IP5-substituted compounds

Abstract

The invention provides an IP5-substituted compound as shown in a general formula I, and a synthesis method and application thereof. The IP5-substituted compounds of the present invention are characterized by having-O (alkyl) nX and-O (alkyl) yCy (alkyl) y '-Z chains in positions R1, R2, R4 and R5. Also provided are methods, pharmaceutical compositions and formulations, methods of use, articles of manufacture, and kits for treating diseases and conditions, such as pathological crystallization-related diseases and conditions.

Description

Technical Field

[0001] The present invention relates to IP5-substituted compounds, synthesis methods and uses thereof. Background Art

[0002] Crystallization and deposition of calcium salts are common phenomena. Usually, these processes are physiologically necessary for individual health. However, sometimes, it may become abnormal and / or pathological, leading to various diseases and conditions affecting the vascular and renal systems, which usually have devastating consequences (Khan S et al., "Pathological crystallization of calcium oxalate and calcium phosphate" in "Hydroxyapatite and Related Materials", 1st edition, Brown P et al. (CRC Press, Boca Raton, FL, US, 1994, Chapter 5). Hydroxyapatite (HAP) (formula Ca 10 (PO 4 ) 6 (OH) 2 Calcium phosphate) was identified as the agent involved in pathological crystallization (Grases F et al., Cir J 2007; 71: 1152-1156).

[0003] Several crystallization inhibitors that can affect the formation and growth of HAP have been described in the prior art, such as pyrophosphates, bisphosphonates (e.g., etidronate, alendronate, ibandronate) and phytates (Lomashvili K et al., J Am Soc Nephrol 2004; 15: 1392-1401, Bevilacqua M et al., Lupus 2005; 14: 773-779, Price P et al., Arterioscler Thromb Vase Biol 2001; 21: 817-824, Price P et al., J Nutr 2001; 131: 2910-2915, Grases F et al., Front Biosci 2006; 11: 136-142). Recently, many phytate-related compounds (e.g., myo-inositol pentaphosphate (IP5) substituted derivatives) have been suggested for various applications, including inhibition of HAP and / or prevention and treatment of pathological crystallization. For example, WO2011064559 and Wang H et al., Chem Biol 2014; 21: 689-699 disclose the use of IP5 derivatives for treating cancer. WO2009061393 and Huang X et al., ACS Appl Mater Interfaces 2017; 9: 10435-10445 describe the use of IP5 derivatives as biological tools and calcium chelators, respectively. In addition, WO2021219135, W02017098047 and W02020058321 describe the use of these compounds for treating calcium-related pathologies. However, there is still a need in the art for new IP5 substituted derivatives that can effectively inhibit HAP formation and growth and / or pathological crystallization. Summary of the invention

[0004] The present invention discloses a compound of general formula I:

[0005]

[0006] A pharmaceutically acceptable salt thereof, or a combination thereof, wherein

[0007] (i)R 1 , R 2 , R 3 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 4 is a substituent of formula II or III, or R 1 , R 2 , R 3 , R 4 and R 5Independently represent OPO 3 H 2 , and R 6 is a substituent of formula II or formula III,

[0008]

[0009] (ii) R 1 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 2 is a substituent of formula II or formula III,

[0010] (iii) R 1 , R 2 , R 3 , R 4 and R 6 Independently expressed -OPO 3 H 2 , and R 5 is a substituent of formula II or formula III,

[0011] (iv) R 2 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 1 is a substituent of formula II; or R 1 , R 2 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 3 is a substituent of formula II or formula III,

[0012] 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, -NHSO 2 R, -NHCONRR', halogen, -CF 3, alkyl, alkenyl, alkynyl, carbocyclic (saturated or unsaturated) and heterocyclic (saturated or unsaturated), and wherein R and R' are H or alkyl groups, and wherein, for Formula III, y and y' are integers between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the following: alkyl, -COR, -OR, -NRR', -COOR, -CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', halogen and -CF 3 , and wherein R and R' are H or alkyl groups.

[0013] In some aspects, the compound of Formula I is selected from Compound 1 to Compound 53.

[0014] In some aspects, the pharmaceutically acceptable salt is a sodium salt or a magnesium salt. In some aspects, the sodium salt is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, a decasodium salt or an undecasodium salt.

[0015] The present invention also provides a pharmaceutical composition comprising the compound of formula I disclosed above and at least one pharmaceutically acceptable excipient.

[0016] Also provided is a method of inhibiting the formation or growth of calcium salts / crystals (e.g., calcium phosphate, hydroxyapatite (HAP)) in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a pharmaceutical composition disclosed herein.

[0017] In addition, the present invention provides a method for treating or preventing a disease or condition associated with pathological crystallization in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a pharmaceutical composition disclosed herein.

[0018] Also provided is a method of inhibiting the progress of the crystallization process in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a pharmaceutical composition disclosed herein.

[0019] The present invention also provides a method for restoring or increasing blood perfusion in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula I, or a pharmaceutical composition disclosed herein.

[0020] In some aspects, the subject is a human. In some aspects, administration is topical, enteral, or parenteral administration. In some aspects, parenteral administration is intravenous administration. In some aspects, intravenous administration is administration by bolus or by infusion.

[0021] 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 use according to any method disclosed herein. In some aspects, the kit or article of manufacture may further comprise at least one compound selected from the group consisting of the compounds listed in Table 1.

[0022] In some aspects, the present invention further provides a method for preparing a compound of Formula I (eg, Compound 1 to Compound 53), comprising using at least one compound selected from the group consisting of the compounds listed in Table 1. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1A and Figure 1B Representative structures of compounds I_A:IP5-4 substituted compounds are shown.

[0024] Figure 2A and Figure 2B Representative structures of compounds I_B:IP5-2 substituted compounds are shown.

[0025] Figure 3 Representative structures of compounds substituted with Compound I_C:IP5-5 are shown.

[0026] Figure 4 Compound I_D: Representative structures of compounds substituted with IP5-1.

[0027] Figure 5 is a schematic diagram of synthetic scheme 1.

[0028] Figure 6 is a schematic diagram of synthetic scheme 2.

[0029] Fig. 7A and Figure 7B Schematic diagrams of synthetic schemes 3 and 6, respectively.

[0030] Fig. 8A and Figure 8B Schematic diagrams of synthetic schemes 4 and 7, respectively.

[0031] Fig.9A and Fig. 9B Schematic diagrams of synthetic schemes 5 and 8, respectively. DETAILED DESCRIPTION

[0032] The present invention provides IP5 substituted compounds, their synthesis methods and uses. In some aspects, the IP5 substituted compound is a compound of formula I:

[0033]

[0034] Its pharmaceutically acceptable salt, or a combination thereof, wherein

[0035] (i)R 1 , R 2 , R 3 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 4 is a substituent of formula II or III, or R 1 , R 2 , R 3 , R 4 and R 5 Independently expressed -OPO 3 H 2 , and R 6 is a substituent of formula II or III, (see Figure 1A , 1B )

[0036]

[0037] (ii) R 1 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 2 is a substituent of formula II or III, (see Figure 2A , 2B )

[0038] (iii) R 1 , R 2 , R 3 , R 4 and R 6 Independently expressed -OPO 3 H 2 , and R 5 is a substituent of formula II or III, (see Figure 3 )

[0039] (iv) R 2 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 1 is a substituent of formula II; or R 1 , R 2 , R 4 , R5 and R 6 Independently expressed -OPO 3 H 2 , and R 3 is a substituent of formula II or formula III (see Figure 4 ),

[0040] 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, -NHSO 2 R, -NHCONRR', halogen, -CF 3 , alkyl, alkenyl, alkynyl, carbocyclic (saturated or unsaturated) and heterocyclic (saturated or unsaturated), and wherein R and R' are H or alkyl groups, and wherein, for Formula III, y and y' are integers between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the following: alkyl, -COR, -OR, -NRR', -COOR, -CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', halogen and -CF 3 , and wherein R and R' are H or alkyl groups. In some aspects, the IP5 substituted compound is a compound of Formula IV, V, VI, VII, VII, VIII, IX, X or XI.

[0041] In some aspects, the IP5 substituted compound is a sodium salt or a magnesium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, a decasodium salt or an undecasodium salt.

[0042] Also provided are methods, pharmaceutical compositions and formulations, methods of use, articles of manufacture, and kits for treating diseases and conditions, such as diseases and conditions associated with pathological crystals.

[0043] In order to make it easier to understand the present invention, specific terms are first defined below. As used in this application, unless otherwise expressly stated herein, the following terms should have the meanings set forth below. Other definitions are set forth throughout the application.

[0044] I. Definitions

[0045] The invention includes aspects in which exactly one member of the group is present in, utilized in, or relevant to a given product or method. The invention includes aspects in which more than one or all members of the group are present in, utilized in, or relevant to a given product or method.

[0046] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those of ordinary skill in the art to which the present invention relates. For example, A Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd edition, 2002, CRC Press; A Dictionary of Cellular and Molecular Biology, 3rd edition, 1999, Academic Press; and The Oxford Dictionary of Biochemistry and Molecular Biology, revised in 2000, Oxford University Press, provide a general dictionary of many of the terms used in the present invention for those skilled in the art.

[0047] Units, prefixes and symbols are expressed in the form accepted by the International System of Units (SI). Numerical ranges include the numbers defining the range. In the case of a range of recorded values, it is understood that each intermediate integer value and each fraction thereof between the recorded upper and lower limits of the range and each subrange between these values ​​are also specifically disclosed. The upper and lower limits of any range may be independently included in the range or excluded from the range, and each range including one endpoint value, both endpoint values ​​do not include, or both endpoint values ​​include is also encompassed within the present invention.

[0048] Where values ​​are explicitly stated, it is understood that values ​​of approximately the same quantity or amount as the stated values ​​are also within the scope of the invention. Where combinations are disclosed, each subcombination of the elements of the combination is also specifically disclosed and is within the scope of the invention. Conversely, where different elements or groups of elements are disclosed individually, combinations thereof are also disclosed. Where any element of the invention is disclosed as having multiple alternatives, examples of the invention in which each alternative is excluded individually or in any combination with other alternatives are also disclosed; more than one inventive element may have such exclusions, and all combinations of elements having such exclusions are also disclosed.

[0049] About: As used herein, the term "about" refers to a value or composition that is within an acceptable error range for a 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, according to the practice in the art, "about" can mean within 1 or more than 1 standard deviation. Alternatively, "about" can mean a range of up to 20%. In addition, particularly with respect to biological systems or methods, the term can mean up to an order of magnitude or up to 5 times a value.

[0050] When a specific value or composition is provided in the present application and claims, unless otherwise stated, the meaning of "about" should be assumed to be within the acceptable error range of the specific value or composition. When the term "about" is used in conjunction with a numerical range, it modifies the range by extending the boundaries above and below the listed numerical values. Thus, "about 10-20" means "about 10 to about 20". In general, the term "about" can modify numerical values ​​above and below the stated value with a variance of, for example, 10% above or below (higher or lower).

[0051] And / or: As used herein, "and / or" is taken as a specific invention of each of the two specified features or components with or without the other. Thus, the term "and / or" as used herein in phrases such as "A and / or B" is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Similarly, the term "and / or" as used in phrases such as "A, B and / or C" is intended to cover each of the following: 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).

[0052] 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 claimed 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 of a value in either direction (greater or less than) of a claimed reference value, unless otherwise stated or apparent from the context (except where the number would exceed 100% of the possible value).

[0053] Bolus administration: As used herein, the terms "bolus administration" and "bolus injection" refer to a rapid intravenous injection lasting less than 10 seconds, or an intravenous infusion lasting less than 3 minutes.

[0054] Comprising: It is to be understood that in any aspects described herein with the language "comprising," similar aspects described with "consisting of" and / or "consisting essentially of" are also provided.

[0055] Compound: As used herein, the term "compound" is intended to include any and all free bases, isomers, and isotopes of the depicted structure. As used herein, the term "isomer" refers to any geometric isomer, tautomer, zwitterion, stereoisomer, enantiomer, or diastereomer of a compound. A compound may include one or more chiral centers and / or double bonds, and may therefore 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 stereoisomerically pure forms (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure), as well as enantiomeric and stereoisomeric mixtures (e.g., racemates). Enantiomers and stereoisomeric mixtures of compounds and methods of resolving them into their component enantiomers or stereoisomers are well known. The compounds, salts or complexes of the invention can be prepared by combining with solvents or water molecules to form solvates and hydrates by conventional methods. In some aspects, the term compound is used to refer to IP5 substituted compounds of the invention.

[0056] Effective amount: As used herein, the term "effective amount" of a therapeutic agent, with respect 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 and one or more additional therapeutic agents, is an amount sufficient to produce a beneficial or desired result. In some aspects, a beneficial or desired result is, for example, a clinical result, and thus an "effective amount" depends on the context in which it is applied. The term "effective amount" can be used interchangeably with "effective dose", "therapeutically effective dose" or "therapeutically effective dose".

[0057] The term effective amount relates to the specific use of the IP5 substituted compound. For example, when the IP5 substituted compound is used to inhibit the formation or growth of calcium salts / crystals (e.g., calcium phosphate, HAP), the effective amount will be the amount of the IP5 substituted compound that can achieve the desired effect (e.g., reducing HAP crystallization / formation in serum or plasma).

[0058] Enteral administration: As used herein, the term "enteral administration" and the related term "enteral" refer to any administration of the IP5-substituted compounds of the present invention or pharmaceutical compositions comprising the compounds via the gastrointestinal tract. Enteral administration includes, but is not limited to, oral, sublingual, and rectal administration routes.

[0059] Prevention: As used herein, the term "prevention" refers to measures taken to maintain health and prevent or delay the onset of a disease or condition, or to alleviate its extent and / or the severity of symptoms. Therefore, the preventive use of the therapeutic agents disclosed herein (e.g., (i) IP5 substituted compounds of the present invention, or (ii) combinations 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 (v) IP5 substituted compounds of the present invention and one or more additional therapeutic agents) corresponds to an amount sufficient to produce a beneficial or desired result.

[0060] Ranges: As described herein, any concentration range, percentage range, ratio range, or integer range is to be understood to include any integer value within the recited range, and fractions thereof (such as tenths and hundredths of integers) where appropriate, unless otherwise indicated.

[0061] IP5 of the present invention replaces compound: As used herein, the term "IP5 of the present invention replaces compound" and its grammatical variants refer to the compound of formula I, wherein its substituent is disclosed in the compound family I_A, I_B, I_C and I_D and its salt (for example, its pharmaceutically acceptable salt) described in detail below. In some aspects, the term IP5 of the present invention replaces compound covers compound 1 to 53, any salt thereof (for example, sodium salt), and any combination thereof. In some aspects, the term IP5 of the present invention replaces compound covers compound of formula I, which is an intermediate in the synthesis of compound 1 to 53, for example, a compound selected from the group consisting of the compounds listed in Table 1, any salt thereof (for example, sodium salt), and any combination thereof. In some aspects, the term IP5 of the present invention replaces compound covers 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 (for example, sodium salt), and any combination thereof.

[0062] The group consisting of Compound 1 to Compound 53: In the context of the present invention, reference to the "group consisting of Compound 1 to Compound 53" refers to a group of compounds comprising Compound 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 includes combinations thereof. In some aspects, the combination of compounds from the group consisting of Compound 1 to Compound 53 can include 2, 3, 4, 5, 6, 7, 8, 9, 10 or more compounds from the group consisting of Compound 1 to Compound 53.

[0063] The group consisting of the compounds listed in Table 1: In the context of the present invention, the reference to "the group consisting of the compounds listed in Table 1" refers to the group of intermediate compounds used for, for example, synthesizing the IP5-substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 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 includes combinations thereof. In some aspects, the combination of compounds from the group consisting of the compounds listed in Table 1 can include 2, 3, 4, 5, 6, 7, 8, 9, 10 or more compounds from the group consisting of the compounds listed in Table 1.

[0064] Non-bolus administration: As used herein, the terms "non-bolus" and "non-bolus administration" refer to an intravenous injection lasting 10 seconds or more, or an intravenous infusion lasting 3 minutes or more.

[0065] Parenteral administration: As used herein, the term "parenteral administration" and the related term "parenteral" refer to the administration of the IP5-substituted compound of the present invention characterized by the physical destruction of the subject's tissue, and the administration of the compound by the destruction in the tissue. Parenteral administration includes, but is not limited to, administering the 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, for example, surgical incision or by applying a compound or composition via a non-surgical wound that penetrates the tissue. In particular, parenteral administration includes, but is not limited to, epidural, intraarterial, intradermal, intrathecal, intramuscular, intraperitoneal, intrasternal injection, intravascular, intravenous, intravenous infusion, intraspinal, subcutaneous, and subcutaneous reservoir administration routes.

