: 810 [M+1+DEA]+, 883 [M+1+2DEA]+, 956 [M+1+3DEA]+. Compound 32 rac-1-O-Propyl-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt

[0436] According to general phosphate deprotection Procedure I, from 53 mg of (IV_D- 1), 13.28 mg of Compound 32 (I_D-1) were obtained (34% yield).1H NMR (400 MHz, D2O) δ 4.60–3.80 (m, 6H), 3.70-3.52 (m, 2H),1.66–1.53 (m, 2H), 0.81 (t, J = 7.6 Hz, 3H). HPLC-MS (Condition E): rt= 3.65 min; m / z: 696 [M+1+DEA]+, 769 [M+1+2DEA]+, 842 [M+1+3DEA]+. Compound 33 rac-4-O-(6-Amino-6-oxohexyl)-myo-inositol-1,2,3,5,6-pentakis(phosphate) decasodium salt

[0437] According to general phosphate deprotection Procedure I, from 6 mg of (IV_A- 22), 1.42 mg of Compound 33 (I_A-24) were obtained (31% yield).1H NMR (400 MHz, D2O) δ 4.36 (q, J = 9.2 Hz, 1H), 4.06 (q, J = 9.2 Hz, 1H), 4.00 (d, J = 8.0 Hz, 1H), 3.94 (t, J = 9.2 Hz, 1H), 3.78 (q, J = 8.0 Hz, 1H), 3.72-3.67 (m, 1H) 3.67 (t, J = 6.8 Hz, 2H), 2.21 (t, J = 6.8 Hz, 1H), 1.58 (p, J = 6.8 Hz, 2H), 1.55 (p, J = 6.8 Hz, 2H), 1.32 (p, J = 6.8 Hz, 2H). HPLC-MS (Condition E): rt= 2.25 min; m / z: 694 [M+1]+, 767 [M+1+DEA]+, 840 [M+1+2DEA]+. Compound 34 2-O-Propyl-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0438] According to general phosphate deprotection Procedure I, from 30 mg of (IV_B- 6), 5 mg of Compound 34 (I_B-6) were obtained (23% yield).1H NMR (400 MHz, D2O) δ 4.80-4.70 (m, 1H) 4.55-4.43 (m, 2H), 4.24 (brs, 1H), 4.22-4.13 (m, 2H), 3.84 (t, J = 7.2 Hz, 2H), 1.64 (q, J = 7.2 Hz, 2H), 0.94 (t, J = 7.2 Hz, 3H). HPLC-MS (Condition E): rt= 4.85 min; m / z: 623 [M+1]+, 796 [M+1+DEA]+, 769 [M+1+2DEA]+. Compound 35 2-O-(5-Acetamidopentyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0439] According to general phosphate deprotection Procedure I, from 12 mg of (IV_B- 13), 8 mg of Compound 35 (I_B-7) were obtained (89% yield).1H NMR (400 MHz, D2O) δ 4.80-4.70 (m, 1H), 4.48–4.31 (m, 2H), 4.13–3.87 (m, 5H), 3.86–3.74 (m, 1H), 3.19 (t, J = 6.7 Hz, 2H), 1.99 (s, 3H), 1.72–1.61 (m, 2H), 1.56 (q, J = 7.6 Hz, 2H), 1.46-1.37 (m, 2H). HPLC-MS (Condition E): rt= 4.97 min; m / z: 781 [M+1+DEA]+, 854 [M+1+2DEA]+. Compound 36 2-O-(6,6,6-Trifluorohexyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0440] According to general phosphate deprotection Procedure I, from 58 mg of (IV_B- 8), 8.5 mg of Compound 36 (I_B-8) were obtained (20% yield).1H NMR (400 MHz, D2O) 4.80-4.70 (m, 1H), δ 4.45–4.30 (m, 2H), 4.15-3.86 (m, 4H), 3.86–3.70 (m, 1H), 2.32–2.08 (m, 2H), 1.67 (p, J = 7.6 Hz, 2H), 1.60 (p, J = 7.6 Hz, 2H), 1.47 (p, J = 7.6 Hz, 2H).31P NMR (162 MHz, D2O) δ 3.23, 2.24, 1.51. HPLC-MS (Condition E): rt= 4.85 min; m / z: 719 [M+1]+, 792 [M+1+DEA]+, 865 [M+1+2DEA]+, 938 [M+1+3DEA]+. Compound 37 2-O-(6-Amino-6-oxohexyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0441] According to general phosphate deprotection Procedure I, from 24 mg of (IV_B- 9), 4.2 mg of Compound 37 (I_B-9) were obtained (24% yield).1H NMR (400 MHz, D2O) δ 4.73-4.83 (m, 1H), 4.43-4.31 (m, 2H), 4.15 – 3.99 (m, 3H), 3.96 (m, 2H), 2.31 (t, J = 7.6 Hz, 2H), 1.66 (p, J = 7.4 Hz, 4H), 1.48-1.42 (m, 2H).31P NMR (162 MHz, D2O) δ 2.96, 1.94, 1.39. HPLC-MS (Condition E): rt= 1.77 min; m / z: 694 [M+1]+, 767 [M+1+DEA]+, 840 [M+1+2DEA]+, 913 [M+1+3DEA]+. Compound 38 2-O-(2-Cyclopentylethyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0442] According to general phosphate deprotection Procedure I, from 124 mg of (IV_B- 10), 7.2 mg of Compound 38 (I_B-10) were obtained (7.7% yield).1H NMR (400 MHz, D2O) δ 4.92-4.65 (m, 2H), 4.57–4.28 (m, 2H), 4.18-3.87 (m, 3H), 3.86-3.74 (m, 1H), 1.89-1.74 (m, 3H), 1.73– 1.64 (m, 2H), 1.64–1.53 (m, 2H), 1.53–1.41 (m, 2H), 1.20-1.10 (m, 2H). HPLC-MS (Condition E): rt= 5.16 min; m / z: 677 [M+1]+, 750 [M+1+DEA]+, 823 [M+1+2DEA]+, 896 [M+1+3DEA]+. Compound 39 2-O-(2-Cyclopropylethyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0443] According to general phosphate deprotection Procedure I, from 65 mg of (IV_B- 11), 3.0 mg of Compound 39 (I_B-11) were obtained (4.7% yield).1H NMR (400 MHz, D2O) δ 5.00–4.78 (m, 1H), 4.33–4.15 (m, 2H), 4.05–3.83 (m, 4H), 3.84–3.68 (m, 1H), 1.44 (q, J = 7.2 Hz, 2H), 0.77–0.60 (m, 1H), 0.38–0.25 (m, 2H), 0.07–-0.08 (m, 2H). HPLC-MS (Condition E): rt= 1.94 min; m / z: 649 [M+1]+, 722 [M+1+DEA]+, 795 [M+1+2DEA]+, 868 [M+1+3DEA]+. Compound 40 2-O-(5-Hydroxypentyl)-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0444] According to general phosphate deprotection Procedure I, from 73 mg of (IV_B- 7), 13.6 mg of Compound 40 (I_B-12) were obtained (27% yield).1H NMR (400 MHz, D2O) δ 5.21-4.73 (m, 2H), 4.60-4.17 (m, 2H), 4.40 (q, J = 9.6 Hz, 1H), 4.08 (q, J = 9.6 Hz, 1H), 4.03–3.89 (m, 1H), 3.89 -3.70 (m, 1H), 3.63 (t, J = 6.5 Hz, 2H), 1.75-1.59 (m, 4H), 1.48-144 (m, 2H). HPLC-MS (Condition E): rt= 4.85 min; m / z: 667 [M+1]+. Compound 41 2-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-1,3,4,5,6- pentakis(phosphate) decasodium