[0066] Subject: "Subject" or "individual" or "animal" or "patient" or "mammal" refers to any subject, particularly a mammalian subject, for whom diagnosis, prognosis or treatment is desired. Mammalian subjects include, but are not limited to, humans, livestock, farm animals, zoo animals, sports animals, pet animals, such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates, such as apes, monkeys, gorillas and chimpanzees; canines, such as dogs and wolves; felines, such as cats, lions and tigers; equines, such as horses, donkeys and zebras; bears; edible animals, such as cows, pigs and sheep; ungulates, such as deer and giraffes; rodents, such as mice, rats, hamsters and guinea pigs, etc. In certain aspects, the mammal is a human subject. In other aspects, the subject is a human patient. In a specific aspect, the subject is a human patient who has or is at risk of having pathological crystals.

[0067] Substantially: As used herein, the term "substantially" refers to the qualitative condition of exhibiting a full or nearly full degree or measure of a characteristic or property of interest. One of ordinary skill in the biological arts will appreciate that biological and chemical phenomena rarely, if ever, reach completion and / or proceed to completeness, or achieve or avoid an absolute result. Thus, the term "substantially" is 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 compositions comprising IP5-substituted compounds of the present invention, which can provide significant therapeutic benefits to subjects in need thereof. In some aspects, subjects in need thereof are subjects suffering from or at risk of developing a disease or condition associated with pathological crystals (e.g., calcium phosphate or HAP crystals). Therefore, in general, the 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, which is administered in an amount sufficient to produce a beneficial or desired result.

[0069] The term therapeutic agent also encompasses preventive, diagnostic or imaging agents comprising IP5-substituted compounds 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 inhibit calcium salts / crystallization (e.g., calcium phosphate, HAP) formation or growth and / or that can improve and / or prevent any symptoms associated with pathological crystallization.

[0070] Topical administration: As used herein, the term "topical administration" and the related term "topical" refer to any administration of the IP5-substituted compound of the present invention or a pharmaceutical composition comprising the compound to a specific location (such as skin or mucous membrane) on or in the body. Topical administration includes, but is not limited to, ear, skin, nasal, transdermal, urethral, ​​vaginal and urethral administration routes.

[0071] Treating, treatment, therapy: As used herein, the term "treating" or "treatment" or "therapy" refers to partially or completely alleviating, ameliorating, improving, alleviating, delaying the onset of one or more symptoms or characteristics of a disease, inhibiting its progression, reducing its severity, reducing its incidence; or any combination thereof.

[0072] Treatments comprising IP5-substituted compounds of the present invention may be administered to subjects who do not show signs of a disease, disorder, and / or condition, and / or who show only early signs of a disease, disorder, and / or condition, for purposes such as (i) reducing the risk of developing pathology associated with the disease, disorder, and / or condition, (ii) delaying the onset of the disease, disorder, and / or condition, or pathology associated with the disease, disorder, and / or condition, or (iii) alleviating the symptoms and / or sequelae of the disease, disorder, and / or condition, or pathology associated with the disease, disorder, and / or condition.

[0073] Thus, in general, the term "treat" refers to counteracting the effects caused by a disease or pathological condition of interest in a subject, including (i) inhibiting the disease or pathological condition, in other words, slowing or halting its development or progression; (ii) relieving the disease or pathological condition, in other words, causing regression of the disease or pathological condition or its symptoms; (iii) stabilizing the disease or pathological condition; and (iv) any combination thereof.

[0074] ug, uM, uL: As used herein, the terms "ug," "uM," and "uL" are used interchangeably with "μg," "μM," and "μL," respectively.

[0075] II. IP5-substituted compounds

[0076] The present invention provides IP5 substituted compounds, their synthesis methods and uses. In some aspects, the IP5 substituted compound is a compound of formula I:

[0077]

[0078] Its pharmaceutically acceptable salt, or a combination thereof, wherein

[0079] R 1 , R 2 , R 3 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 4 is a substituent of formula II or III, or R 1 , R 2 , R 3 , R 4 and R 5 Independently expressed -OPO 3 H 2 , and R 6 is a substituent of formula II or formula III,

[0080]

[0081] R 1 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 2 is a substituent of formula II or formula III,

[0082] R 1 , R 2 , R 3 , R 4 and R 6 Independently expressed -OPO 3 H 2 , and R 5 is a substituent of formula II or formula III,

[0083] R 2 , R 3 , R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 1 is a substituent of formula II; or R 1 , R 2, R 4 , R 5 and R 6 Independently expressed -OPO 3 H 2 , and R 3 is a substituent of formula II or formula III,

[0084] 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, -NHSO 2 R, -NHCONRR', halogen, -CF 3 , alkyl, alkenyl, alkynyl, carbocyclic (saturated or unsaturated) and heterocyclic (saturated or unsaturated), and wherein R and R' are H or alkyl groups, and wherein, for Formula III, y and y' are integers between 0 and 10, wherein Cy is a cyclic linker, wherein the terminal group Z is selected from the following: alkyl, -COR, -OR, -NRR', -COOR, -CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', halogen and -CF 3 , and wherein R and R' are H or alkyl groups. In some aspects, the IP5 substituted compound is a compound of Formula IV, V, VI, VII, VII, VIII, IX, X or XI.

[0085] In some aspects, not all of the negative charges in the IP5-substituted compounds of the invention can be removed by positively charged ions (e.g., Na + , Ca ++ Mg ++) charge compensation. Therefore, the compound substituted by IP5 of the present invention can be, for example, tetraionic salt (for example, tetrasodium salt), pentaionic salt (for example, pentasodium salt), hexaionic salt (for example, hexasodium salt), heptaionic salt (for example, heptasodium salt), octaionic salt (for example, octasodium salt), nonaionic salt (for example, nonaionic salt), decaionic salt (for example, decaionic salt) or elevenionic salt (for example, eleven sodium salt). In some aspects, the presence of additional negatively charged groups in the compound substituted by IP5 can lead to complex formation with additional ions. In some aspects, the compound substituted by IP5 of the present invention is a sodium salt. In some aspects, the compound substituted by IP5 is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a hexasodium salt, a heptasodium salt, a nonacid salt, a decasodium salt or an eleven sodium salt. In some aspects, the compound substituted by IP5 is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the compound substituted by IP5 is a hexasodium salt, an octasodium salt, a nonacid salt or a decasodium salt. Formula I and other formulae presented in this invention are intended to encompass any isomers of the compounds covered thereby.

[0086] In the context of the present invention, the term "alkenyl" or "alkenyl chain" refers to a substituted or unsubstituted straight or branched alkyl chain (e.g., containing between 2 and 10 carbon atoms) containing one or more double bonds. Examples include ethenyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl and 1,3-butadienyl.

[0087] In the context of the present invention, the term "alkyl" or "alkyl chain" refers to a saturated hydrocarbon moiety, which may 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 to, C 1 -C 4 Alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl or isobutyl, and cycloalkyl, such as cyclohexyl. The term alkyl can be extended to alkyl groups connected or bridged by heteroatoms. In the context of the present invention, heteroatoms are nitrogen (N), sulfur (S), oxygen (O) and halogen.

[0088] In the context of the present invention, the term "alkynyl" or "alkynyl chain" refers to a substituted or unsubstituted straight or branched alkyl chain (e.g., containing between 2 and 10 carbon atoms) containing one or more triple bonds. Examples include ethynyl, propynyl, 1-butynyl and 3-butynyl.

[0089] An "amine functional group" or "amine group" is a functional group NRR', wherein R and R' are independently selected from, for example, hydrogen (-H) and alkyl, such as C 1 -C n Alkyl, wherein n is an integer between 0 and 30.

[0090] A "hydroxyl functional group" or "hydroxyl group" is OH.

[0091] A "carboxylic acid functional group" or "carboxylic acid group" is COOH or its anion COO - .

[0092] "Carboxamide" is CONRR' or NCOR, wherein R and R' are independently selected from, for example, hydrogen (-H) and alkyl, such as C 1 -C n Alkyl, wherein n is an integer between 0 and 20.

[0093] "Carbocycle" refers to a three- to ten-membered carbon ring which may be saturated, partially unsaturated or aromatic (eg, phenyl, cyclopentyl, cyclopropyl) and is bonded to the rest of the molecule through any available C atom.

[0094] "Heterocycle" refers to a 3- to 10-membered ring containing at least one heteroatom selected from N, O and S, which may be saturated, partially unsaturated or aromatic (e.g., triazole, piperazine, pyrazole), and is bonded to the rest of the molecule through any available C or N atom. The term includes heterocycles substituted with one or more halogen atoms.

[0095] "Cy" refers to a cyclic linker including a carbocyclic ring or a heterocyclic ring. Examples of carbocyclic and heterocyclic rings include 1,3-phenyl, 1,4-phenyl, naphthyl, thienyl, furanyl, pyrrolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl, pyridinyl, piperazinyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzimidazolyl, benzofuranyl, isobenzofuranyl, indolyl, isoindolyl, benzothienyl, benzothiazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, azetidinyl, and aziridine.

[0096] A "halogen" group refers to fluorine, chlorine, bromine or iodine.

[0097] In the context of the present invention, the term "-OPO 3 2- "It does not explicitly refer to -OPO 3 H - and-OPO 3 H 2 .

[0098] In some aspects, the IP5 substituted compounds of the present invention or the intermediate compounds disclosed herein can be detected and / or quantified using the methods disclosed in US9612250. See also, US8377909, US8778912 and US20070066574.

[0099] The IP5-substituted compounds of the present invention can exist in any form commonly used in pharmaceutical technology. Specific aspects include, but are not limited to, sodium salts, magnesium salts, potassium salts, ammonium salts, free acids or mixtures of the aforementioned forms. Other pharmaceutically acceptable salts are known to those skilled in the art and can be obtained by methods previously described (Haynes M et al., J. Pharmaceutical Sci. 2005; 94: 2111-2120).

[0100] In some aspects, IP5 substituted compounds of the present invention include or consist of IP5 substituted compounds selected from compounds 1 to 53 and combinations thereof. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 1. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 2. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 3. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 4. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 5. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 6. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 7. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 8. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 9. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 10. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 11. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 12. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 13. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 14. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 15. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 16. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 17. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 18. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 19. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 20. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 21. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 22. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 23. In some aspects, the IP5 substituted compounds of the present invention include compound 24 or consist of it. In some aspects, the IP5 substituted compounds of the present invention include compound 25 or consist of it. In some aspects, the IP5 substituted compounds of the present invention include compound 26 or consist of it. In some aspects, the IP5 substituted compounds of the present invention include compound 27 or consist of it. In some aspects, the IP5 substituted compounds of the present invention include compound 28 or consist of it. In some aspects, the IP5 substituted compounds of the present invention include compound 29 or consist of it.In some aspects, IP5 substituted compounds of the present invention include or consist of compound 30. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 31. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 32. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 33. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 34. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 35. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 36. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 37. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 38. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 39. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 40. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 41. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 42. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 43. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 44. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 45. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 46. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 47. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 48. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 49. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 50. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 51. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 52. In some aspects, IP5 substituted compounds of the present invention include or consist of compound 53.

[0101] The IP5 substituted compounds of the present invention are disclosed in myo form.

[0102] The present invention also provides chemical intermediate compounds that can be used to prepare IP5 substituted compounds of the present invention (e.g., compounds 1 to compounds 53). In some aspects, such intermediates are compounds listed in Table 1. Intermediate compounds disclosed herein can be converted into IP5 substituted compounds of the present invention by utilizing the procedures described herein. Therefore, the present invention provides methods for producing IP5 substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 53), comprising utilizing intermediate compounds of the group consisting of compounds listed in Table 1. The present invention also provides methods for producing intermediate compounds disclosed herein. Therefore, the present invention provides methods for producing intermediate compounds of the group consisting of compounds listed in Table 1, for producing IP5 substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 53).

[0103] In some aspects, the IP5-substituted compounds of the present invention include or consist of compounds of the formula:

[0104]

[0105] Where n is an integer between 1 and 30, and alkyl is CH 2 and X is -H, -OH, -OMe, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', -CF 3 , alkyl, cyclopropane, cyclopentane or pyrazole. Figure 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, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 5, and the alkyl group is CH 2 and X is -H (Compound 1). In some aspects, n is 3, alkyl is CH 2 and X is -H (Compound 24). In some aspects, n is 1, alkyl is CH 2 and X is -H (Compound 22). In some aspects, n is 5, alkyl is CH 2and X is -OH (Compound 2). In some aspects, n is 10, alkyl is CH 2 and X is -OH (Compound 21). In some aspects, n is 5, alkyl is CH 2 and X is -OMe (Compound 3). In some aspects, n is 7, alkyl is CH 2 and X is -OMe (Compound 23). In some aspects, n is 5, alkyl is CH 2 and X is -COOH (Compound 4). In some aspects, n is 10, alkyl is CH 2 and X is -COOH (Compound 20). In some aspects, n is 3, alkyl is CH 2 and X is -CH(CH 3 ) 2 (Compound 12). In some aspects, n is 5, alkyl is CH 2 and X is -CF 3 (Compound 13). In some aspects, n is 5, alkyl is CH 2 and X is -NHCOMe (Compound 19). In some aspects, n is 2, alkyl is CH 2 and X is cyclopentane (Compound 16). In some aspects, n is 2, alkyl is CH 2 and X is cyclopropane (Compound 17). In some aspects, n is 5, alkyl is CH 2 and X is pyrazole (Compound 18). In some aspects, n is 5, alkyl is CH 2 and X is -CONH 2 (Compound 33).

[0106] In some aspects, n is an integer between 3 and 30, and alkyl is CH 2 and X is an amine group. Figure 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, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, and the alkyl group is CH 2 and X is -NH 2(Compound 27). In some aspects, n is 6, alkyl is CH 2 and X is -NH 2 (Compound 28).

[0107] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0108]

[0109] Where n is an integer between 1 and 30, and alkyl is CH 2 and X is -H, -OH, -OMe, amine, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', -CF 3 , cyclopropane, cyclopentane, pyrazole or alkynyl groups. Figure 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 compound substituted by IP5 is a sodium salt. In some aspects, the compound substituted by IP5 is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the compound substituted by IP5 is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the compound substituted by IP5 is a hexasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the compound substituted by IP5 is an octasodium salt. In some aspects, n is 5 and alkyl is CH 2 and X is -H (Compound 6). In some aspects, n is 3, alkyl is CH 2 and X is -H (Compound 34). In some aspects, n is 5, alkyl is CH 2 and X is -OH (Compound 40). In some aspects, n is 5, alkyl is CH 2 and X is -OMe (Compound 7). In some aspects, n is 9, alkyl is CH 2 and X is -OMe (Compound 8). In some aspects, n is 19, alkyl is CH 2 and X is -OMe (Compound 9). In some aspects, n is 29, alkyl is CH 2 and X is -OMe (Compound 10). In some aspects, n is 5, alkyl is CH 2and X is -NHCOMe (Compound 35). In some aspects, n is 5, alkyl is CH 2 and X is -CF 3 (Compound 36). In some aspects, n is 5, alkyl is CH 2 and X is -CONH 2 (Compound 37). In some aspects, n is 2, alkyl is CH 2 and X is cyclopentane (Compound 38). In some aspects, n is 2, alkyl is CH 2 and X is cyclopropane (Compound 39). In some aspects, n is 1, alkyl is CH 2 and X is C≡CH (Compound 43).

[0110] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0111]

[0112] Where n is an integer between 1 and 30, and alkyl is CH 2 and X is -H, -OH, -OMe, amine, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', -CF 3 , cyclopropane, cyclopentane or pyrazole. Figure 3 A. 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, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, and the alkyl group is CH 2 and X is -H (Compound 29). In some aspects, n is 9, alkyl is CH 2 and X is -OMe (Compound 31). In some aspects, n is 5, alkyl is CH 2 and X is -OMe (Compound 44). In some aspects, n is 5, alkyl is CH 2 and X is -CF 3(Compound 45). In some aspects, n is 2, alkyl is CH 2 and X is cyclopropane (Compound 30).

[0113] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0114]

[0115] Where n is an integer between 1 and 30, and alkyl is CH 2 and X is -H, -OH, -OMe, amine, pyrazole, triazole, -COOH, CONRR', -NHCOR, -NHCOOR, -OCONR, -NHSO 2 R, -NHCONRR', -CF 3 , cyclopropane, cyclopentane or pyrazole. Figure 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, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt. In some aspects, n is 3, and the alkyl group is CH 2 and X is -H (Compound 32). In some aspects, n is 9, alkyl is CH 2 and X is -OMe (Compound 47). In some aspects, n is 5, alkyl is CH 2 and X is -NHCOMe (Compound 49). In some aspects, n is 5, alkyl is CH 2 and X is -CF 3 (Compound 50). In some aspects, n is 2, alkyl is CH 2 and X is cyclopropane (Compound 48). In some aspects, n is 2, alkyl is CH 2 and X is cyclopentane (Compound 51).