[0445] According to general phosphate deprotection Procedure I, from 25 mg of (IV_B- 12), 10.8 mg of Compound 41 (I_B-13) were obtained (56% yield).1H NMR (400 MHz, D2O) δ 8.08 (s, 1H), 4.61 (s, 2H), 4.47 (t, J = 7.2 Hz, 2H), 4.47-4.28 (m, 3H), 4.17-3.87 (m, 4H), 3.39 (s, 3H), 1.97 (p, J = 7.7 Hz, 2H), 1.69 (p, J = 7.7 Hz, 2H), 1.45–1.33 (m, 2H).31P NMR (162 MHz, D2O) δ 3.65, 2.66, 1.67. HPLC-MS (Condition E): rt= 5.33 min; m / z: 907 [M+1+2DEA]+. Compound 42 2-O-((1-(2-Carboxyethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol-1,3,4,5,6- pentakis(phosphate) undecasodium salt

[0446] According to general phosphate deprotection Procedure J, from 100 mg of (IV_B- 14), 45 mg of Compound 42 (I_B-14) were obtained (57% yield).1H NMR (400 MHz, D2O) δ 8.16 (s, 1H), 5.07 (s, 2H), δ 4.73-4.83 (m, 1H), 4.63 (t, J = 7.2 Hz, 3H), 4.32 (brs, 3H), 4.04 (brs, 2H), 2.81 (t, J = 7.2 Hz, 2H). HPLC-MS (Condition E): rt= 1.16 min; m / z: 880 [M+1+2DEA]+, 953 [M+1+3DEA]+. Compound 43 2-O-Propargyl-myo-inositol-1,3,4,5,6-pentakis(phosphate) decasodium salt

[0447] According to general phosphate deprotection Procedure T, from 25 mg of (IV_B- 6), 7.5 mg of Compound 43 (I_B-15) were obtained (40% yield).1H NMR (400 MHz, D2O) δ 4.64 (s, 2H), 4.42-4.34 (m, 3H), 4.14-4.06 (m, 3H), 2.88 (t, J = 2.4 Hz, 1H).31P NMR (162 MHz, D2O) δ 2.89, 1.95, 1.43. HPLC-MS (Condition E): rt= 3.20 min; m / z: 693 [M+1+DEA]+, 766 [M+1+2DEA]+. Compound 44 5-O-(9-Methoxypentyl)-myo-inositol-1,2,3,4,6-pentakis(phosphate) decasodium salt

[0448] According to general phosphate deprotection Procedure I, from 6 mg of (IV_C- 4), 1.7 mg of Compound 44 (I_C-4) were obtained (37% yield).1H NMR (400 MHz, D2O) δ 4.64–4.45 (m, 1H), 4.43-4.35 (m, 1H), 4.32–4.16 (m, 1H), 4.023-3.87 (m, 2H), 3.77-3.70 (m, 2H), 3.66-3.55 (m, 1H), 3.42 (t, J = 6.8 Hz, 2H), 3.26 (s, 3H), 1.65-1.56 (m, 2H), 1.53 (iq, J = 6.8 Hz, 2H), 1.20-1.23 (m, 2H).31P NMR (162 MHz, D2O) δ 3.64, 3.23, 2.63. HPLC-MS (Condition E): rt= 4.67 min; m / z: 826 [M+1+2DEA]+, 899 [M+1+3DEA]+. Compound 45 5-O-(6,6,6-Trifluorohexyl)-myo-inositol-1,2,3,4,6-pentakis(phosphate) decasodium salt

[0449] According to general phosphate deprotection Procedure I, from 10 mg of (IV_C- 5), 1 mg of Compound 45 (I_C-5) were obtained (13% yield).1H NMR (400 MHz, D2O) δ 4.58–4.16 (m, 3H), 4.02–3.90 (m, 2H), 3.80–3.71 (m, 2H), 3.39–3.22 (m, 1H), 2.23– 2.02 (m, 2H), 1.67–1.56 (m, 2H), 1.51 (p, J = 7.4 Hz, 2H), 1.38-1.30 (m, 2H). HPLC-MS (Condition E): rt= 6.12 min; m / z: 865 [M+1+2DEA]+, 938 [M+1+3DEA]+. Compound 46 5-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-1,2,3,4,6- pentakis(phosphate) decasodium salt

[0450] According to general phosphate deprotection Procedure I, from 7 mg of (IV_C- 6), 2.5 mg of Compound 45 (I_C-6) were obtained (46% yield).1H NMR (400 MHz, D2O) δ 7.99 (s, 1H), 4.53 (s, 2H), 4-50-4.35 (m, 1H), 4.37 (t, J = 7.0 Hz, 2H), 4.06–3.84 (m, 3H), 3.78–3.68 (m, 2H), 3.30 (s, 3H), 1.86 (t, J = 7.6 Hz, 2H), 1.69–1.58 (m, 2H), 1.33–1.14 (m, 4H). HPLC-MS (Condition E): rt= 3.20 min; m / z: 762 [M+1]+. Compound 47 rac-1-O-(9-Methoxynonyl)-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt

[0451] According to general phosphate deprotection Procedure I, from 100 mg of (IV_D- 2), 44 mg of Compound 47 (I_D-2) were obtained (57% yield).1H NMR (400 MHz, D2O) δ 4.65–4.39 (m, 4H), 4.29 (d, J = 11.6 Hz, 1H), 4.18-3.94 (m, 1H), 3.85-3.73 (m, 1H), 3.72-3.65 (m, 1H), 3.47 (t, J = 6.6 Hz, 2H), 3.33 (s, 3H), 1.71-1.61 (m, 2H), 1.56 (p, J = 6.6 Hz, 2H), 1.30 (brs, 10H). HPLC-MS (Condition E): rt= 5.45 min; m / z: 810 [M+1+DEA]+, 883 [M+1+2DEA]+. Compound 48 rac-1-O-(2-Cyclopropylethyl)-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt

[0452] According to general phosphate deprotection Procedure I, from 90 mg of (IV_D- 3), 15.4 mg of Compound 48 (I_D-3) were obtained (23% yield).1H NMR (400 MHz, D2O) δ 4.64–4.32 (m, 5H), 4.22-4.09 (m, 1H), 3.78-3.65 (m, 2H), 1.49-1.41 (m, 2H), 0.72-0.59 (m, 1H), 0.34–0.27 (m, 2H), 0.04–-0.04 (m, 2H). HPLC-MS (Condition E): rt= 4.92 min; m / z: 722 [M+1+DEA]+, 795 [M+1+2DEA]+, 868 [M+1+3DEA]+. Compound 49 rac-1-O-(5-Acetamidopentyl)-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt

[0453] According to general phosphate deprotection Procedure I, from 10 mg of (IV_D- 4), 1.7 mg of Compound 49 (I_D-4) were obtained (22% yield).1H NMR (400 MHz, D2O) δ 4.39-4.22 (m, 2H), 4.10-4.00 (m, 1H), 3.97-3.86 (m, 1H), 3.73-3.66 (m, 1H), 3.54- 3.46 (m, 1H), 3.09 (t, J = 6.5 Hz, 2H), 1.90 (s, 3H), 1.62-1.52 (m, 2H), 1.49-1.41 (m, 2H), 1.37-1.29 (m, 2H). HPLC-MS (Condition E): rt= 3.10 min; m / z: 781 [M+1+DEA]+, 854 [M+1+2DEA]+, 926 [M+1+3DEA]+. Compound 50 rac-1-O-(6,6,6-Trifluorohexyl)-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt (CSC-san17-016)

[0454] According to general phosphate deprotection Procedure I, from 23 mg of (IV_D- 5), 0.6 mg of Compound 50 (I_D-5) were obtained (3.4% yield). HPLC-MS (Condition E): rt= 6.83 min; m / z: 719 [M+1]+, 865 [M+1+2DEA]+. Compound 51 rac-1-O-(2-Cyclopentylethyl)-myo-inositol-2,3,4,5,6-pentakis(phosphate) decasodium salt

[0455] According to general phosphate deprotection Procedure I, from 25 mg of (IV_D- 6), 1.6 mg of Compound 51 (I_D-6) were obtained (8.5% yield). HPLC-MS (Condition E): rt= 6.35 min; m / z: 677 [M+1]+, 750 [M+1+DEA]+, 823 [M+1+2DEA]+, 896 [M+1+3DEA]+. Compound 52 rac-1-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-2,3,4,5,6- pentakis(phosphate) decasodium salt

[0456] According to general phosphate deprotection Procedure I, from 10 mg of (IV_D- 8), 6.3 mg of Compound 52 (I_D-7) were obtained (82% yield).1H NMR (400 MHz, D2O) δ 8.07 (s, 1H), 4.61 (s, 2H), 4.51-4.41 (m, 1H), 4.46 (t, J = 7.2 Hz, 2H), 4.36-4.24 (m, 1H), 4.16-3.88 (m, 1H), 3.84-3.52 (m, 3H), 3.39 (s, 3H), 2.00-1.92 (m, 2H), 1.87– 1.61 (m, 2H), 1.48– 1.26 (m, 2H). HPLC-MS (Condition E): rt= 5.19 min; m / z: 835 [M+1+DEA]+, 908 [M+1+2DEA]+. Compound 53 rac-1-O-((1-(2-(Metoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol- 2,3,4,5,6-pentakis(phosphate) undecasodium salt

[0457] According to general phosphate deprotection Procedure J, from 104 mg of (IV_D- 7), 44.1 mg of Compound 53 (I_D-8) were obtained (55% yield).1H NMR (400 MHz, D2O) δ 8.01 (s, 1H), 4.94 (d, J = 12.4 Hz, 1), 4.86 (d, J = 12.4 Hz, 1H), 4.63–4.57 (m, 3H), 4.51-4.33 (m, 2H), 4.31-4.08 (m, 3H), 4.02–3.78 (m, 1H), 2.73 (t, J = 7.1 Hz, 2H). HPLC-MS (Condition E): rt= 1.21 min; m / z: 880 [M+1+2DEA]+, 953 [M+1+3DEA]+. Pharmacological assays Example 1 Pharmacokinetics

[0458] A pharmacokinetic test over IP5 substituted compounds was conducted using an in vivo rat model. The model evaluated the pharmacokinetic profile of Compound 1 (SNF524) when administered intravenously (iv) and subcutaneously (sc).