[0116] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0117]

[0118] Where y and y' are integers between 0 and 10, and alkyl is CH 2 , 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 -CH 3 , -OMe, -CF 3 、COCH 3 and -COOH 3 See also Figure 1B . In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt or a 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, and alkyl is CH 2 , Cy is 1,4-substituted phenyl, and Z is -CH 3 (Compound 11). In some aspects, y is 3, y' is 0, and alkyl is CH 2 , Cy is 1,4-substituted phenyl and Z is -OMe (Compound 14). In some aspects, y is 3, y' is 0, alkyl is CH 2 , Cy is 1,3-substituted phenyl and Z is -CF 3 (Compound 15). In some aspects, y is 2, y' is 0, and alkyl is CH 2 , Cy is piperazine and Z is -COCH 3 (Compound 5). In some aspects, y is 3, y' is 2, and alkyl is CH 2 , Cy is triazole-1 and Z is -COOH (Compound 25). In some aspects, y is 6, y' is 0, alkyl is CH 2 , Cy is triazole-1 and Z is -COOH (Compound 26).

[0119] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0120]

[0121] Wherein y and y' are integers between 0 and 10, and alkyl is CH 2 , 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 -CH 3 , -OMe, -CF3 、COCH 3 and -COOH 3 See also Figure 2B . In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt or a 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, and alkyl is CH 2 , Cy is triazole-1, and Z is -OMe (Compound 41). In some aspects, y is 1, y' is 2, alkyl is CH 2 , Cy is triazole-2, and Z is -COOH (Compound 46).

[0122] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0123]

[0124] Wherein y and y' are integers between 0 and 10, and alkyl is CH 2 , 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 -CH 3 , -OMe, -CF 3 、COCH 3 and -COOH 3 See also Figure 3 . In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt or a 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, and alkyl is CH 2 , Cy is triazole-1, and Z is -OMe (Compound 42).

[0125] In some aspects, the IP5-substituted compounds of the present invention include or consist of the following compounds:

[0126]

[0127] Wherein y and y' are integers between 0 and 10, and alkyl is CH 2 , 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 -CH 3 , -OMe, -CF 3 、COCH 3 and -COOH 3 See also Figure 4 . In some aspects, the IP5 substituted compound is a sodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, or an octasodium salt. In some aspects, the IP5 substituted compound is a hexasodium salt, an octasodium salt, a nonasodium salt, or a decasodium salt. In some aspects, the IP5 substituted compound is an octasodium salt or a 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, and alkyl is CH 2 , Cy is triazole-1, and Z is -OMe (Compound 52). In some aspects, y is 1, y' is 2, alkyl is CH 2 , Cy is triazole-2, and Z is -COOH (Compound 53).

[0128] Table 1

[0129] Intermediates

[0130]

[0131]

[0132]

[0133]

[0134]

[0135]

[0136]

[0137]

[0138]

[0139]

[0140] The IP5 substituted compounds of the present invention and the intermediates for their synthesis can be synthesized by using the methods described herein and other methods known in the field of organic chemistry. In some aspects, the methods include, but are not limited to, the general procedures shown in Synthetic Schemes 1, 2, 3, 4, 5, 6, 7 and 8 described herein. Therefore, in some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 1 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 2 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 3 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 4 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 5 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 6 disclosed below. In some aspects, the present invention provides a method for preparing an IP5 substituted compound of the present invention, which includes applying Synthetic Scheme 7 disclosed below. In some aspects, the present invention provides a method of preparing an IP5 substituted compound of the present invention comprising applying Synthetic Scheme 8 disclosed below.

[0141] In some aspects, the present invention provides a method for preparing an intermediate for synthesizing an IP5-substituted compound of the present invention (e.g., a compound selected from the group consisting of compound 1 to compound 53), which comprises applying any one of synthetic schemes 1, 2, 3, 4, 5, 6, 7 or 8 disclosed below (as applicable).

[0142] Scheme 1: In general, the IP5-substituted compound of the present invention (i.e., compound I_A) can be obtained by deprotecting the intermediate of formula IV_A (Scheme 1). The "protecting group" or GP can be (not limited to) benzyl, levulinyl benzyl, tert-butyl, o,o'-xylyl (by combining 2 PGs in the same phosphate), 9-fluorenylmethyl, cyanoethyl, and other suitable protecting groups in each case. The intermediate of formula IV_A can be achieved by phosphorylation of the intermediate of formula III_A according to the procedures described in the literature (such as reaction with phosphine amidine derivatives and subsequent oxidation). At the same time, the intermediate of formula III_A can be obtained by hydrolysis of the intermediate of formula II_A in an acidic medium. Finally, the intermediate of formula II_A can be obtained by alkylating the intermediate (2) using an alkylating agent. The preparation of (2) has been described previously 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 can be (without limitation) chloride, bromide, iodide, tosyl (Ts) or mesyl (Ms). See Figure 5 .

[0143] Option 2: As an alternative to Option 1, when R 4 or R 6 When containing substituted 1,2,3-triazoles, 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 by using intermediates of formula VI_A as starting materials and alkynyl "click agents" via click reactions. Intermediate VI_A can be obtained by alkylation and hydrolysis of intermediate 2 with appropriate reagents. As another alternative, when R 4 or R 6 When containing a terminal amine group, compounds of formula I_A can be obtained by phosphorylation of compound VI_A to obtain compound VII-A, and by subsequent deprotection / reduction of such compounds. Figure 6 .

[0144] Scheme 3: Compound I_B can be obtained using a similar synthetic route used for compound I_A. Therefore, compound I_B can be obtained by deprotecting an intermediate of formula IV_B (Scheme 3). The intermediate of formula IV_B can be obtained by phosphorylating an intermediate of formula III_B. At the same time, the intermediate of formula III_B can be obtained by hydrolysis of an intermediate of formula II_B or VIII_B in an acidic medium. The intermediate of formula VIII_B can be obtained by debenzylation of intermediate II_B'. Finally, the intermediate of formula II_B or B' can be obtained by alkylation of intermediate (3) or (4) using an alkylating agent, respectively. The preparation of (3) and (4) has been previously described in the prior 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 R 2 When containing substituted 1,2,3-triazoles, compounds of formula I_B can be obtained by following an alternative route. In this way, intermediates of formula III_B can also be obtained by using alkynyl intermediates of formula III_B as starting materials and azide "click agents" via click reactions. See Fig. 7A .

[0145] Scheme 4: Compound I_C can be obtained by deprotecting the intermediate of formula IV_C (Scheme 4). The intermediate of formula IV_C can be obtained by phosphorylating the intermediate of formula IV_C. The intermediate of formula III_C can be obtained by debenzylation of intermediate II_C. Finally, the intermediate of formula II_C can be obtained by alkylation of intermediate (33) using a suitable alkylating agent. The preparation of (33) has been previously described in the prior art (Phenix C. et al., ChemBioChem 2008; 9(10): 1591-1602). See Fig. 8A .

[0146] Scheme 5: Compound I_D can be obtained by deprotecting an intermediate of formula IV_D (Scheme 5). The intermediate of formula IV_D can be obtained by phosphorylating an intermediate of formula III_D. The intermediate of formula III_D can be obtained by debenzylation of intermediate IX_D. Intermediate IX-D can be obtained by hydrolysis of intermediate II_D. Finally, the intermediate of formula II_D can be obtained by alkylation of intermediate (34) using a suitable alkylating agent. The preparation of racemate (34) is already in the prior art (Chen, 2015, supra). As an alternative, when R 2When containing substituted 1,2,3-triazoles, compounds of formula I_D can be obtained by following an alternative route. In this way, intermediates of formula IX_D can also be obtained by using alkynyl intermediates of formula IX_D as starting materials and azide "click agents" via click reactions. See Fig.9A .

[0147] Option 6: As an alternative to Option 3, when R 2 When containing substituted 1,2,3-triazole or acrylamide, the compound of formula I_B can be obtained by following the alternative route described in Scheme 6. In this way, the intermediate of formula III_B can also be obtained by using the azide intermediate of formula V_B as the starting material and the alkynyl "click agent" through a click reaction. Intermediate V_B can be achieved by alkylation of intermediate 3 using a suitable reagent. As another alternative, when R 2 When containing a terminal acrylamide group, the compound of formula III_B can be obtained by amidation of the corresponding amino compound III_B. Figure 7B .

[0148] Scheme 7: As an alternative to Scheme 4, when R 5 When containing substituted 1,2,3-triazole, the compound of formula I_C can be obtained by following the alternative route described in Scheme 7. In this way, the intermediate of formula II_C can also be obtained by using the azide intermediate of formula V_C as the starting material and the alkynyl "click agent" through the click reaction. Intermediate V_C can be achieved by alkylation of intermediate 33 using a suitable reagent. See Figure 8B .

[0149] Scheme 8: As an alternative to Scheme 5, when R 1 or R 3 When containing substituted 1,2,3-triazoles, 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 also be obtained by using alkynyl intermediates of formula V_C (wherein X is a triple bond) as starting materials and azide "click agents" via click reactions. Intermediate V_C (wherein X is a triple bond) can be achieved by alkylation of intermediate 34 and subsequent hydrolysis of the alkene-protected compound II_D. As another alternative, when R 1 or R 3 When containing an alkyl group, the intermediate of formula III_D (wherein the alkyl group is R 1 ) can be obtained via debenzylation of intermediate IX_D, where X corresponds to a triple bond. Fig.9A .

[0150] Provided herein are representative IP5 substituted compounds of the present invention (e.g., compounds selected from compound 1 to compound 53) and all of them in myo configuration. However, it should be understood that any exemplary IP5 substituted compound of the present invention in myo configuration is not limited to the representative configuration shown. Therefore, for example, compounds 1 to 53 and intermediates provided herein are in myo configuration. With this configuration, natural myo isomers have a structure in which five of the six hydroxyls (the first, third, fourth, fifth, and sixth) are in equatorial positions and the second hydroxyl is axial.

[0151] The present invention also provides a method for preparing a drug for treating pathological crystallization, which comprises 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 compound 1 to compound 53) for use as a drug. Also provided is the use of a compound of formula I (e.g., selected from compound 1 to compound 53) for preparing a drug for preventing or treating a disease associated with pathological crystallization.

[0152] III. Pharmaceutical Compositions

[0153] The present invention also provides pharmaceutical compositions for use in the methods of preventing and / or treating the diseases and conditions disclosed herein (e.g., pathological crystallization), wherein the pharmaceutical composition comprises at least one IP5 substituted compound of the present invention (e.g., a compound selected from 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 Compound 1 to Compound 53) alone or together with one or more pharmaceutically acceptable excipients or carriers.

[0154] The term "excipient" as used herein refers to a substance that aids in the absorption of an element in a pharmaceutical composition, stabilizes the element, activates, or aids in the 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), cosolvents (e.g., ethanol), buffers, tonicity agents (e.g., NaCl), and pH adjusting factors (e.g., carbonate, citrate, phosphate solutions).

[0155] As in the case of excipients, a "pharmaceutically acceptable carrier" is a substance used in a composition to dilute any component contained therein to a defined volume or weight (e.g., 0.9% (w / v) NaCl aqueous solution). A pharmaceutically acceptable carrier is an inert substance, or a substance having a similar effect to any element comprising the pharmaceutical composition of the present invention. The function of the carrier is to allow the incorporation of other elements, to allow for better dosing and administration, or to provide consistency and shape to the composition.

[0156] The pharmaceutical composition may comprise from approximately 1% to approximately 95% active ingredient. In some aspects, for example, the pharmaceutical composition of the present invention may comprise from approximately 20% to approximately 90% active ingredient (i.e., IP5 substituted compounds of the present invention or combinations thereof, alone or, for example, in combination with one or more additional therapeutic agents).

[0157] The preparation of the pharmaceutical composition suitable for parenteral administration comprises an active ingredient, for example, a compound substituted by IP5 of the present invention (for example, a compound selected from the group consisting of compound 1 to compound 53), which is combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline (for example, 0.9% (w / v) NaCl aqueous solution). Such a preparation can be prepared, packaged or sold in a form suitable for push injection or non-pull injection. Injectable preparations can be prepared, packaged or sold in unit dosage form, for example in ampoules or in multi-dose containers containing preservatives. Preparations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions, pastes and implantable sustained-release or biodegradable preparations in oily or aqueous carriers. Such a preparation may further include one or more additional ingredients, including but not limited to suspensions, stabilizing or dispersing agents.

[0158] In some aspects, in formulations for parenteral administration, the active ingredient, e.g., an IP5-substituted compound of the invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53) is provided in a dry form (i.e., powder or granules) for reconstitution with a suitable carrier (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition.

[0159] Pharmaceutical compositions can be prepared, packaged or sold in the form of sterile injectable aqueous or oily suspensions or solutions. The suspensions or solutions can be prepared according to known techniques and, in addition to active ingredients (e.g., inositol phosphates of the present invention), may also include additional ingredients such as dispersants, wetting agents or suspending agents as described herein. Such sterile injectable preparations can be prepared using nontoxic parenteral acceptable diluents or solvents, such as water or 1,3-butanediol. Other acceptable diluents and solvents include, but are not limited to, Ringer's solution, isotonic sodium chloride solution and fixed oils, such as synthetic monoglycerides or diglycerides.

[0160] Other useful administrable formulations include those containing active ingredients in microcrystalline form, liposome formulations, or as components of biodegradable polymer systems. Compositions for sustained release or implantation may include pharmaceutically acceptable polymers or hydrophobic materials, such as emulsions, ion exchange resins, slightly soluble polymers, or slightly soluble salts. Compositions and methods for preparing preparations for administering IP5-substituted compounds of the present invention (including controlled release or sustained release preparations containing the active agent) are described in the art. See, for example, Remington: The Science and Practice of Pharmacy, 23rd edition, 2021, Academic Press. Press); US6340475, US6488962, US6451808, US5972389, US5582837 and US5007790; US20030147952, US20030104062, US20030104053, US20030044466, US20030039688 and US20020051820; WO2003035041, WO2003035 040, WO2003035029, WO2003035177, WO2003035039, WO2002096404, WO2002032416, WO2001097783, WO2001056544, WO2001032217, WO1998055107, WO1998011879, WO1997047285, WO1993018755 and WO1990011757.

[0161] The medicaments according to the invention are prepared by methods known in the art, in particular by conventional mixing, coating, granulating, dissolving or lyophilizing.

[0162] The invention also provides a compound or combination of compounds or pharmaceutical preparation 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.

[0163] The invention also provides a compound or combination of compounds or a pharmaceutical preparation according to any of the above aspects of the invention, in the broadest definition given, or as specified in any aspect presented above, for use in the treatment and / or prevention of a disease or condition disclosed herein.

[0164] The present invention also provides a compound or combination of compounds or pharmaceutical preparation according to any of the above aspects of the invention, in the broadest definition given, or as specified in any aspect presented above, for use in the preparation of a medicament for the prevention and / or treatment of a disease or condition disclosed herein.

[0165] IV. Products and Kits

[0166] The present invention also provides products and kits. Such products and kits may include a container (e.g., a box) comprising one or more vials containing a preparation comprising one or more IP5-substituted compounds of the present invention (e.g., a compound selected from the group consisting of compound 1 to compound 53) and / or a solvent for its medical administration or other uses according to the methods disclosed herein.

[0167] The kit or article provided according to the present invention may also include a manual or instructions, which describes the method and dosage of medical administration disclosed herein, or uses the compound substituted by IP5 of the present invention according to the methods disclosed herein (e.g., a compound selected from the group consisting of compound 1 to compound 53). In some aspects, the kit or article may include multiple vials, each of which contains a single dose. In other aspects, the kit or article may include one or more vials, each of which contains more than one dose.

[0168] In some aspects, the article 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 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 is a bag containing a powdered form of an IP5-substituted compound of the present invention (e.g., a compound selected from the group consisting of compound 1 to compound 53), which is used to be reconstituted in a suitable solvent. In other aspects, the article is a bottle (e.g., a glass bottle or a plastic bottle) containing a powdered form of an IP5-substituted compound of the present invention (e.g., a compound selected from the group consisting of compound 1 to compound 53), which is used to be reconstituted in a suitable solvent.

[0169] Kits and articles of manufacture can include instructions for one or more administrations of an IP5-substituted compound of the invention (eg, a compound selected from the group consisting of Compound 1 to Compound 53) according to the methods and dosages disclosed herein.