[0459] An appropriate amount of Compound 1 was weighed to prepare 2 mL of formulations at the doses 5 and 20 mg / kg, considering an injection volume of 2 mL / kg. The vehicle (sterile saline for injection, 0.9% NaCl) was added and the mixture was stirred until a homogenous solution formed by visual inspection. The pH was adjusted with HCl solution (1 / 5, v / v) in the range of 6.4 to 7.7 before adjusting to the final 2 mL volume. The formulations were filtrated (2 mL sterile syringe and PVDF 0.45 μm filter) in a sterile vial for the administration. All formulations were prepared one to three days before the administration, were stored refrigerated (+2 to +8 °C) and protected from light.

[0460] Three male Sprague Dawley (SD) rats (Inotiv, Indianapolis, IN, USA) weighing approximately 205 to 206 g were used for the iv test (Group 1). Three male Sprague Dawley (SD) rats (Inotiv, Indianapolis, IN, USA) weighing approximately 206 to 209 g were used for the sc test (Group 2).

[0461] Animals in Group 1 were administered a dose of 5 mg / kg Compound 1 in 2 mL / kg physiological saline solution (0.9% (w / v) NaCl). The sc administration was made via the intrascapular space.

[0462] Animals in Group 2 were administered a dose of 20 mg / kg Compound 1 in 2 mL / kg physiological saline solution (0.9% (w / v) NaCl). The iv administration was a short 1-minute infusion via the tail vein. Seven blood samples per animal were obtained from the jugular vein (approx.200 µL).

[0463] Plasma samples were obtained using K3EDTA as anticoagulant. Blood samples were kept at 4ºC until and during centrifugation at 3500 rpm (10 minutes). Plasma samples were frozen at -80 ºC until analysis. Samples were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS / MS). Pharmacokinetic analysis was performed by noncompartmental pharmacokinetic analysis using Kinetica v5 software (Alfasoft Ltd., Luton, UK).

[0464] The results showed that Compound 1 had an adequate pharmacokinetic profile when administered either intravenously or subcutaneously. See Tables 14 and 15, plasma pharmacokinetic parameters of Compound 1 in rats after (i) iv administration (5 mg / kg) and (ii) sc administration (20 mg / kg), respectively. Table 14 S t t n A AUCinfCl An max max 1 / 2 points UC0-t ( Vz Vss (ng / ml) (h) (h) [r2] (ng.h / mL) ng.h / (mL / mL) min / k (l / kg) (l / kg) g) 61 0.017 0.081 3 (0.992) 11082 (17.5) 7.45 0.052 0.035 62 123731 0.017 0.101 3 (0.992) 1320 13559 (193) 8 (21.2) 6.13 0.054 0.041 164753 15404 Mean 141858 0.017 0.088 NA 13172 13381 6.33 0.048 0.036 (222) (20.9) SD 20923 (32.7) 0.011 2072 2118 (3.3) 1.04 0.008 0.005 CV% 14.7 12.5 15.7 15.8 16.4 16.9 14.8 Table 15 Mean 32015 ) 0.50 1.09 NA 29317 (50.0 29032 (45.8) 12.0 54.8 SD 2896 (0.25- (4.5) 0.50) 0.48 - 3407 3368 (5.3) 2.3 6.3 CV% 9.0 43.6 - 11.7 11.5 19.22 11.5 Example 2 Treatment of Ectopic Calcification-related Diseases

[0465] The concentration-response efficacy of IP5 substituted compounds for inhibiting the calcification of human vascular smooth muscle cells (hVSMC) was analyzed using an in vitro model. The model evaluated the effects of Compound 47 (SNF733), Compound 48 (SNF734), and Compound 53 (SNF737) on the calcification of cultured hVSMC.

[0466] Compound 47 (SNF733), Compound 48 (SNF734), and Compound 53 (SNF737) were directly resuspended in Milli-Q® water to obtain a final concentration of 20 mM of Compound 47 (SNF733) and Compound 53 (SNF737), and a final concentration of 10 mM of Compound 48 (SNF734). Thereafter, a 2 mL stock at 10 mM of Compound 47 (SNF733) and Compound 48 (SNF734) was prepared. All test items were filtered in the cell culture sterile hood with a 0.22 µM polyethersulfone (PES) filter. Finally, the required dilutions of every test item were prepared in filtered Milli-Q® water. These stock solutions were 100x the final concentration in the culture media. 1. Cell culture and treatments

[0467] VSMC were thawed and seeded in a cell culture flask with SmBM medium supplemented with insulin, hFBG-B, GA-1000, hEGF (Lonza Biosciences, Basel, CH) and 20% fetal bovine serum (FBS). Cells were maintained at 37ºC in a 5% CO2 atmosphere. When the cells reached confluence, they were detached by incubating for 2 min with Trypsin-Versene (EDTA) Mix (1X) after a previous PBS wash. Cells were counted manually using a Neubauer chamber and then seeded in 12-well cell culture plates (10500 cells / cm2, 40000 cells / well) with DMEM standard medium supplemented with 20% FBS, 1 mM sodium pyruvate, 2 mM glutamine, 100 UI / mL penicillin, 100 µg / mL streptomycin, 0.25 µg / mL amphotericin and 16 mM HEPES) and grown until 90% confluence.

[0468] Then, the culture medium was changed to osteogenic medium (DMEM with the supplements above except HEPES and with final concentrations of 3 mM calcium and 3 mM phosphate), and the treatment with test items started by adding the desired final concentration of each compound to the culture medium. See Table 16.

[0469] For each compound, a total of seven concentrations was tested in four replicates, in addition to the negative (DMEM standard medium) and positive (DMEM osteogenic medium without inhibitors) controls. See Table 16. Table 16 Group Medium [Compound] (µM) (N) Negative control Standard 0 4 Positive control Osteogenic 0 4 Compound 47 0.1 Osteogenic 0.1 4 Compound 47 0.3 Osteogenic 0.3 4 Compound 47 1 Osteogenic 1 4 Compound 47 3 Osteogenic 3 4 Compound 47 10 Osteogenic 10 4 Compound 47 30 Osteogenic 30 4 Compound 47 100 Osteogenic 100 4 Compound 480.1 Osteogenic 0.1 4 Compound 480.3 Osteogenic 0.3 4 Compound 481 Osteogenic 1 4 Compound 483 Osteogenic 3 4 Compound 4810 Osteogenic 10 4 Compound 4830 Osteogenic 30 4 Compound 48100 Osteogenic 100 4 Compound 530.1 Osteogenic 0.1 4 Compound 530.3 Osteogenic 0.3 4 Compound 531 Osteogenic 1 4 Compound 533 Osteogenic 3 4 Compound 5310 Osteogenic 10 4 Compound 5330 Osteogenic 30 4 Compound 53100 Osteogenic 100 4

[0470] Media (including the corresponding concentration of treatments) was changed three days per week (every 2-3 days). The culture was stopped after 14 days. 2. Culture calcification determination

[0471] Total calcium content deposited per wells was collected at the end of the experiment by incubating the cells overnight (37 ºC, 5% CO2) with 500 µL of 0.6 N hydrochloric acid (HCl). The HCl supernatant was collected to determine calcium concentration.

[0472] Total protein content per well was obtained by lysing the cells with the addition of 500 µL 0.1 N NaOH – 0.1% SDS to the well right after collecting the HCl sample.

[0473] Calcium content in the HCl samples was measured by Inductively Coupled Plasma - Optical Emission Spectrometer (ICP-OES). Calcium samples were diluted 1 / 20 with Milli-Q® water to a final volume of 4 mL. For calcium content quantification, a 12- point standard curve with calcium concentrations ranging between 0.025 to 50 mg / L was prepared using CaCO3 as a calcium source. Both standards and samples were analyzed by ICP-OES using HNO31% as carrier and the radial plasma view at 315.887 nm.

[0474] Protein content of the cell culture was quantified by the Bradford method. An 8- point standard curve with bovine serum albumin concentrations ranging between 0.1 and 1.5 mg / dL was prepared. Bradford reagent was added to all samples or standards in duplicate and the mixture was incubated for 10 minutes with constant agitation. The absorbance at 595 nm was read in a microplate spectrophotometer.

[0475] The calcification of each sample was expressed as µg Ca / mg protein. The percentage of inhibition was calculated per each sample using the positive control as reference of maximum calcification.

[0476] For calcium concentration, a one-way ANOVA with Tukey’s multiple comparison test as post-hoc was performed for each compound independently. For inhibition of calcification, a two-way ANOVA with two-stage linear step-up procedure of Benjamini, Krieger and Yekutieli as post-hoc was performed. The two factors included in this two-way ANOVA were the inhibitor and the concentration. A concentration- response curve was generated using a nonlinear regression model (variable slope, four parameters) and the IC30, IC50, IC80 and IC95 were calculated. See Table 17. All the statistics were performed using GraphPad Prism version 9 (GraphPad Software, La Jolla, CA, USA, www.graphpad.com). Table 17 Compound 47 Compound 48 Compound 53 IC50 µM (CI 95%) 8.7 (NC) 8.2 (NC) 14 (NC-19) IC30 µM (CI 95%) 8.1 (7.3-8.4) 7.5 (6.0-8.1) 11 (9.1-15) IC80 µM (CI 95%) 9.7 (8.8-10) 9.5 (7.6-10) 19 (16-26) IC95 µM (CI 95%) 11 (10-12) 11 (9.0-12) 27 (23-37) Emax % (CI 95%) 96 (89-103) 97 (89-105) 96 (85-111)

[0477] The results showed that the IP5 substituted compounds tested were effective in inhibiting the calcification of hVSMC in vitro in a concentration-response manner. The tested compounds inhibited calcification in hVSMC showing slightly different profiles in terms of potency and maximum efficacy. See Fig.10.

[0478] This data demonstrates that the IP5 substituted compounds of the invention could be used for treating a wide range of conditions related to ectopic calcification. Exemplary instances of such conditions include, but are not limited to, aortic calcification, aortic valve calcification, aortic stenosis, calcific aortic valve stenosis, atherosclerosis, arteriosclerosis, aneurysm or coral reef aorta.

[0479] Arterial calcification leads to stiffening of the vessels, indicating the potential use of these compounds in arterial stiffness. Stiffening of the aorta leads to decreased filling of the coronary vessels during diastole and reduced perfusion of the myocardium, indicating that these compounds could be used in coronary disease or coronary artery disease. Decreased coronary filling can lead to the inability of the myocardium to adequately respond to increased oxygen demand resulting in ischemia, even in the absence of coronary artery obstruction. Inadequate response to increased myocardial oxygen demand can lead to symptoms of myocardial ischemia and angina. Hence, these compounds could be used in myocardial ischemia and angina pectoris (including chronic stable angina) due to its impact on aortic calcification and consequently, all the downstream effects towards ischemia and chest pain. Arterial stiffening also forces the heart to pump harder and hypertrophy, indicating that the compounds of the invention could be used in left ventricular hypertrophy. Ultimately, arterial stiffening and heart hypertrophy may lead to arrhythmias, heart failure, congestive heart failure, cardiac disease, cardiovascular mortality or cardiac death, indicating that the compounds of the invention could be used in these situations or conditions.