[0170] The instructions included in the kits and articles of manufacture may be attached to the packaging material or may be included as a package insert. Although the instructions are typically written or printed materials, they are not limited thereto. 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., disks, tapes, cassettes, chips), optical media (e.g., CD ROMs), etc. As used herein, the term "instructions" may include the address of an Internet website that provides the instructions. V. Uses of IP5-substituted compounds of Formula I

[0171] The present invention provides methods for treating diseases and conditions using IP5 substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 53). In some aspects, the medical uses disclosed herein relate to the ability of IP5 substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 53) to inhibit the formation or growth of calcium salts / crystals (e.g., calcium phosphate, HAP) in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula I or a pharmaceutical composition disclosed herein. Therefore, IP5 substituted compounds of the present invention (e.g., compounds selected from the group consisting of compounds 1 to 53) can be used to treat and prevent diseases and conditions associated with pathological crystallization.

[0172] The present invention provides a method for treating and / or preventing pathological crystallization and / or its consequences in a subject in need thereof, comprising administering an IP5-substituted compound of the present invention (e.g., a compound selected from the group consisting of Compound 1 to Compound 53), wherein administration of the IP5-substituted compound is effective in treating and / or preventing pathological crystallization and / or its consequences in the subject.

[0173] The present invention also provides a method for preparing a medicament for treating pathological crystallization, comprising using an intermediate compound selected from the group consisting of the compounds listed in Table 1. Also provided is a compound selected from the group consisting of Compound 1 to Compound 53 for use in treating pathological crystallization and / or its consequences in a subject in need thereof.

[0174] In some aspects, the IP5-substituted compounds of the present invention (eg, compounds selected from the group consisting of Compound 1 to Compound 53) can be administered topically, enterally, or parenterally.

[0175] A. Synthesis of protected myo-inositol agents, alkylating agents or click agents and activated acids A.1. Synthesis of protected myo-inositol agents (1), (2), (3), (4), (31), (32), (33) and (34)

[0176] 1,3,5-O-Methyl-myo-inositol (1): The synthesis of (1) has been described previously in the literature (Martin S et al., J. Org. Chem. 1994; 59(17): 4805-4820).

[0177] 2-O-tert-Butyldimethylsilyl-1,3,5-O-methy1-myo-inositol (2): The synthesis of (2) has been previously described in the literature (Kadirvel, 2008, supra).

[0178] 4,6-Bis-O-(4-methoxybenzyl)-1,3,5-O-methy1-myo-inositol (3): The synthesis of (3) was previously described in the literature (Aiba, 2016, supra).

[0179] 4,6-Di-O-benzyl-1,3,5-O-methy1-myo-inositol (4): The synthesis of (4) was previously described in the literature (Chen, 2015, supra).

[0180] 2,4,6-Tri-O-benzyl-1,3,5-O-methy1-myo-inositol (31): The synthesis of (31) was previously described in the literature (Song F et al., Org Biomol Chem 2012; 10:3642-3654).

[0181] 2,4,6-Tri-O-benzyl-myo-inositol (32): The synthesis of (32) was previously described in the literature (Chen, 2015, supra).

[0182] 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).

[0183] 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).

[0184] A.2. Synthesis of alkylating agents or click agents

[0185] l-(4-(2-Chloroethyl)piperazin-l-yl)ethanone (5): To a solution of l-(4-(2-hydroxyethyl)piperazin-l-yl)ethanone (1.74 g, 10.10 mmol) in dichloromethane (DCM, 0.2 M) at 0°C, triethylamine (TEA, 2.1 mL, 15.15 mmol) and Ts-Cl (2.31 g, 12.12 mmol) were added. The reaction mixture was stirred at room temperature for 72 h and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, DCM:MeOH (MeOH) (95:5)) to give 1.28 g (5) (yield 66%). HPLC-MS (Condition A): rt = 0.24 min; m / z: 191, 193 [M, M+2] + .

[0186] 9-Methoxynonyl 4-methylbenzenesulfonate (7):

[0187]

[0188] Step 1: 9-methoxynonan-1-ol (6): A mixture of 9-bromononan-l-ol (0.5 g, 2.24 mmol) and sodium methoxide 4N (25 mL, 100 mmol) was stirred at 40°C for 18 h. The mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, hexane (Hex): ethyl acetate (EtOAc) 4:1) to give 324 mg (6) (yield 83%). 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).

[0189] Step 2: 9-Methoxynonyl-4-methylbenzenesulfonate (7): To a solution of (6) (1.5 g, 8.61 mmol) in DCM (28.7 mL) was added TEA (1.80 mL, 12.91 mmol) and Ts-Cl (2.13 g, 11.19 mmol). The reaction mixture was stirred at room temperature for 24 h, then quenched with water and washed with brine. The organic layer was washed with Na 2 SO 4Dry, filter and concentrate in vacuo. The residue was purified by flash chromatography (silica gel, Hex: EtOAc 4: 1) to give 2.15 g (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).

[0190] 4-Methylbenzenesulfonic acid 19-methoxy 19-10-yn-1-ester (13):

[0191]

[0192] Step 1: 2-((9-Bromononyl)oxy)dihydro-2H-pyran (8): To a mixture of 9-bromononan-l-ol (2.18 g, 9.77 mmol) and p-TsOH (37 mg, 0.19 mmol) was added 3,4-dihydro-2H-pyran (1.3 mL, 14.65 mmol). The reaction mixture was stirred at 60 °C for 3.5 days. The mixture was diluted with water, extracted with ether (2x), and washed with Na 2 SO 4 Dry, filter and remove the solvent in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 9:1) to afford 2.4 g (8) (yield 80%). 1 H-NMR was the same as described previously (Grube A et al., Eur J Org Chem 2006; 1285-1295).

[0193] Step 2: Dec-9-yn-1-methanesulfonate (9): To a solution of dec-9-yn-1-ol (5.22 g, 33.8 mmol) in THF (0.35 M) was added TEA (6.3 mL, 44 mmol) and Ms-Cl (3.5 mL, 44 mmol) at 0°C. The reaction mixture was stirred at room temperature for 16 h and diluted with water, extracted with DCM (x2), and washed with Na 2 SO 4 Dry, filter and remove the solvent in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc (20:1)) to afford 8.1 g of (9) (yield >99%). 1H-NMR is the same as described in the previous literature (Langmuir: the ACS journal of surfaces and colloids., 2013, Vol. 29(2), p. 570-580).

[0194] Step 3: 10-Methoxydec-1-yne (10): To (9) (8.17 g, 35.2 mmol) was added a 5 M solution of sodium methoxide in MeOH (35.2 mL, 176 mmol). The reaction mixture was stirred at 45 °C for 18 h. The mixture was diluted with water, extracted with ether (2x), and washed with Na 2 SO 4 Dry, filter and remove the solvent in vacuo. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 20:1) to afford 4 g (10) (yield 67%). 1 H NMR (400 MHz, CHLOROFORM-d) δ 3.34 (td, J = 6.6, 1.0 Hz, 2H), 3.31 (s, 3H), 2.15 (tdd, 7 = 7.1, 2.7, 1.0 Hz, 2H), 1.91 (td, 7 = 2.7, 1 Hz, 1H), 1.62-1.45 (m, 4H), 1.41-1.23 (m, 8H).

[0195] Step 4: 2-((19-methoxynonadeca-10-yn-1-yl)oxy)dihydro-2H-pyran (11): A 1.6M hexane solution of n-BuLi (7.45 mL, 11.93 mmol) was slowly added to a mixed solution (1.2:1) of tetrahydrofuran (THF) and hexamethylphosphoramide (HMPA) of (10) (1.41 g, 8.42 mmol) cooled to -40°C, 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 raised to room temperature. Stirring was continued at the same temperature for 22 hours. Under ice cooling (at 4°C), 1N aqueous HCl solution and tBuMeO were added, followed by switching to NaHCO 3 The saturated solution was washed with saturated brine and further washed with anhydrous Na 2 SO 4 After drying, filtration, the solvent was distilled off under reduced pressure, and the residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) to obtain 1.28 g (11) (yield 46%). 1H NMR (400 MHz, chloroform-d) δ 4.55 (dd, 7 = 4.4, 2.8 Hz, 1H), 3.85 (ddd, 7 = 10.8, 7.6, 3.6 Hz, 1H), 3.71 (dt, 7 = 9.6, 6.8 Hz, 1H), 3.51-3.45 (m, 1H), 3.35 (dt, 7 = 9.6, 6.8 Hz, 1H), 3.34 (t, 7 =6.8Hz,2H),3.31(s,3H),2.14-2.08(m,4H),1.82(tdd,7=10.8,7.6,4.6Hz,1H),1.7 1(dt,7=12.8,2.8Hz,1H),1.63-1.40(m,10H),1.39-1.21(m,16H),0.90-0.79(m,4H).

[0196] Step 5: 19-Methoxynonadeca-10-yn-1-ol (12): To a solution of (11) (3.28 g, 8.31 mmol) in MeOH (0.6 M) was added p-TsOH (95 mg, 0.5 mmol). The reaction mixture was stirred at 60 °C for 3.5 days. The mixture was diluted with water, extracted with ether (2x), and washed with Na 2 SO 4 Dry, filter and remove the solvent in vacuo. The filtrate was concentrated to give 2.6 g (12) (yield > 99%). 1 H 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).

[0197] Step 6: 4-Methylbenzenesulfonic acid 19-methoxynonadeca-10-yn-1-ester (13): To a solution of (12) (2.6 g, 8.37 mmol) in DCM (0.5 M) at 0°C, 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 at room temperature for 6 h and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex: EtOAc 10: 1) to give 2.45 g (13) (yield 63%). HPLC-MS (Condition B): rt = 5.20 min; m / z: 465 [M+1] + ,482[M+23] + .

[0198] 4-Methylbenzenesulfonic acid 29-methoxynonacoustic-9,20-diynyl-l-ester (16):

[0199]

[0200] Step 1: 19-Bromo-1-methoxynonadeca-9-yne (14): A solution of lithium bromide (0.318 g, 3.66 mmol) in anhydrous THF (0.1 M) was dried over 3A molecular sieves (300 mg, previously activated at 400 °C for 24 hours) placed in a reaction flask. After stirring the solution for 20 minutes, a solution of (13) (0.85 g, 1.829 mmol) in anhydrous THF (2 mL + 2 mL) was added to the previous reaction flask. The solution was stirred under reflux for 4 h. The reaction mixture was then allowed to reach room temperature and diluted with tBuMeO. The organic layer was washed with saturated NaHCO 3 Wash with aqueous solution and use Na 2 SO 4 Dry, filter and remove the solvent under reduced pressure to give a yellow oil. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) to give 467 mg (14) (yield 68%). 1 H NMR (400MHz, chloroform-d) δ3.39(t,J=6.8Hz,2H),3.34(t,J=6.8Hz,2H),3.31(s,3H),2. 12(t,J=6.6Hz,4H), 1.83(q,J=7.2Hz,2H), 1.57-1.51(m,2H), 1.49-1.22(m,24H).

[0201] Step 2: 29-Methoxynonacoustic-9,20-diyn-1-ol (15): To a mixed solution of dec-9-yn-l-ol (230 mg, 1.48 mmol) in THF / HMPA (1.2:1) cooled to -40°C, a 1.6M n-BuLi solution in n-hexane (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 raised to room temperature. Stirring was continued at the same temperature for 22 hours. Under ice cooling (at 4°C), 1N HCl aqueous solution and tBuMeO were added, followed by switching to NaHCO 3 The saturated solution was washed with saturated brine and further washed with anhydrous Na 2 SO 4 After filtration, the solvent was distilled off under reduced pressure. The residue was purified by flash chromatography (silica gel + 5% AgNO 3 , Hex: EtOAc 4:1) to give 69.7 mg (15) (yield 12%). 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).

[0202] Step 3: 4-Methylbenzenesulfonic acid 29-methoxynonacoustic-9,20-diyn-1-ester (16): To a solution of (15) (69.7 mg, 0.156 mmol) in DCM (0.1 M) at 0°C, TEA (43 μL, 0.325 mmol), DMAP (3.3 mg, 0.027 mmol) and Ts-Cl (62 mg, 0.325 mmol) were added. The reaction mixture was then diluted with water and tBuMeO. The organic layer was washed with saturated NaHCO 3 The mixture was washed with aqueous solution and brine and then with Na 2 SO 4 Dry, filter and remove the solvent under reduced pressure to give a yellow oil. The residue was purified by flash chromatography (silica gel, Hex:EtOAc 10:1) to give 63.3 mg (16) (yield 67%). 1 H 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).

[0203] 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 at 40 °C for 4 h. The mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex: EtOAc 10: 1) to give 1.4 g (17) (34.5%). 1 H 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).

[0204] 3-Azidopropyl 4-methylbenzenesulfonate (18): To a solution of 3-azidopropan-l-ol (1 g, 9.89 mmol) in DCM (0.2 M) was added TEA (2.07 mL, 14.84 mmol) and Ts-Cl (2.26 g, 11.87 mmol) at 0°C. The reaction mixture was stirred at room temperature for 24 h, then quenched with water and washed with brine. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue was purified by flash chromatography (silica gel, Hex:EtOAc 4:1) to afford 1.27 g (18) (50%). 1 HNMR (400MHz, chloroform-d) δ7.80 (d, J=8.3Hz, 2H), 7.36 (dd, J=8.3, 0.7Hz, 2H), 4.1 1(t,J=6.3Hz,2H), 3.38(t,J=6.3Hz,2H), 2.46(s,3H), 1.89(p,J=6.3Hz,2H).

[0205] l-(5-bromopentyl)-1H-pyrazole (19): 1H-pyrazole (0.78 g, 11.49 mmol) and Cs 2 CO 3 To a mixture of (3.74 mg, 11.49 mmol) in acetonitrile (ACN, 57 mL) was added 1,5-dibromopentane (1.56 mL, 11.49 mmol). The mixture was stirred at room temperature for 18 h. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex: EtOAc 1:1) to give 1.1 g (19) (45%). HPLC-MS (Condition A): rt = 3.00 min; m / z: 218, 220 [M+1, M+3] + .

[0206] Benzyl pent-4-ynecarboxylate (20): A solution of pent-4-ynecarboxylic acid (5.02 g, 51.2 mmol) in DMF (102 mL) was treated with K 2 CO 3 (10.61 g, 77 mmol) and benzyl bromide (6.09 mL, 51.2 mmol), stirred for 72 h, then diluted with water (200 mL) and extracted with ether (3 x 150 mL). The combined organic extracts were dried (MgSO 4 ) and filtered. The solvent was removed in vacuo to give 9.9 g (20) (>99%). HPLC-MS (Condition A): rt = 3.70 min.

[0207] 4-Methylbenzenesulfonic acid 6-azidohexyl ester (22):

[0208]

[0209] 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 at 80 °C for 18 h. The reaction mixture was then quenched with water / EtOAc and washed with brine (3x). The organic layer was washed with Na 2 SO 4 Drying, filtration and concentration in vacuo afforded 470 mg (21) (>99%). 1 H 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).

[0210] Step 2: 4-Methylbenzenesulfonic acid 6-azidohexyl ester (22): 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) at 0°C. The reaction mixture was stirred at room temperature overnight. It was diluted with EtOAc and washed with 10% NaHSO 4 The aqueous phase was washed with 5% ethanol (3x). The combined layers were washed with saturated NaHCO 3 The aqueous solution was washed with anhydrous Na 2 SO 4 The solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel Hex: EtOAc 6:1) to give 666 mg (22) (62%). 1 H 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, 7 = 6.4 Hz, 2H), 1.55 (p, J = 6.4 Hz, 2H), 1.41-1.18 (m, 4H).

[0211] 2-Cyclopropylethyl 4-methylbenzenesulfonate (23): To a solution of 2-cyclopropylethanol (3 mL, 34.0 mmol) in DCM (85 mL) was added TEA (7.10 mL, 50.9 mmol) and Ts-Cl (7.77 g, 40.8 mmol), and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layers were washed with brine and washed with Na 2 SO 4 Dry and concentrate in vacuo.The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) to give 6.23 g (76%) of (23). 1 H 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).

[0212] 2-Cyclopentylethyl 4-methylbenzenesulfonate (24): To a solution of 2-cyclopentylethanol (1.09 mL, 8.76 mmol) in DCM (22 mL) was added TEA (1.83 mL, 13.1 mmol) and Ts-Cl (2.00 g, 10.5 mmol), and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layers were washed with brine and washed with Na 2 SO 4 Dry and concentrate in vacuo.The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) to give 1.53 g (65%) of (24). 1 H 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).