[0480] Similarly, these results would support the use of the compounds of the invention for inhibiting ectopic calcification in the kidneys (e.g., nephrocalcinosis, renal lithiasis), the femoral arteries (e.g., PAD, CLI) or other soft tissue (e.g., PXE). Example 3 Treatment of Calcific Aortic Valve Stenosis

[0481] The dose-response efficacy of IP5 substituted compounds in the treatment of calcified aortic human valves was analyzed using an in vitro model (Zabirnyk A, et al., Vasc Pharmacol 2019; 122-123, 106583, doi:10.1016 / j.vph.2019.106583).

[0482] The model evaluated the effects of Compound 6 (SNF532) on the calcification of interstitial cells from aortic human valves (VIC). Human calcified aortic valve leaflets were obtained during aortic valve replacement and were harvested. After the removal of the valve endothelial cells, VIC were isolated. The leaflets were placed in 30 mL of basic growth medium (DMEM), supplemented with 10% fetal bovine serum (FBS) and 50 μg / mL gentamycin with the addition of 1 mg / mL collagenase II. The cells were incubated overnight at 37 °C with 5% CO2. Next day, the digested tissue was homogenized by pipetting with a serological pipet and centrifuged at 300 g for 5 min and the supernatant carefully removed by aspiration.

[0483] The pellet was washed in 10 mL of fresh DMEM and centrifuged as described previously. The supernatant was removed by aspiration, the cell pellet was resuspended in basic growth media and seeded in 75 cm3flasks. VIC were cultured at 37 °C and 5% CO2 with growth media changed twice a week until they reached ~90% confluency. Cells were passaged at ratio of 1:2, propagated and frozen. 1. VIC osteogenic differentiation and inhibition

[0484] For osteogenic differentiation, VIC from calcified human aortic valves were seeded in 24-well tissue culture plates at 30 x 104cells / well in basic growth medium and cultured overnight at 37 °C, 5% CO₂. The following day, osteogenic differentiation was induced by supplementing the medium with 50 μM ascorbic acid, 0.1 μM dexamethasone and 10 mM β-glycerophosphate. Osteogenic medium was changed twice a week for three weeks. The negative control group (no induction of calcification) was cultivated in basic growth media for the same period of time and media was changed following the same protocol.

[0485] The concentration-response study was performed with the same VIC donors in all groups. Increasing concentrations (1, 3, 10, 30, and 100 µM) of Compound 6 (SNF532) were incubated starting at week 1 when the osteogenic differentiation was induced and compared with the activity of IP6. A positive control group (osteogenic medium with no inhibitors added) was performed using VIC from the same donors. 2. Calcium staining and quantification

[0486] Alizarin Red staining was performed to assess calcification. The cell medium was removed, the cells were washed with PBS and fixed with 70% ethanol for 1 h at room temperature. Then, cells were washed with Milli-Q water and stained with Alizarin Red according to the manufacturer's instructions. To quantify calcium accumulation, Alizarin Red staining was extracted and measured spectrophotometrically. Briefly: for 24-well plate, 200 μL10% acetic acid was added to each well and incubated for 30 min at room temperature with gentle agitation. After that, cells were detached using a cell scraper and the resulting suspension was transferred to a 1.5 mL microcentrifuge tube and vortexed vigorously for 30 s. The cells were then heated to 85 °C for 10 min before the tubes were transferred to ice for 5 min and chilled. Then, the cells were centrifuged at 15000 g for 15 min. The supernatant was transferred to a new 1.5 mL microcentrifuge tube, 75 μL of 1M NaOH were added to each tube to achieve a pH between 4.1 and 4.5. Finally, 50 μL from the tube were transferred to a clear bottom 96-well plate and the absorbance at 405 nm was measured on a plate reader.

[0487] Statistics were analyzed by GraphPad Prism (version 9, Dotmatics, Boston, MA, US). The VIC cultures which failed to differentiate and calcify under osteodifferentiation media were excluded. Normality of the data was assessed using a Shapiro-Wilk test. For results that were normally distributed, a one-way ANOVA for normal distribution with DMS post-test was applied. For the results that were not normally distributed, a non- parametric one-way ANOVA (Kruskal–Wallis test) with Dunn's post-test was applied. Relative calcification results are shown as dot plots and mean. A value of p < 0.05 was considered statistically significant.

[0488] The results showed that IP5 substituted Compound 6 (SNF532) was effective in inhibiting the calcification of VIC in vitro in a dose-response manner. See Fig. 11. The results indicate that these compounds could be used in situations or conditions like valvular calcification, valve stenosis or calcific aortic valve stenosis. Calcified valves can lead to heart hypertrophy, indicating that these compounds could be used to treat or prevent left ventricular hypertrophy. Ultimately, heart hypertrophy may lead to arrhythmias, heart failure, congestive heart failure, cardiac disease, cardiovascular mortality or cardiac death, indicating that these compounds could be used in these situations or conditions. Example 4 Treatment of Calcinosis Cutis and Calciphylaxis

[0489] The dose-response efficacy of IP5 substituted compounds in the prevention and treatment of calcinosis cutis and calciphylaxis (CUA) induced by vitamin D3 and FeCl3 in a rat model was used. The model evaluated the effects of two IP5 substituted compounds on the formation of calcified skin plaques in rats for a duration of 8 days. Animals were sensitized at a concentration of 50,000 IU / kg vitamin D3. A FeCl3 solution (0.5 mg / kg) was used as challenger to induce the formation of skin plaques. All animals were weighed every day before treatment.

[0490] Thirty-four male Sprague Dawley (SD) rats (Inotiv, Indianapolis, IN, USA) weighing approximately 250 g were used. The animals were fed with a standard LASQCdiet® Rod14-H diet (LASvendi, Soest, DE). The animals were divided in 4 groups, as follows:

[0491] Group 1 – Control (sham), 4 animals. Animals in group 1 were administered subcutaneously physiological saline (0.9% (w / v) NaCl solution daily from D1 to D3 in the interscapular space, and with one saline 0.9% injection at each of the two ventral sites in the thorax on D4. Animals in group 1 were not administered Vit D or FeCl3 solutions.

[0492] Group 2 – Physiological saline solution (Vehicle): Vit D 50,000 IU / kg, 0.5 mg / kg FeCl3 solution, 10 animals. Vit D at dose 50,000 IU / kg was administered subcutaneously x 3 consecutive days (D1, D2, D3), and one 0.5 mg / kg FeCl3 injection at each of the two ventral sites in the thorax on D4.

[0493] Group 3 – Compound X: Vit D 50,000 IU / kg, 0.5 mg / kg FeCl3, 10 animals. Vit D at dose 50,000 IU / kg was administered subcutaneously x 3 consecutive days (D1, D2, D3), and one 0.5 mg / kg FeCl3 injection at each of the two ventral sites in the thorax on D4. This group received a daily Compound X sc treatment at the selected dose (D1 to D8).

[0494] Group 4 – Compound Y: Vit D 50,000 IU / kg, 0.5 mg / kg FeCl3, 10 animals. Vit D at dose 50,000 IU / kg was administered subcutaneously x 3 consecutive days (D1, D2, D3), and one 0.5 mg / kg FeCl3 injection at each of the two ventral sites in the thorax on D4. This group received a daily Compound Y sc treatment at the selected dose (D1 to D8).

[0495] On D8, all animals were exsanguinated and sacrificed. Their necropsies were performed and samples (i.e., aorta, carotids, femorals, heart, right kidney, skin tissue plaque at the FeCl3 injection sites, blood) were collected for calcium content measurement. The tissues were cleaned with 0.15 M saline solution and lyophilized for 48-72 h and weighed. The lyophilized tissues were then digested using a 1:1 HNO3:HClO4 mixture in a dry bath incubator for 2-4 h at 180°C. The digested tissues were subsequently diluted using Milli-Q water (MilliporeSigma, Merck KGaA, Burlington, MA, US) to a final volume of 5 mL (for femoral and carotid) or 10 mL (for heart, kidney, aorta and skin plaque). Calcium content was quantified via inductively coupled plasma optical emission spectrometry (ICP-OES) using an Optima 7300 DV ICP-OES System spectrometer (PerkinElmer, Inc., Waltham, MA, US) according to the manufacturer’s instructions. Total magnesium, calcium, phosphorus, potassium, sodium, and zinc levels were analyzed in serum samples via ICP-OES. Example 5 Treatment of Pseudoxanthoma elasticum

[0496] A stable CRISPR / Cas9 abcc6a- / -zebrafish model characterized for spinal column hypermineralization was used for assaying the efficacy of Compound X in the treatment of Pseudoxanthoma elasticum (PXE; Van Gils M, et al., J Invest Dermatol 2022; 138:2333-2342).

[0497] Abcc6a- / -larvae were treated with Compound X at different concentrations (i.e., 100 µM to 1000 µM) for 7 days, starting at 3 days post fertilization (dpf), with daily refreshment of the medium containing the solved compounds. On 10 dpf, the larvae were euthanized and stained with Alizarin Red to visualize the spinal column hypermineralization, using a Leica M165 FC microscope (Leica Microsystems GmbH, Wetzlar, DE). Semi-quantification of calcification was done through image processing with ImageJ image processing with ImageJ (Rasband W, Research Services Branch, NIH, Bethesda, MD, US). ***

[0498] It is to be appreciated that the Detailed Description section, and not the Summary and Abstract sections, is intended to be used to interpret the claims. The Summary and Abstract sections may set forth one or more but not all exemplary embodiments of the present invention as contemplated by the inventor(s), and thus, are not intended to limit the present invention and the appended claims in any way.

[0499] The present invention has been described above with the aid of functional building blocks illustrating the implementation of specified functions and relationships thereof. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternate boundaries can be defined so long as the specified functions and relationships thereof are appropriately performed.

[0500] The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying knowledge within the skill of the art, readily modify and / or adapt for various applications such specific embodiments, without undue experimentation, without departing from the general concept of the present invention. Therefore, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments, based on the teaching and guidance presented herein. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, such that the terminology or phraseology of the present specification is to be interpreted by the skilled artisan considering the teachings and guidance.

[0501] The breadth and scope of the present invention should not be limited by any of the above-described examples but should be defined only in accordance with the following claims and their equivalents.

Claims

CLAIMS 1. A compound of general formula I:a pharmaceutically acceptable salt thereof, or a combination thereof, wherein (i) R1, R2, R3, R5, and R6 independently represent -OPO3H2 and R4 is a substituent group of formula II or formula III, or R1, R2, R3, R4, and R5 independently represent -OPO3H2 and R6 is a substituent group of formula II or formula III,(ii) R1, R3, R4, R5, and R6 independently represent -OPO3H2 and R2 is a substituent group of formula II or formula III, (iii) R1, R2, R3, R4, and R6 independently represent -OPO3H2 and R5 is a substituent group of formula II or formula III, (iv) R2, R3, R4, R5, and R6 independently represent -OPO3H2 and R1 is a substituent group of formula II; or R1, R2, R4, R5, and R6 independently represent - OPO3H2 and R3 is a substituent group of formula II or formula III, wherein, for formula II, n is an integer between 1 and 30, wherein the terminal group X is selected from the group consisting of -H, -OR, -NRR', -COOR, - CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO2R, -NHCONRR', halogen, - CF3, alkyl, alkenyl, alkynyl, carbocycle, and heterocycle, and wherein R and R' are H or an alkyl group, and wherein, for formula III, y and y’ are an integer between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selectedfrom the group consisting of alkyl, -COR, -OR, -NRR', -COOR, -CONRR', - NHCOR, -NHCOOR, -OCONR -NHSO2R, -NHCONRR', halogen, and -CF3, and wherein R and R' are H or an alkyl group, for use in the treatment, inhibition of progression, and prevention of ectopic calcification or the consequences thereof in a subject in need thereof.