[0213] 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) was added TEA (1.26 mL, 9.02 mmol) and Ts-Cl (1.38 g, 7.22 mmol), and the obtained mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layers were washed with brine and washed with Na 2 SO 4 Dry and concentrate in vacuo.The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) to give 1.59 g (82%) (25). 1 H NMR (400MHz, chloroform-d) δ7.81(d,J=8Hz,2H),7.37(d,J=8Hz,2H),7.00(d,J=8.6Hz,2H),6.80(d,J=8.6Hz,2H),4.0 4(t,J=6Hz,2H),3.80(s,3H),2.61(dd,J=8.2,6.8Hz,2H),2.48(s,3H),2.03-1.86(ddt,J=8.2,6.8,6Hz,2H).

[0214] 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) was added TEA (1.02 mL, 7.35 mmol) and Ts-Cl (1.12 g, 5.88 mmol), and the resulting mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layers were washed with brine and washed with Na 2 SO 4 Dry and concentrate in vacuo.The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) to give 1.53 g (87%) of (26). 1 H NMR (400MHz, chloroform-d) δ7.63(d,J=8.5Hz,2H),7.28(d,J=7.8Hz,1H),7.21-7.16(m.2H),7.19(d,J=8.5Hz,2H),7.12 (,J=7.8Hz,1H),3.88(t,J=6.2Hz,2H),2.56(dd,8.0,7.6Hz,2H),2.29(s,3H),1.81(ddt,J=8.0,7.6,6.2Hz,2H).

[0215] 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) was added TEA (1.39 mL, 9.99 mmol) and Ts-Cl (1.52 g, 7.99 mmol), and the resulting mixture was stirred for 18 h. Water was added to the reaction mixture and extracted with DCM (2x). The combined organic layers were washed with brine and washed with Na 2 SO 4 Dry and concentrate in vacuo.The residue was purified by column chromatography on silica gel (Hex-EtOAc, 4:1) to give 1.85 g (87%) of (27). 1 H NMR (400MHz, chloroform-d) δ7.81(d,J=8.0Hz,2H),7.37(d,J=8.0Hz,2H),7.07(d,J=8.0Hz,2H),6.98(d,J=8.0Hz ,2H),4.05(t,J=6.4Hz,2H),2.62(t,J=7.5Hz,2H),2.48(s,3H),2.32(s,3H),1.95(tt,J=7.5,6.4Hz,2H).

[0216] 5-Acetamidopentyl 4-methylbenzenesulfonate (29):

[0217]

[0218] Step 1: N-(5-Hydroxypentyl)acetamide (28): To a solution of 5-aminopentan-l-ol (50 g, 485 mmol) and 2,5-dioxopyrrolidin-l-yl acetate (75 g, 485 mmol) in dimethylformamide (DMF, 0.5 M) was added TEA (101 mL, 727 mmol) and the solution was stirred at 60 °C for 18 h. Then, the solvent was evaporated by high vacuum rotary evaporator and the residue was dissolved in MeOH and treated with IRA-410 until basic pH (about 10), filtered and evaporated to dryness to give 70.4 g (28) (100%). The crude product was used without further purification. 1 H NMR (400MHz, CD 3 OD) δ3.57(t,J=6.5Hz,2H),3.18(t,J=7.0Hz,2H),1.94(s,3H),1.65-1.47(m,4H),1.49-1.32(m,2H).

[0219] Step 2: 5-Acetylaminopentyl 4-methylbenzenesulfonate (29):To a solution of (28) (70.4 g, 485 mmol) in DCM (0.5 M) was added TEA (101 mL, 727 mmol) and Ts-Cl (92 g, 485 mmol). The reaction mixture was stirred at room temperature for 18 h, then quenched with water / DCM and treated with saturated NaHCO 3 The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to afford 92.45 g (29) (63%). 1 H NMR (400 MHz, chloroform-d): δ7.84-7.74 (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] + .

[0220] (((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).

[0221] 5-(Benzyloxy)pentyl 4-methylbenzenesulfonate (35): To a solution of 5-(benzyloxy)pentan-l-ol (11.2 g, 57.7 mmol) in dichloromethane (DCM, 0.4 M) at 0°C was added triethylamine (TEA, 12 mL, 86 mmol) and Ts-Cl (11 g, 57.7 mmol). The reaction mixture was stirred at room temperature for 18 h and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, Hex / OEtAc (4:1)) to give 15.32 g (35) (yield 76%). HPLC-MS (Condition A): rt = 4.55 min; m / z: 349 [M+1] + ,371[M+23] +

[0222]

[0223] 4-Methylbenzenesulfonic acid 5-azidopentyl ester (37)

[0224] Step 1: 5-Azidopentan-1-ol (36):A solution of 5-bromopentan-l-ol (0.10 mL, 0.89 mmol) and sodium azide (63 mg, 0.98 mmol) in dimethylformamide (DMF, 0.2 M) was stirred at 80 °C for 18 h. The reaction mixture was then quenched with water / EtOAc and washed with brine (3x). The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to afford 57 mg (36) (50%). 1 H NMR (400MHz, chloroform-d) δ3.63 (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).

[0225] 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) was added TEA (87 μL, 0.63 mmol) and Ts-Cl (80 mg, 0.42 mmol) at 0°C. The reaction mixture was stirred at room temperature for 60 h, then quenched with water / DCM and washed with brine. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to obtain 92 mg (37) (78%). HPLC-MS (Condition A): rt = 3.00 min; m / z: 284 [M+1] + .

[0226] Methyl 3-azidopropionate (38): A mixture of methyl 3-bromopropionate (10.70 ml, 98 mmol) and sodium azide (8.92 g, 137 mmol) was dissolved in DMSO (volume: 49.0 ml). The solution was heated to 45 °C and stirred for 18 h. After the mixture was cooled to room temperature, it was extracted with ether. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated on a rotary evaporator to give azidopropionate as a colorless liquid. 1 H 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).

[0227] B. General Procedures

[0228] Bl Alkylation Procedure

[0229] Procedure A: To a solution of (2), (3), (4), (33) or (34) (1 eq) in dimethylformamide (DMF, 0.2 M) was added sodium hydride (2.15 eq) at 0°C. When the addition was complete, the mixture was stirred at room temperature for 5 minutes. Finally, the alkylating agent was added. The reaction was stirred overnight and then quenched with water and extracted with EtOAc. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0230] Procedure B: To a solution of (2), (3), (4), (33) or (34) (1 eq) in DMF (c = 0.15 M) was added sodium hydride (1.2 eq) at 0°C. When the addition was complete, the mixture was stirred at room temperature for 5 min. Finally, the alkylating agent was added. The reaction was stirred overnight and then quenched with water and extracted with EtOAc. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0231] Procedure N: To a solution of (2), (3), (4), (33) or (34) (1 eq) in DMF (0.2 M) was added LiH at 0°C. When the addition was complete, the mixture was stirred at room temperature for 5 minutes. Finally, the alkylating agent was added. The reaction was stirred for different times and temperatures depending on the alkylating agent, then quenched with water and extracted with EtOAc. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0232] B.2. Debenzylation procedure

[0233] Procedure K: Alkyl-inositol derivatives (II_B', II_C, VIII_B' or IX_D) were dissolved in a mixture of THF / MeOH (7:3, 0.05 M), followed by the addition of excess palladium hydroxide on carbon. The mixture was placed under a hydrogen atmosphere and stirred at room temperature for 2 days. The mixture was then purged with nitrogen, filtered and concentrated to give the desired compound.

[0234] B.3. Hydrolysis procedure

[0235] Procedure C: Alkyl-inositol derivatives (II_A, II_B, II_B', II_D, V_A, V_B, V_D or VIII-B) were dissolved in a mixture of MeOH / water / DCM / trifluoroacetic acid (3:1:1:1, 0.1 M) and the solution was stirred at room temperature overnight. Finally, the solvent and excess TFA were removed under vacuum to obtain the desired compound.

[0236] Procedure D: Alkyl-inositol derivatives (II_A, II_B, II_B', II_D, V_A, V_B, V_D or VIII-B) were dissolved in a mixture of MeOH / water / DCM / trifluoroacetic acid (3:1:1:1, 0.1 M) and the solution was stirred at room temperature overnight. Then, the solvent and excess TFA were removed under vacuum. Finally, the residue was dissolved in MeOH, treated with IRA-400 resin until the pH was basic, filtered and the solvent was removed under vacuum to obtain the desired compound.

[0237] Procedure E: To a solution of alkyl-inositol derivatives (II_A or V_A) in tetrahydrofuran (THF) (c=0.1 M) was added a 0.1 M solution of TBAF in THF (1.2 eq). The reaction mixture was stirred at room temperature for 18 h, quenched with water and extracted with EtOAc. The organic layer was washed with Na 2 SO 4 The residue was dried, filtered and concentrated in vacuo. The residue was dissolved in a mixture of MeOH / water / DCM / trifluoroacetic acid (3:1:1:1, 0.1 M) and the solution was stirred at room temperature overnight. The solvent and excess TFA were then removed under vacuum. Finally, the residue was dissolved in MeOH (MeOH), treated with IRA-400 resin until the pH was basic, filtered and the solvent was removed under vacuum to obtain the desired compound.

[0238] Procedure F: Alkyl-inositol derivatives (II_A, II_B, II_B', II_D, V_A, V_B, V_D or VIII-B) were dissolved in a mixture of DCM / trifluoroacetic acid (4:1, 0.14 M) and the solution was stirred at room temperature for 1 h. Then, water (final concentration 0.1 M) was added and the reaction mixture was stirred at room temperature for 18 h. Finally, the layers were separated and the aqueous layer was concentrated in vacuo to obtain the desired compound.

[0239] Procedure S: Alkyl-inositol derivatives (II_A, II_B, II_B', II_D, V_A, V_B, V_D or VIII-B) were dissolved in a mixture of MeOH / HCl 1N (10:1, 0.1 M) and the solution was stirred at room temperature or 60°C for 48 h. Finally, the solvent and excess HCl were removed under vacuum. Finally, the residue was dissolved in MeOH, treated with IRA-400 resin until the pH was basic, filtered and the solvent was removed under vacuum to obtain the desired compound.

[0240] B.4. Click reaction procedure

[0241] Procedure M: To intermediate (VI_A, V_C or X_D) (1 eq), CuSO 4 ·5H 2 To a solution of 1H-1H-2O (0.4 eq) and sodium ascorbate (0.6 eq) in a mixture of water (0.07 M) was added a solution of the alkynyl reagent in THF (0.35 M). The reaction mixture was stirred at room temperature at 60 ° C under an inert atmosphere for 24 h, filtered on celite and concentrated in vacuo. The residue was dissolved in MeOH, treated with IRA-400 resin until the pH was basic, filtered and the solvent was removed in vacuo to give the desired compound.

[0242] Procedure L: To intermediate (III_B or IX_D) (1 eq), CuSO 4 ·5H 2 To a solution of 1H 2 O (0.4 eq) and sodium ascorbate (0.6 eq) in water (0.07 M) was added a solution of azide reagent (2 eq) in THF (0.35 M). The reaction mixture was stirred at room temperature under an inert atmosphere for 20 h, filtered on celite and concentrated in vacuo. The residue was treated with water / DCM. The organic layer was then washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to give the desired compound.

[0243] B.5. Azide Reduction Procedure

[0244] Procedure P: To a solution of intermediate (V_B or X_D) (1 eq) in a mixture of THF / water (9:1, 0.08 M) was added DIPEA (3 eq) and PPh 3 (2.6 eq). The reaction mixture was stirred at 60 °C for 4 h, then quenched with water and washed with brine. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to give the desired compound without further purification.

[0245] B.6. Amide Formation Procedure

[0246] Procedure Q: To a solution of intermediate (II_A, III_B or IX_D) (1 eq) in DMF (0.1 M) was added TEA (4 eq) and activated acid (2 eq). The reaction mixture was stirred at room temperature for 4 h and concentrated in vacuo. The residue was dissolved in MeOH, treated with IRA-400 resin until the pH was alkaline, filtered and the solvent was removed under vacuum. Finally, the residue was purified by flash chromatography (silica gel) to obtain the pure compound.

[0247] B.5. Phosphorylation Procedure

[0248] Procedure G: Alkyl-inositol derivative (III_A, VI_A, III_B, III_C or III_D) (1 eq) was dissolved in DCM (0.02 M) and a solution of tetrazole (14.4 eq) in ACN (0.43 M) was added. The mixture was stirred at room temperature for 30 min. Then N,N-diethyl-l,5-dihydrobenzo[e][l,3,2]-dioxophosphinami-3-amine (7.2 eq) was added and stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0°C and a solution of tert-butyl hydroperoxide (19.2 eq) in hexane (5.5 M) was added. The solution was brought to room temperature and stirred for 1 h. The mixture was washed with dilute sodium sulfite and extracted with DCM. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0249] Procedure H: Alkyl-inositol derivatives (III_A, VI_A, III_B, III_C or III_D) (1 eq) were dissolved in DCM (0.02 M) and a solution of tetrazole (18 eq) in ACN (0.43 M) was added. The mixture was stirred at room temperature for 30 min. Then, N,N-diethyl-l,5-dihydrobenzo[e][l,3,2]-dioxophosphinami-3-amine (9 eq) was added and stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0 °C and a solution of tert-butyl hydroperoxide (24 eq) in hexane (5.5 M) was added. The solution was brought to room temperature and stirred for 1 h. The mixture was washed with dilute sodium sulfite and extracted with DCM. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0250] Procedure R: Alkyl-inositol derivative (III_A, VI_A, III_B, III_C or III_D) (1 eq) was dissolved in DMF (0.05 M) and a solution of phenyltetrazolyl (18 eq) in DMF (5 M) was added. The mixture was stirred at room temperature for 30 min. Then, N,N-diethyl-l,5-dihydrobenzo[e][l,3,2]-dioxophosphinami-3-amine (9 eq) was added and stirred at room temperature overnight. Finally, the reaction mixture was cooled at 0 °C and a solution of tert-butyl hydroperoxide (24 eq) in hexane (5.5 M) was added. The solution was brought to room temperature and stirred for 1 h. The mixture was washed with dilute sodium sulfite and extracted with EtOAc (x2). The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo.The residue is purified by flash chromatography (silica gel) to give the pure compound.

[0251] B.6. Phosphate Deprotection Procedure

[0252] Procedure I: The 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, 0.01 M), followed by the addition of excess palladium hydroxide on carbon or palladium on carbon. The mixture was placed under a hydrogen atmosphere and stirred at room temperature for 2 days. The mixture was then purged with nitrogen, filtered and concentrated. The compound was brought to pH 7 by adding a dilute aqueous NaOH solution (1 N) and the residue was purified on a sephadex column (PD-10, G-25-M) by eluting with water. All fractions were lyophilized and purified by 1 H-NMR analysis. The product containing fractions were further purified by elution with water on a reverse phase column (Sep-Pack, Waters, 1 g, C18). All fractions were lyophilized and separated by 1 H-NMR analysis.

[0253] Procedure J: The 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 the addition of excess palladium hydroxide on carbon or palladium on carbon. The mixture was placed under a hydrogen atmosphere and stirred at room temperature for 2 days. The mixture was then purged with nitrogen, filtered and concentrated. The compound was brought to pH 10 by adding a dilute aqueous NaOH solution (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 purified by 1 H-NMR analysis. The product containing fractions were further purified by elution with water on a reverse phase column (Sep-Pack, Waters, 1 g, C18). All fractions were lyophilized and separated by1 H-NMR analysis.

[0254] Procedure T: The phosphorylated compound (IV_A, VII-A, IV_B, IV_C or IV_D) was treated with a solution of thiophenol (40 eq) and meta-cresol (40 eq) in TFA (0.045 M). Then TBMSBr (40 eq) was slowly added and the mixture was stirred at room temperature for 4 h, quenched with water, and extracted with DCM (3x). The aqueous layer was concentrated in vacuo. The residue was brought to pH 9-10 by adding water and a dilute aqueous NaOH solution (1 N), and the compound was purified on a sephadex column (PD-10, G-25-M) by eluting with water. All fractions were lyophilized and purified by 1 H-NMR analysis. The product containing fractions were further analyzed by reverse phase column (Sep- C18 cartridge, 1 g, Waters Corp., Milford, MA, USA) and purified by elution with water. All fractions were lyophilized and purified by 1 H-NMR analysis.

[0255] C. Synthesis of Intermediates II-X

[0256] C.1. Intermediates II_A, II_B, II_B', II_C and II_D

[0257] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-pentyl-myo-inositol (II_A-1): According to the general alkylation procedure A, 48 mg (II_A-1) (yield 13%) was obtained from 377 μL (3 eq) 1-bromopentane. HPLC-MS (condition A): rt = 4.90 min; m / z: 375 [M+1] + .

[0258] rac-4-O-(5-(benzyloxy(pentyl)-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-myo-inositol (II_A-2): According to the general alkylation procedure A, 183 mg (II_A-2) was obtained from 1.04 mL (3 eq) (((5-bromopentyl)oxy)methyl)benzene (yield 22.8%). HPLC-MS (condition A): rt = 4.99 min; m / z: 481 [M+1] + ,503[M+23] + .

[0259] rac-2-O-tert-butyldimethylsilyl-4-O-(5-methoxypentyl)-l,3,5-O-methy-myo-inositol (II_A-3): According to the general alkylation procedure A, 26 mg (II_A-3) (yield 11%) was obtained from 241 mg (2.2 eq, in 3 mL DMF) of l-bromo-5-methoxypentane. HPLC-MS (condition B): rt = 3.22 min; m / z: 405 [M+1] + .

[0260] rac-2-O-tert-butyldimethylsilyl-4-O-(5-ethoxycarbonylpentyl)-l,3,5-O-methy-myo-inositol (II_A-4): According to the general alkylation procedure A, 107 mg (II_A-4) (yield 36%) was obtained from 351 μL 6-bromohexanoic acid ethyl ester (3 eq). HPLC-MS (condition A): rt = 4.99 min; m / z: 447 [M+1] + .

[0261] rac-4-O-(2-(4-acetylpiperazin-1-yl)ethyl)-2-O-tert-butyldimethylsilyl-1,3,5-O-methy1-myo-inositol (II_A-5): According to the general alkylation procedure A, 460 mg (II_A-5) (yield 68%) was obtained from 700 mg (2.5 eq in 7.3 mL DMF) of (5) (2.5 eq in 7.3 mL DMF). HPLC-MS (condition A): rt = 1.90 min; m / z: 459 [M+1] + .

[0262] 4,6-Bis-O-(4-methoxybenzyl)-l,3,5-O-methylene-2-O-pentyl-myo-inositol (II_B-1): According to the general alkylation procedure B, 142 mg (II_B-1) (yield 61%) was obtained from 200 mg (3) and 87 μL (1.5 eq) of 1-bromopentane. HPLC-MS (condition B): rt = 3.43 min; m / z: 501 [M+1] + ,523[M+23] + .

[0263] 4,6-Bis-O-(4-methoxybenzyl)-2-O-(5-methoxypentyl)-l,3,5-O-methylene-myo-inositol (II_B-2): According to the general alkylation procedure B, 180 mg (II_B-2) (yield 36.5%) was obtained from 400 mg (3) and 505 mg (3 eq) of l-bromo-5-methoxypentane. HPLC-MS (condition A): rt = 4.26 min; m / z: 531 [M+1]+ ,553[M+23] + .

[0264] 4,6-Bis-O-(4-methoxybenzyl)-2-O-(9-methoxynonyl)-l,3,5-O-methylene-myo-inositol (II_B-3): According to the general alkylation procedure B, 430 mg (II_B-3) was obtained from 500 mg (3) and 420 mg (1.1 eq) (7) (yield 63%). 1 H NMR (400MHz, chloroform-d) δ7.20(d,J=8.6Hz,4H),6.82(d,J=8.6Hz,4H),5.48(d,J=1.2Hz ,1H),4.60(d,J=11.3Hz,2H),4.47(d,J=11.3Hz,2H),4.38-4.35(m,1H),4.30(t,J =3.6Hz,2H),4.24-4.22(m,2H),3.82(q,J=1.6Hz,1H),3.79(s,6H),3.47(t,J=6.8 Hz, 2H), 3.34 (t, J = 6.8Hz, 2H), 3.31 (s, 3H), 1.64-1.50 (m, 8H), 1.33-1.21 (m, 6H).

[0265] 4,6-Di-O-benzyl-2-O-(19-methoxynonadeca-10-yn-1-yl)-1,3,5-O-methylene-myo-inositol (II_B'-1): According to the general alkylation procedure B, 504 mg (II_B'-1) was obtained from 437 mg (4) and 631 mg (1.1 eq) (13) (yield 66%). 1 H NMR (400 MHz, chloroform-d) δ7.28 (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=6.8Hz,2H),3.34(t,J=6.8Hz,2H),3.31(s,3H),2.11(t,7=7.0Hz,4H ),1.60(q,7=7.0Hz,2H),1.54-1.51(m,2H),1.44(q,7=7.0Hz,4H),1.37-1.24(m,16H).

[0266] 4,6-Di-O-benzyl-2-O-(29-methoxynonacoustic-9,20-diyn-1-yl)-1,3,5-O-methylene-myo-inositol (II_B'-2): According to the general alkylation procedure B, 776 mg (II_B'-2) was obtained from 404 mg (4) and 721 mg (1.1 eq) (16) (yield 89%). 1 H NMR (400 MHz, chloroform-d) δ7.28 (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=6.8Hz,2H),3.34(t,J=6.8Hz,2H),3.31(s,3H),2.11(t,7=7.2Hz,8H ),1.61(p,J=6.9Hz,2H),1.55-1.50(m,2H),1.45(p,J=7.0Hz,8H),1.38-1.25(m,26H).

[0267] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-(3-(p-tolyl)propyl)-myo-inositol (II_A-6): According to the general alkylation procedure N, 374 mg (II_A-6) was obtained from 1.848 g (2.5 eq.) (27) (yield 35%). HPLC-MS (condition A): rt = 4.99 min; m / z: 437 [M+1] + ,459[M+23] + .

[0268] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-(4-methylpentyl)-myo-inositol (II_A-7): According to the general alkylation procedure N, 781 mg (II_A-7) (yield 71%) was obtained from 1 mL (2.5 eq.) 1-bromo-4-methylpentane. HPLC-MS (condition A): rt = 5.09 min; m / z: 389 [M+1] + ,411[M+23] + .

[0269] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-(6,6,6-trifluorohexyl)-myo-inositol (II_A-8): According to the general alkylation procedure N, 574 mg (II_A-8) (yield 61%) was obtained from 1.158 g (2.5 eq.) 6-bromo-1,1,1-trifluorohexane. HPLC-MS (condition A): rt = 4.73 min; m / z: 443 [M+1] + ,465[M+23] + .

[0270] rac-2-O-tert-butyldimethylsilyl-4-O-(3-(4-methoxyphenyl)propyl)-1,3,5-O-methy-myo-inositol (II_A-9): According to the general alkylation procedure N, 457 mg (II_A-9) (yield 51%) was obtained from 1.59 g (2.5 eq.) (25). HPLC-MS (condition A): rt = 4.72 min; m / z: 453 [M+1] + ,455[M+23] + .

[0271] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-(3-(3-(trifluoromethyl)phenyl)propyl)-myo-inositol (II_A-10): According to the general alkylation procedure N, 807 mg (II_A-10) (yield 96%) was obtained from 1.53 g (2.5 eq.) (26). HPLC-MS (condition A): rt = 4.99 min; m / z: 491 [M+1] + .

[0272] rac-2-O-tert-butyldimethylsilyl-4-O-(2-cyclopentylethyl)-1,3,5-O-methy-myo-inositol (II_A-11): According to the general alkylation procedure N, 50 mg (II_A-11) was obtained from 1.53 g (2.5 eq.) (24) (yield 5%). HPLC-MS (condition A): rt = 5.26 min; m / z: 401 [M+1] + ,423[M+23] + .

[0273] rac-2-O-tert-butyldimethylsilyl-4-O-(2-cyclopropylethyl)-1,3,5-O-methy-myo-inositol (II_A-12): According to the general alkylation procedure A, 552 mg (II_A-12) was obtained from 1.45 g (1 eq.) (23) (yield 25%). HPLC-MS (condition A): rt = 4.65 min; m / z: 373 [M+1] +,395[M+23] + .

[0274] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-(5-(IH-pyrazol-l-yl)pentyl)-myo-inositol (II_A-13): According to the general alkylation procedure A, 174 mg (II_A-13) was obtained from 214 mg (19) (yield 60%). HPLC-MS (condition A): rt = 4.11 min; m / z: 441 [M+1] + .

[0275] rac-4-O-(5-acetamidopentyl)-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-myo-inositol (II_A-14): According to the general alkylation procedure N, 241 mg (II_A-14) (yield 50%) was obtained from 1 g (3 eq.) (29). HPLC-MS (condition A): rt = 3.78 min; m / z: 432 [M+1] + .

[0276] rac-2-O-tert-Butyldimethylsilyl-4-O-(10-ethoxycarbonyldecyl)-1,3,5-O-methyI-myo-inositol (II_A-15): According to the general alkylation procedure A, 50 mg (II_A-15) was obtained from 500 mg (2.5 eq.) of 11-bromodencanoic acid ethyl ester (yield 14%). 1 H NMR (400MHz, chloroform-d) δ5.47(d,J=1.6Hz,1H),4.39(ddt,J=10.1,4.1,2.8Hz,1H),4.24(t,7=2.8Hz,2H),4 .18(dt,J=5.2,2.1Hz,1H),4.14(q,J=1.6Hz,1H),4.11-4.08(m,1H),4.09(q,J=7.1Hz,1H),3.70(d,J=1 0.1Hz,1H),3.59(td,J=9,5,6.5Hz,1H),3.58(td,J=9,5,6.5Hz,1H),2.25(t,J=7.6Hz,2H),1.58(p,J= 6.8Hz, 2H), 1.55 (p, J = 6.8Hz, 2H), 1.30-1.23 (m, 12H), 1.22 (t, J = 7.1Hz, 3H), 0.92 (s, 9H), 0.13 (s, 6H).

[0277] rac-4-O-(10-(Benzyloxy)decyl)-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-myo-inositol (II_A-16): According to the general alkylation procedure A, 44.5 mg (II_A-16) was obtained from 407.9 mg (2.1 eq.) (30) (yield 14%). HPLC-MS (condition A): rt = 6.13 min; m / z: 551 [M+1] + .

[0278] rac-2-O-tert-butyldimethylsilyl-4-O-methyl-1,3,5-O-methy1-myo-inositol (II_A-17): According to the general alkylation procedure A, 50 mg (II_A-17) (yield 10%) was obtained from 0.1 mL (1 eq.) iodomethane. HPLC-MS (condition A): rt = 3.83 min; m / z: 319 [M+1] + ,341[M+23] + .

[0279] rac-2-O-tert-butyldimethylsilyl-4-O-(7-methoxyheptyl)-1,3,5-O-methylene-myo-inositol (II_A-18): According to the general alkylation procedure A, 163 mg (II_A-18) (yield 25%) was obtained from 780 mg (2.5 eq.) (17). HPLC-MS (condition A): rt = 4.79 min; m / z: 433 [M+1] + ,455[M+23] + .

[0280] rac-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-4-O-propyl-myo-inositol (II_A-19): According to the general alkylation procedure A, 139 mg (II_A-19) (yield 41%) was obtained from 481 μL (5 eq.) 1-iodopropane. HPLC-MS (condition A): rt = 4.41 min; m / z: 347 [M+1] + ,369[M+23] + .

[0281] l,2,3,4,6-penta-O-benzyl-5-O-propargyl-myo-inositol (II_C-1): According to the general alkylation procedure B, 107 mg (II_C-1) (yield 50%) was obtained from 200 mg (33) and 141 μL of toluene containing 3-bromoprop-1-yne (3 eq, 80%). HPLC-MS (condition A): rt = 5.98 min; m / z: 670 [M+1] + ,692[M+23] + .

[0282] l,2,3,4,6-penta-O-benzyl-5-O-(2-cyclopropylethyl)-myo-inositol (II_C-2): According to the general alkylation procedure B, 108 mg (II_C-2) (yield 49%) was obtained from 200 mg (33) and 114 mg (1.5 eq) (23). HPLC-MS (condition A): rt = 6.56 min; m / z: 700 [M+1] + ,722[M+23] + .

[0283] l,2,3,4,6-penta-O-benzyl-5-O-(9-methoxynonyl)-myo-inositol (II_C-3): According to the general alkylation procedure B, 127 mg (II_C-3) (yield 51%) was obtained from 200 mg (33) and 156 mg (1.5 eq) (7). HPLC-MS (condition A): rt = 7.11 min; m / z: 789 [M+1] + ,810[M+23] + .

[0284] Rac-2,4,6-tri-O-benzyl-3,5-O-ethylidene-lO-propargyl-myo-inositol (II_D-1): According to the general alkylation procedure B, 146 mg (II_C-1) (yield 83%) was obtained from 162 mg (34) and 152 μL of toluene containing 3-bromoprop-l-yne (3 eq, 80%). HPLC-MS (condition A): rt = 5.08 min; m / z: 537 [M+23] + .

[0285] Rac-2-O-tert-butyldimethylsilyl-4-O-(5-carboxypentyl)-l,3,5-O-methylene-myo-inositol (II_A-20): To a solution of intermediate (II_A-4) (1.58 g, 3.56 mmol) in MeOH / THF (0.15 M) was added a solution of lithium hydroxide (1 M, 11 mL, 10.96 mmol) and the solution was stirred at room temperature for 18 h, then quenched with HCl 1 M / DCM and washed with brine. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo. The residue was purified by flash chromatography (silica gel, Hex / EtOAc 1:1) to give 575 mg (II_A-20) (38%). HPLC-MS (Condition A): rt = 3.91 min; m / z: 419 [M+1] + .

[0286] Rac-4-O-(6-amino-6-oxohexyl)-2-O-tert-butyldimethylsilyl-l,3,5-O-methy1-myo-inositol (II_A-21): To a mixture of intermediate (II_A-20) (80 mg, 0.19 mmol), TEA (53 μL, 0.38 mmol) and bis(2,5-dioxopyrrolidin-l-yl) carbonate (59 mg, 0.23 mmol) in DCM (0.15 M) was added a solution of ammonia in dioxane (2.8 mL, 1.91 mmol), and the solution was stirred at room temperature for 18 h, then quenched with water / DCM and washed with brine. The organic layer was washed with Na 2 SO 4 Dry, filter and concentrate in vacuo to obtain 72 mg (II_A-21) (90%). HPLC-MS (Condition A): rt = 3.66 min; m / z: 418 [M+1] + .

[0287] 4,6-Bis-O-(4-methoxybenzyl)-2-O-propargyl-myo-inositol (II_B-4): According to the general alkylation procedure A, 184 mg (II_B-4) (yield 68%) was obtained from 248 mg (3) and 171 mg (2 eq) propargyl bromide. HPLC-MS (condition A): rt = 4.07 min; m / z: 469 [M+1] + .

[0288] 2-O-(5-(Benzyloxy)pentyl)-4,6-bis-O-(4-methoxybenzyl)-l,3,5-O-methylene-myo-inositol (II_B-5): According to the general alkylation procedure A, 179 mg (II_B-5) was obtained from 162 mg (3) and 262 mg (2 eq) (35) (yield 78%). HPLC-MS (condition A): rt = 4.90 min; m / z: 607 [M+1] + ,629[M+23] + .

[0289] 2-O-(5-aminopentyl)-4,6-bis-O-(4-methoxybenzyl)-l,3,5-O-methylin-myo-inositol (II_B-6): According to the general azide reduction procedure P, 203 mg (II_B-6) (100%) was obtained from 110 mg (V_B-1). HPLC-MS (condition A): rt = 3.24 min; m / z: 516 [M+1] + .

[0290] 4,6-Bis-O-(4-methoxybenzyl)-2-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-1,3,5-O-methylin-myo-inositol (II_B-7): According to the general click reaction procedure M, 142 mg (II_B-7) (100%) was obtained from 126 mg (V_B-1) and 16 mg (1 eq.) 3-methoxyprop-1-yne. HPLC-MS (condition A): rt = 3.97 min; m / z: 612 [M+1] + .

[0291] 4,6-Di-O-benzyl-2-O-(6,6,6-trifluorohexyl)-O-1,3,5-methy1-myo-inositol (II_B'-3): According to the general alkylation procedure B, 89.9 mg (II_B'-3) (yield 33%) was obtained from 200 mg (4) and 142 mg (1.2 eq) 6-bromo-1,1,1-trifluorohexane. HPLC-MS (condition A): rt = 4.90 min; m / z: 509 [M+1] + ,532[M+23] + .

[0292] 2-O-(6-amino-6-oxohexyl)-4,6-di-O-benzyl-1,3,5-O-methy1-myo-inositol (II_B'-4): According to the general alkylation procedure B, 70 mg (II_B'-4) (yield 27%) was obtained from 200 mg (4) and 126 mg (1.2 eq) 6-bromohexanamide. HPLC-MS (condition A): rt = 3.75 min; m / z: 484 [M+1] + .