2. Compound for use according to claim 1, wherein the compound is a compound of general formula IV, V, VI, VII, VIII, IX, X or XI, and any combination thereof.

3. Compound for use according to any one of claims 1 to 2, wherein the compound is selected from the group consisting of Compound 1 to Compound 53, and any combination thereof.

4. Compound for use according to claim 3, wherein the compound is a Compound 1 (SNF524) of chemical structure:.

5. Compound for use according to claim 3, wherein the compound is a Compound 6 (SNF532) of chemical structure:.

6. Compound for use according to claim 3, wherein the compound is a Compound 47 (SNF733) of chemical structure:.

7. Compound for use according to claim 3, wherein the compound is a Compound 48 (SNF734) of chemical structure:.

8. Pharmaceutical composition for use in the treatment, inhibition of progression, or prevention of ectopic calcification or the consequences thereof in a subject in need thereof comprising a compound for use according to any one of claims 1 to 7 and any combination thereof, and at least one pharmaceutically acceptable excipient or carrier.

9. Compound or pharmaceutical composition for use according to any of the preceding claims, wherein a therapeutically effective amount of the compound or pharmaceutical composition is administered to the subject in need thereof.

10. Compound or pharmaceutical composition for use according to any of the preceding claims, comprising the treatment, inhibition of progression, and prevention of a disease and / or condition related to ectopic calcification or the consequences thereof in a subject in need thereof.

11. Compound or pharmaceutical composition for use according to claim 10, wherein the ectopic calcification or the consequences thereof comprise adrenal and intracranial calcification in familial cerebral cavernous malformations, adynamic bone, age-related macular degeneration (AMD) related to calcium deposits, bone cancer, bone mineral disease, breast calcification, calcific band keratopathy, calcific tendinitis, calcification in osteoarthritis, calcification of articular cartilage in osteoarthritis, calcification of joints and arteries (CALJA), calcification of the seminal vesicles, calcinosis cutis, calciphylaxis (CUA), calcium pyrophosphate deposition disease (CPPD), cardiovascular diseases or associated conditions, chondrocalcinosis, colon cancer, diabetic kidney disease, dystrophic calcification, failure of renal transplant grafts, familial cerebral cavernous malformations (FCCM), fibrodysplasia ossificans progressiva (FOP), hyperostosis- hyperphosphatemia syndrome (HHS), hyperphosphatemic familial tumoral calcinosis (HFTC), idiopathic brain calcification (Fahr's disease), idiopathic mesenteric phlebosclerosis (IMP), kidney stones (renal lithiasis), metastatic calcification, nephrocalcinosis, neurocysticercosis-related calcification, osteomalacia, osteoporosis, pineal calcification, phlebosclerotic colitis, podagra, primary familial brain calcification (PFBC), primary hyperoxaluria (PH), pseudoxantoma elasticum (PXE), rheumatoid arthritis, sialolithiasis, Sjorgen's syndrone parotid glands calcification, seminal vesicle calculi, skin cancer, soft tissue calcification owing to sarcoidosis, Wolman's disease adrenal calcification, and wound healing related to diabetic ulcers.

12. Compound or pharmaceutical composition for use according to claim 11, wherein the cardiovascular diseases or associated conditions comprise acute ischemic stroke (ACS), aneurysm, angina pectoris (chronic stable angina), aortic artery calcification, aortic calcification, aortic stenosis, aortic valve calcification, arrhythmia, arteriosclerosis, arterial stiffness, arteriovenous fistula (AVF) failure, atherosclerosis, calcific aortic valve stenosis (CAVS or AVS), cardiac death, cardiac disease, cardiovascular calcification, cardiovascular disease in chronic kidney disease (CKD) patients, cardiovascular disease linked to aging, cardiovascular mortality, cerebrovascular disease, congestive heart failure, coral reef aorta (CRA), coronary artery calcification, coronary artery disease, coronary disease, critical limb ischemia, electrocardiographic abnormalities, general arterial calcification of infancy (GACI), heart failure, hypertension, ischaemia, left ventricular hypertrophy, major adverse cardiovascular events (MACE) in hemodialysis (HD) patients, Mönckeberg's medial sclerosis (MMS), myocardial calcification, myocardial infarction, myocardial ischemia, pericardial calcification, peripheral arterial disease (PAD), peripheral vascular disease (PVD), porcelain aorta and calcification of anastomosis site after coronary artery bypass grafting (CABG), portal vein calcification, stroke, thrombosis, valvular calcification, and vascular calcification.

13. Compound or pharmaceutical composition for use according to any of the preceding claims, wherein the subject is with kidney failure.

14. Compound or pharmaceutical composition for use according to any of the preceding claims, wherein the subject is on dialysis.

15. Compound or pharmaceutical composition for use according to any of the preceding claims, wherein the administration is topical, enteral or parenteral.

16. Compound or pharmaceutical composition for use according to claim 15, wherein the parenteral administration is intravenous, subcutaneous, intramuscular or by intravenous infusion.

17. Compound or pharmaceutical composition for use according to claim 16, wherein the intravenous infusion is administered using a dialysis apparatus.

18. Compound or pharmaceutical composition for use according to any of the preceding claims, wherein the subject is human.

19. A kit or article of manufacture comprising at least one compound or pharmaceutical composition for use according to any one of the preceding claims, and any combination thereof.

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