[0293] 4,6-Di-O-benzyl-2-O-(2-cyclopentylethyl)-1,3,5-O-methylene-myo-inositol (II_B'-5): According to the general alkylation procedure B, 184 mg (II_B'-5) (yield 83%) was obtained from 175 mg (4) and 152 mg (1.2 eq) (24). HPLC-MS (condition A): rt = 5.20 min; m / z: 467 [M+1] + .

[0294] 4,6-Di-O-benzyl-2-O-(2-cyclopropylethyl)-l,3,5-O-methylene-myo-inositol (II_B'-6): According to the general alkylation procedure B, 230 mg (II_B'-6) was obtained from 200 mg (4) and 195 mg (1.5 eq) (23) (yield> 99%). HPLC-MS (condition A): rt = 4.74 min; m / z: 439 [M+1] +,461[M+23] + .

[0295] 1,2,3,4,6-penta-O-benzyl-5-O-(5-methoxypentyl)-myo-inositol (II_C-4): According to the general alkylation procedure A, 46 mg (II_C-4) (yield 16%) was obtained from 250 mg (33) and 144 mg (1.5 eq) 1-bromo-5-methoxypentane. HPLC-MS (condition A): rt = 6.36 min; m / z: 732 [M+1] + ,754[M+23] + .

[0296] 1,2,3,4,6-penta-O-benzyl-5-O-(6,6,6-trifluorohexyl)-myo-inositol (II_C-5): According to the general alkylation procedure A, 162 mg (II_C-5) (yield 53%) was obtained from 250 mg (33) and 174 mg (2 eq) 6-bromo-1,1,1-trifluorohexane. HPLC-MS (condition A): rt = 6.38 min; m / z: 770 [M+1] + ,792[M+23] + .

[0297] 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 the general click reaction procedure M, 102 mg (II_C-6) (85%) was obtained from 110 mg (V_C-1) and 21 mg (2 eq.) 3-methoxyprop-1-yne. HPLC-MS (condition A): rt = 5.59 min; m / z: 813 [M+1] + .

[0298] Rac-2,4,6-tri-O-benzyl-3,5-O-ethylidene-1O-(9-methoxynonyl)-myo-inositol (II_D-2): According to the general alkylation procedure B, 270 mg (II_D-2) was obtained from 203 mg (34) and 210 mg (1.5 eq) (7) (yield> 99%). HPLC-MS (condition A): rt = 6.06 min; m / z: 656 [M+23] + .

[0299] Rac-2,4,6-tri-O-benzyl-1O-(2-cyclopropylethyl)-3,5-O-ethylidene-myo-inositol (II_D-3): According to the general alkylation procedure B, 246 mg (II_D-3) was obtained from 215 mg (34) and 163 mg (1.5 eq) (23) (yield> 99%). HPLC-MS (condition A): rt = 5.53 min; m / z: 568 [M+23] + .

[0300] Rac-2,4,6-tri-O-benzyl-3,5-O-ethylidene-2-O-propargyl-myo-inositol (II_D-4): According to the general alkylation procedure A, 232 mg (II_D-4) (yield> 99%) was obtained from 215 mg (34) and 201 mg (3 eq) propargyl bromide. HPLC-MS (condition A): rt = 4.97 min; m / z: 537 [M+23] + .

[0301] Rac-2,4,6-tri-O-benzyl-3,5-O-ethylidene-1O-(6,6,6-trifluorohexyl)-myo-inositol (II_D-5): According to the general alkylation procedure A, 107 mg (II_D-5) (yield 33%) was obtained from 250 mg (34) and 230 mg (2 eq) 6-bromo-1,1,1-trifluorohexane. HPLC-MS (condition A): rt = 5.62 min; m / z: 637 [M+23] + .

[0302] Rac-2,4,6-tri-O-benzyl-1O-(2-cyclopentylethyl)-3,5-O-ethylidene-myo-inositol (II_D-6): According to the general alkylation procedure A, 124 mg (II_D-6) (yield 41%) was obtained from 250 mg (34) and 211 mg (1.5 eq) (24). HPLC-MS (condition A): rt = 6.06 min; m / z: 596 [M+23] + .

[0303] C.2. Intermediates III_A, III_B, III_C and III_D

[0304] rac-4-O-pentyl-myo-inositol (III_A-1): According to the general hydrolysis procedure E, 16.6 mg (III_A-1) was obtained from 48 mg (II_A-1) (yield 53%).

[0305] rac-4-O-(5-(Benzyloxy)pentyl)-myo-inositol (III_A-2): According to the general hydrolysis procedure C, 20.71 mg (III_A-2) was obtained from 48 mg (II_A-2) (yield 58%). HPLC-MS (condition B): rt = 1.83 min; m / z: 357 [M+1] + .

[0306] rac-4-O-(5-methoxypentyl)-myo-inositol (III_A-3): According to the general hydrolysis procedure C, 12.3 mg (III_A-3) was obtained from 26 mg (II_A-3) (yield 68%). HPLC-MS (condition B): rt = 0.53 min; m / z: 281 [M+1] + ,303[M+23] + .

[0307] Rac-4-O-(5-methoxycarbonylpentyl)-myo-inositol (III_A-4): According to the general hydrolysis procedure C, with slight modification (aqueous workup), 42 mg (III_A-4) (yield 61%) was obtained from 100 mg (II_A-4). HPLC-MS (condition B): rt = 0.92 min; m / z: 309 [M+1] + .

[0308] rac-4-O-(2-(4-acetylpiperazin-l-yl)ethyl)-myo-inositol (III_A-5): According to the general hydrolysis procedure C, 24 mg (III_A-5) was obtained from 38 mg (II_A-5) (yield 86%). HPLC-MS (condition B): rt = 0.23 min; m / z: 335 [M+1] + .

[0309] 2-O-pentyl-myo-inositol (III_B-1): According to the general hydrolysis procedure F, 55.5 mg (III_B-1) was obtained from 127 mg (II_B-1) (yield 87%). HPLC-MS (condition A): rt = 1.65 min; m / z: 251 [M+1] + ,273[M+23] + .

[0310] 2-O-(5-Methoxypentyl)-myo-inositol (III_B-2): According to the general hydrolysis procedure F, 84 mg of (III_B-2) was obtained from 180 mg of (II_B-2) (yield 88%). 1 H NMR (400 MHz, MeOH-d 4)δ374(t,J=6.4Hz,2H),3.67(t,J=2.6Hz,1H),3.56(t,J=9.6Hz,2H),3.37(t,J=6.4Hz,2H),3.35( dd,9.6,2.6Hz,2H,2H),3.29(s,3H),3.11(t,J=9.6Hz,1H),1.62-1.53(m,4H),1.44-1.36(m,2H).

[0311] 2-O-(9-methoxynonyl)-myo-inositol (III_B-3): According to the general hydrolysis procedure F, 240 mg (III_B-3) was obtained from 430 mg (II_B-3) (yield 97%). HPLC-MS (condition B): rt = 2.53 min; m / z: 337 [M+1] + .

[0312] 2-O-(19-methoxynonadecayl)-myo-inositol (III_B-4): According to the general hydrolysis procedure C, 200 mg (III_B-4) was obtained from 337 mg (VIII_B-1) (yield 60%). HPLC-MS (condition B): rt = 4.43 min; m / z: 477 [M+1] + .

[0313] 2-O-(29-Methoxynonacousticyl)-myo-inositol (III_B-5): According to the general hydrolysis procedure C, 75 mg of (III_B-5) was obtained from 284 mg of (VIII_B-2) (yield 27%).

[0314] rac-4-O-(3-(p-tolyl)propyl)-myo-inositol (III_A-6): According to the general hydrolysis procedure S, 166.4 mg (III_A-6) was obtained from 344 mg (II_A-6) (yield 67%). HPLC-MS (condition A): rt = 2.87 min; m / z: 313 [M+1] + .

[0315] rac-4-O-(4-methylpentyl)-myo-inositol (III_A-7): According to the general hydrolysis procedure S, 225 mg (III_A-7) was obtained from 767 mg (II_A-7) (yield 43%). HPLC-MS (condition A): rt = 2.60 min; m / z: 265 [M+1] + .

[0316] rac-4-O-(6,6,6-trifluorohexyl)-myo-inositol (III_A-8): According to the general hydrolysis procedure S, 274 mg (III_A-8) was obtained from 424 mg (II_A-8) (yield 90%). HPLC-MS (condition A): rt = 2.66 min; m / z: 319 [M+1] + .

[0317] rac-4-O-(3-(4-methoxyphenyl)propyl)-myo-inositol (III_A-9): According to the general hydrolysis procedure S, 196 mg (III_A-9) was obtained from 409 mg (II_A-9) (yield 66%). HPLC-MS (condition A): rt = 2.66 min; m / z: 329 [M+1] + .

[0318] rac-4-O-(3-(3-(trifluoromethyl)phenyl)propyl)-myo-inositol (III_A-10): According to the general hydrolysis procedure S, 146 mg (III_A-10) was obtained from 209 mg (II_A-10) (yield 93%). HPLC-MS (condition A): rt = 3.01 min; m / z: 367 [M+1] + .

[0319] rac-4-O-(2-cyclopentylethyl)-myo-inositol (III_A-11): According to the general hydrolysis procedure S, 45 mg (III_A-11) was obtained from 68 mg (II_A-11) (yield 96%). HPLC-MS (condition A): rt = 2.65 min; m / z: 277 [M+1] + .

[0320] rac-4-O-(2-cyclopropylethyl)-myo-inositol (III_A-12): According to the general hydrolysis procedure S, 355 mg (III_A-12) was obtained from 486 mg (II_A-12) (yield 96%). HPLC-MS (condition A): rt = 1.09 min; m / z: 249 [M+1] + .

[0321] rac-4-O-(5-(1H-pyrazol-1-yl)pentyl)-myo-inositol (III_A-13): According to the general hydrolysis procedure S, 77 mg (III_A-13) was obtained from 137 mg (II_A-13) (yield 78%). HPLC-MS (condition A): rt = 1.65 min; m / z: 317 [M+1] + .

[0322] rac-4-O-(5-acetamidopentyl)-myo-inositol (III_A-14): According to the general hydrolysis procedure S, 180 mg (III_A-14) was obtained from 254 mg (II_A-14) (yield> 99%). HPLC-MS (condition A): rt = 2.71 min; m / z: 308 [M+1] + .

[0323] rac-4-O-(10-methoxycarbonyldecyl)-myo-inositol (III_A-15): According to the general hydrolysis procedure S, 30 mg (III_A-15) was obtained from 63 mg (II_A-15) (yield 64%). HPLC-MS (condition A): rt = 3.11 min; m / z: 379 [M+1] + .

[0324] rac-4-O-(10-(Benzyloxy)decyl)-myo-inositol (III_A-16): According to the general hydrolysis procedure S, 19 mg (III_A-16) was obtained from 25 mg (II_A-16) (yield 98%). HPLC-MS (condition A): rt = 3.54 min; m / z: 427 [M+1] + .

[0325] rac-4-O-methyl-myo-inositol (III_A-17): According to the general hydrolysis procedure S, 27 mg of (III_A-17) was obtained from 58 mg of (II_A-17) (yield 76%). 1 H NMR (400 MHz, CHLOROFORM-d) 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).

[0326] rac-4-O-(7-methoxyheptyl)-myo-inositol (III_A-18): According to the general hydrolysis procedure S, 103 mg (III_A-18) was obtained from 167 mg (II_A-18) (yield 87%). HPLC-MS (condition A): rt = 2.57 min; m / z: 309 [M+1] + .

[0327] rac-4-O-propyl-myo-inositol (III_A-19): According to the general hydrolysis procedure S, 66 mg of (III_A-19) was obtained from 128 mg of (II_A-19) (yield 80%). 1H NMR (400MHz, MeOH-d4) δ3.88(t,J=2.4Hz,1H),3.69(td,J=9.2,7.2Hz,1H),3.68(td,J=9.2,7.2Hz,1H),3.56(t,J= 9.5Hz,1H),3.39-3.33(m,2H),3.30-3.23(m,1H),3.19-3.12(m,1H),1.58(h,J=7.2Hz,2H),0.87(t,J=7.2Hz,3H).

[0328] rac-4-O-(3-(4-(2-(benzyloxycarbonyl)ethyl)-1H-1,2,3-triazol-1-yl)propyl)-myo-inositol (III_A-20): According to the general click reaction procedure M, 34 mg (III_A-20) (35%) was obtained from 57 mg (VI_A-1) and 61.3 mg (1.5 eq.) (20). In this case, flash chromatography was used. HPLC-MS (condition A): rt = 2.84 min; m / z: 452 [M+1] + .

[0329] rac-4-O-(6-(4-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl)hexyl)-myo-inositol (III_A-21): According to the general click reaction procedure M, 109 mg (III_A-21) (86%) was obtained from 99 mg (VI_A-2) and 27 mg (1 eq.) methyl propiolate. HPLC-MS (condition A): rt = 2.39 min; m / z: 390 [M+1] + .

[0330] 5-O-Propyl-myo-inositol (III_C-1): According to the general debenzylation procedure K, 15 mg of (III_C-1) was obtained from 107 mg of (II_C-1) (yield 42%). 1 H NMR(400MHz MeOH-d4)δ3.84(t,J=2.8,1H),3.64(t,J=7.4Hz,2H),3.56(t,J=9.6Hz,2H),3.24(dd, J=9.6, 2.8Hz, 2H), 2.86 (t, J=9.6Hz, 1H), 1.54 (q, J=7.4Hz, 3H), 0.83 (t, J=7.4Hz, 4H).

[0331] 5-O-(2-Cyclopropylethyl)-myo-inositol (III_C-2): According to the general debenzylation procedure K, 15 mg of (III_C-2) was obtained from 108 mg of (II_C-2) (yield 39%). 1H NMR (400MHz, MeOH-d4) δ3.88(t,J=2.8Hz,1H),3.80(t,J=7.2Hz,2H),3.61(t,J=9.6Hz,2H),3.29(dd,J=9.6,2. 8Hz, 3H), 2.91 (t, J = 9.6Hz, 1H), 1.47 (q, J = 7.2Hz, 2H), 0.80-0.62 (m, 1H), 0.41-0.30 (m, 2H), 0.07-0.10 (m, 2H).

[0332] 5-O-(9-Methoxynonyl)-myo-inositol (III_C-3): According to the general debenzylation procedure K, 27 mg of (III_C-3) was obtained from 127 mg of (II_C-3) (yield 50%). 1 H NMR(400MHz,MeOH-d4)δ3.96(t,J=2.8Hz,1H),3.80(t,J=7.0Hz,2H),3.67(d,J=9.6Hz,2H),3.40(t,J=6.8Hz,2H) ,3.35(dd,J=9.6,2.8Hz,2H),2.97(t,J=9.6Hz,1H),1.64(t,J=7.0Hz,3H),1.57(p,J=6.8Hz,3H),1.35(br,10H).

[0333] rac-1-O-propyl-myo-inositol (III_D-1): According to the general debenzylation procedure K, 46 mg of (III_C-1) was obtained from 107 mg of (IX_D-1) (yield 95%). 1 H NMR (400MHz, MeOH-d4) δ4.04(t,J=2.8Hz,1H),3.59(t,J=9.6Hz,1H),3.54(dt,J=9.2,7.2Hz,1H),3.53(t,J=9.6Hz,1H),3.38(dt,J=9.2, 7.2Hz, 1H), 3.24 (dd, J = 9.6, 2.8Hz, 1H), 3.09 (t, J = 9.6Hz, 1H), 3.01 (dd, J = 9.6, 2.8Hz, 1H), 1.55 (h, J = 7.2Hz, 2H), 0.85 (t, J = 7.2Hz, 3H).

[0334] rac-4-O-(6-amino-6-oxohexyl)-myo-inositol (III_A-22): According to the general hydrolysis procedure S, 50 mg of (III_A-19) was obtained from 72 mg of (II_A-21) (yield 80%). 1 H NMR (400 MHz, MeOH-d4 )δ3.94(t,J=2.5Hz,1H),3.82-3.77(m,2H),3.61(t,J=9.5Hz,1H),3.42-3.39(m,2H),3.34- 3.30(m,1H),3.23-3.19(m,1H),2.22(t,J=7.4Hz,2H),1.68-1.61(m,4H),1.47-1.39(m,2H).

[0335] 2-O-(5-(Benzyloxy)pentyl)-myo-inositol (III_B-7): According to the general hydrolysis procedure F, 75 mg (III_B-7) was obtained from 179 mg (II_B-5) (yield 71%). HPLC-MS (condition A): rt = 2.83 min; m / z: 357 [M+1] + ,379[M+23] + .

[0336] 2-O-(6,6,6-trifluorohexyl)-myo-inositol (III_B-8): According to the general debenzylation procedure K, 54 mg (III_B-8) was obtained from 85 mg (VIII_B'-1) (yield> 99%). HPLC-MS (condition A): rt = 2.69 min; m / z: 319 [M+1] + .

[0337] 2-O-(6-Amino-6-oxohexyl)-myo-inositol (III-B-9): According to the general debenzylation procedure K, 45 mg of (III_B-9) was obtained from 75 mg of (VIII_B'-2) (yield > 99%). 1 H NMR (400 MHz, MeOH-d 4 )δ3.78(t,J=6.4,1H),3.76(t,J=6.4,1H),3.69(q,J=3.0Hz,1H),3.59(td,J=10.0,3.0Hz,2H),3.39(dt,J= 10.0, 3.0Hz, 2H), 3.14 (td, J = 9.2, 3.6Hz, 1H), 2.20 (t, J = 7.6Hz, 2H), 1.67-1.57 (m, 4H), 1.47-1.39 (m, 2H).

[0338] 2-O-(2-cyclopentylethyl)-myo-inositol (III_B-10): According to the general debenzylation procedure K, 120 mg (III_B-10) was obtained from 200 mg (VIII_B'-3) (yield> 99%). HPLC-MS (condition A): rt = 2.69 min; m / z: 277 [M+1] +.

[0339] 2-O-(2-Cyclopropylethyl)-myo-inositol (III_B-11): According to the general debenzylation procedure K, 150 mg of (III_B-11) was obtained from 261 mg of (VIII_B'-4) (yield > 99%). 1 H NMR (400 MHz, MeOH-d 4 )δ3.84(t,J=6.9Hz,2H),3.70(t,J=2.7Hz,1H),3.58(t,J=9.5Hz,2H),3.37(dd,J=9.5,2.7Hz,2H),3 .12(t,J=9.2Hz,1H),1.50(q,J=6.9Hz,2H),0.81-0.69(m,1H),0.43-0.39(m,2H),0.07-0.03(m,2H).

[0340] 2-O-(5-Aminopentyl)-myo-inositol (III_B-12): According to the general hydrolysis procedure F, 50 mg of (III_B-12) was obtained from 105 mg of (II_B-6) (yield 93%). 1 H NMR (400 MHz, MeOH-d 4 )δ3.79(t,J=6.2Hz,2H),3.70(t,J=2.7Hz,1H),3.57(t,J=9.2Hz,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).

[0341] 2-O-Propargyl-myo-inositol (III_B-13): According to the general hydrolysis procedure F, 73 mg (III_B-13) was obtained from 183 mg (II_B-4) (yield 86%). 1 H NMR (400 MHz, MeOH-d 4 )δ4.49(d,J=2.6Hz,2H),3.93(t,J=2.8Hz,1H),3.57(t,J=9.6Hz,2H),3.40(dd,J=10.0,2.8Hz,2H),3.13(t,J=9.2Hz,1H),2.81(t,J=2.4Hz,1H).

[0342] 2-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (III_B-14): According to the general hydrolysis procedure F, 65 mg (III_B-14) was obtained from 142 mg (II_B-7) (yield 77%). HPLC-MS (condition A): rt = 1.28 min; m / z: 362 [M+1] + .

[0343] 2-O-(5-acetamidopentyl)-myo-inositol (III_B-15): According to the general amide formation procedure Q, 30 mg (III_B-15) (yield 56%) was obtained from 46 mg (II_B-12) and 30 mg (1 eq.) 2,5-dioxopyrrolidin-1-yl acetate. HPLC-MS (condition A): rt = 1.06 min; m / z: 308 [M+1] + .

[0344] 2-O-((1-(2-(methoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol (III_B-16): According to the general click reaction procedure L, 118 mg (III_B-16) (68%) was obtained from 109 mg (III_B-13) and 71 mg (1.1 eq.) (38). HPLC-MS (condition A): rt = 0.97 min; m / z: 348 [M+1] + .

[0345] 5-O-(5-Methoxypentyl)-myo-inositol (III_C-4): According to the general debenzylation procedure K, 17 mg of (III_C-4) was obtained from 46 mg of (II_C-4) (yield > 99%). 1 H NMR (400 MHz, MeOH-d 4 )δ3.94(t,J=2.8Hz,1H),3.79(t,J=6.7Hz,2H),3.66(t,J=9.5Hz,2H),3.40(t,J=6.5Hz,2H),3.36-3. 32(dd,J=10.0,2.8Hz,2H),3.32(s,3H),2.95(t,J=9.2Hz,1H),1.68-1.56(m,4H),1.47-1.40(m,2H).

[0346] 5-O-(6,6,6-Trifluorohexyl)-myo-inositol (III_C-5): According to the general debenzylation procedure K, 29 mg (III_C-5) was obtained from 160 mg (II_C-5) (yield 43%). 1H NMR (400 MHz, MeOH-d 4 )δ3.94(t,J=2.8Hz,1H),3.79(t,J=6.6Hz,2H),3.66(t,J=9.6Hz,2H),3.34(dd,J=10.0,2 .8Hz,2H),2.95(t,J=9.2Hz,1H),2.21-2.09(m,2H),1.68-1.56(m,4H),1.52-1.46(m,2H).

[0347] 5-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (III_C-6): According to the general debenzylation procedure K, 15 mg of (III_C-6) was obtained from 102 mg of (II_C-6) (yield 33%). 1 H NMR (400 MHz, MeOH-d 4 )δ7.97(s,1H),4.53(s,2H),4.42(t,J=7.1Hz,2H),3.94(t,J=2.8Hz,1H),3.78(t,J=6.6Hz,2H),3.65(t,J=9.5Hz,2H),3.37 (s, 3H), 3.33 (dd, J = 10.0.2.8Hz, 2H), 2.94 (t, J = 9.2Hz, 1H), 1.95 (p, J = 7.1Hz, 2H), 1.66 (p, J = 6.6Hz, 2H), 1.45-1.38 (m, 2H).

[0348] rac-1-O-(9-methoxynonyl)-myo-inositol (III_D-2): According to the general debenzylation procedure K, 109 mg (III_D-2) was obtained from 196 mg (IX_D-2) (yield> 99%). HPLC-MS (condition A): rt = 2.89 min; m / z: 337 [M+1] + .

[0349] rac-1-O-(2-cyclopropylethyl)-myo-inositol (III_D-3): According to the general debenzylation procedure K, 87 mg (III_D-3) was obtained from 181 mg (IX_D-3) (yield> 99%). HPLC-MS (condition A): rt = 1.06 min; m / z: 249 [M+1] + .

[0350] rac-1-O-(5-acetamidopentyl)-myo-inositol (III_D-4): According to the general debenzylation procedure K, 57 mg of (III_D-4) was obtained from 107 mg of (IX_D-4) (yield > 99%).1 H NMR (400 MHz, MeOH-d 4 )δ4.13(s,1H),3.70-3.60(m,3H),3.51(q,J=7.1Hz,1H),3.35-3.28(m,2H),3-20-3.16(m,3H) ,3.10(d,J=9.5Hz,1H),1.95(s,3H),1.69-1.60(m,2H),1.58-1.49(m,2H),1.47-1.39(m,2H).

[0351] rac-1-O-(6,6,6-trifluorohexyl)-myo-inositol (III_D-5): According to the general debenzylation procedure K, 55 mg (III_D-5) was obtained from 102 mg (IX_D-5) (yield> 99%). HPLC-MS (condition A): rt = 2.72 min; m / z: 319 [M+1] + ,341[M+23] + .

[0352] rac-1-O-(2-cyclopentylethyl)-myo-inositol (III_D-6): According to the general debenzylation procedure K, 76 mg (III_D-6) was obtained from 119 mg (IX_D-6) (yield 64%). HPLC-MS (condition A): rt = 2.72 min; m / z: 277 [M+1] + ,299[M+23] + .

[0353] rac-1-O-((l-(2-(methoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol (III_D-7): According to the general debenzylation procedure K, 130 mg (III_D-7) was obtained from 248 mg (IX_D-10) (yield 93%). HPLC-MS (condition A): rt = 0.99 min; m / z: 348 [M+1] + .

[0354] rac-1-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (III_D-8): According to the general debenzylation procedure K, 143 mg of (III_D-8) was obtained from 250 mg of (IX_D-8) (yield > 99%). 1 H NMR (400 MHz, MeOH-d 4)δ8.04(s,1H),4.57(s,2H),4.46(t,J=7.0Hz,2H),4.17(t,J=2.8Hz,1H), 3.74-3.65(m,3H),3.54(dt,J=9.4,6.5Hz,1H),3.41(s,3H),3.40-3.37(m 1H), 3.24 (t, J = 9.2Hz, 1H), 3.15 (dd, J = 10.0, 2.8Hz, 1H), 1.98 (p, J = 7.2Hz, 2H), 1.69 (p, J = 6.9Hz, 2H), 1.48-1.41 (m, 2H).

[0355] C.3. Intermediates IV_A, IV_B, IV_C and IV_D

[0356] rac-1,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-4-O-pentyl-myo-inositol (IV_A-1): According to the general phosphorylation procedure H, 57.6 mg (IV_A-1) was obtained from 76 mg (III_A-1) (yield 16%). HPLC-MS (condition A): rt = 4.15 min; m / z: 1161 [M+1] + .

[0357] rac-4-O-(5-(benzyloxy)pentyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-2): According to the general phosphorylation procedure H, 30 mg (IV_A-2) was obtained from 20 mg (III_A-2) (yield 42%). HPLC-MS (condition B): rt = 3.24 min; m / z: 1267 [M+1] + .

[0358] rac-4-O-(5-methoxypentyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-3): According to the general phosphorylation procedure H, 98 mg (IV_A-3) was obtained from 45 mg (III_A-3) (yield 51%). HPLC-MS (condition B): rt = 2.95 min; m / z: 1191 [M+1] + .

[0359] rac-4-O-(5-methoxycarbonylpentyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-4): According to the general phosphorylation procedure G, 23 mg (IV_A-4) was obtained from 42 mg (III_A-4) (yield 14%). HPLC-MS (condition B): rt = 2.99 min; m / z: 1219 [M+1] + .

[0360] rac-4-O-(2-(4-acetylpiperazin-1-yl)ethyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-5): According to the general phosphorylation procedure H, 29 mg (IV_A-5) was obtained from 24 mg (III_A-5) (yield 32%). HPLC-MS (condition B): rt = 2.37 min; m / z: 1245 [M+1] + .

[0361] 1,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-2-O-pentyl-myo-inositol (IV_B-1): According to the general phosphorylation procedure H, 399 mg (IV_B-1) was obtained from 150 mg (III_B-1) (yield 57%). HPLC-MS (condition A): rt = 4.15 min; m / z: 1161 [M+1] + .

[0362] 2-O-(5-methoxypentyl)-1,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-2): According to the general phosphorylation procedure H, 71 mg (IV_B-2) was obtained from 84 mg (III_B-2) (yield 19.9%). HPLC-MS (condition A): rt = 3.99 min; m / z: 1191.6 [M+1] + .

[0363] 2-O-(9-methoxynonyl)-1,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-3): According to the general phosphorylation procedure H, 110 mg (IV_B-3) was obtained from 240 mg (III_B-3) (yield 12.4%). HPLC-MS (condition B): rt = 3.95 min; m / z: 1247 [M+1] +,1264[M+23] + .

[0364] 2-O-(19-methoxynonadecayl)-1,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-4): According to the general phosphorylation procedure H, 80 mg (IV_B-4) was obtained from 200 mg (III_B-4) (yield 14%). HPLC-MS (condition B): rt = 5.17 min; m / z: 1387 [M+1] + .

[0365] 2-O-(29-Methoxynonacousticyl)-1,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-5): According to the general phosphorylation procedure H, 20 mg (IV_B-5) was obtained from 75 mg (III_B-5) (yield 11%). 31 P NMR (162 MHz, chloroform-d) δ -1.15, -4.17, -4.76.

[0366] Rac-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-4-O-(3-(p-tolyl)propyl)-myo-inositol (IV_A-6): According to the general phosphorylation procedure H, 44.6 mg (IV_A-6) was obtained from 50 mg (III_A-6) (yield 23%). 31 P 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] + .

[0367] rac-4-O-(4-methylpentyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-7): According to the general phosphorylation procedure H, 45 mg (IV_A-7) was obtained from 50 mg (III_A-7) (yield 20%). 31 PNMR (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] + .

[0368] Rac-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-4-O-(6,6,6-trifluorohexyl)-myo-inositol (IV_A-8): According to the general phosphorylation procedure H, 48 mg (IV_A-8) was obtained from 50 mg (III_A-8) (yield 25%). 31 PNMR (162 MHz, chloroform-d) δ -0.67, -1.28, -1.85, -2.99, -4.10. HPLC-MS (condition A): rt = 4.31 min; m / z: 1229 [M+1] + .

[0369] rac-4-O-(3-(4-methoxyphenyl)propyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-9): According to the general phosphorylation procedure H, 48 mg (IV_A-9) was obtained from 50 mg (III_A-9) (yield 25%). 31 P 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] + .

[0370] Rac-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-4-O-(3-(3-(trifluoromethyl)phenyl)propyl)-myo-inositol (IV_A-10): According to the general phosphorylation procedure H, 35 mg of (IV_A-10) was obtained from 50 mg of (III_A-10) (yield 20%). 31 P 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] + .

[0371] rac-4-O-(2-cyclopentylethyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-11): According to the general phosphorylation procedure H, 33 mg of (IV_A-11) was obtained from 45 mg of (III_A-11) (yield 17%). 31P NMR (162 MHz, chloroform-d) δ -0.59, -1.18, -1.93, -3.03, -4.15. HPLC-MS (condition A): rt = 4.46 min; m / z: 1187 [M+1] + .

[0372] Rac-4-O-(2-cyclopropylethyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-12): According to the general phosphorylation procedure H, 47 mg (IV_A-12) was obtained from 52 mg (III_A-12) (yield 19%). 31 P 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] + .

[0373] Rac-1,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-4-O-(5-(1H-pyrazol-l-yl)pentyl)-myo-inositol (IV_A-13): According to the general phosphorylation procedure H, 100 mg of (IV_A-13) was obtained from 50 mg of (III_A-13) (yield 54%). 31 P 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] + .

[0374] Rac-4-O-(5-acetamidopentyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-14): According to the general phosphorylation procedure H, 14 mg (IV_A-14) was obtained from 35 mg (III_A-14) (yield 10%). 31 P 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] + .

[0375] Rac-4-O-(10-methoxycarbonyldecyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-15): According to the general phosphorylation procedure H, 7.5 mg (IV_A-15) was obtained from 30 mg (III_A-15) (yield 7%). 31 P 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] + .

[0376] Rac-4-O-(10-(Benzyloxy)decyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-16): According to the general phosphorylation procedure H, 13 mg (IV_A-16) was obtained from 19 mg (III_A-16) (yield 22%). 31 P 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] + .

[0377] Rac-4-O-methyl-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-17): According to the general phosphorylation procedure H, 10 mg (IV_A-17) was obtained from 27 mg (III_A-17) (yield 6%). 31 P 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] + .

[0378] Rac-4-O-(7-methoxyheptyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-18): According to the general phosphorylation procedure H, 32 mg (IV_A-18) was obtained from 50 mg (III_A-18) (yield 16%). 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] + .

[0379] Rac-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-4-O-propyl-myo-inositol (IV_A-19): According to the general phosphorylation procedure H, 20 mg (IV_A-19) was obtained from 66 mg (III_A-19) (yield 6%). 31 P 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] + .

[0380] Rac-4-O-(3-(4-(2-(benzyloxycarbonyl)ethyl)-1H-1,2,3-triazol-1-yl)propyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-20): According to the general phosphorylation procedure H, 14 mg (IV_A-20) was obtained from 34 mg (III_A-20) (yield 14%). 31 P 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] + .

[0381] Rac-4-O-(6-(4-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl)hexyl)-1,2,3,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-21): According to the general phosphorylation procedure H, 15 mg of (IV_A-21) was obtained from 40 mg of (III_A-21) (yield 11%). 31 P 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] + .

[0382] l,2,3,4,6-Penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-5-O-propyl-myo-inositol (IV_C-1): According to the general phosphorylation procedure H, 10 mg of (IV_C-1) was obtained from 15 mg of (III_C-1) (yield 13%). 31 P 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] + .

[0383] 5-O-(2-Cyclopropylethyl)-l,2,3,4,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_C-2): According to the general phosphorylation procedure H, 10 mg of (IV_C-2) was obtained from 15 mg of (III_C-2) (yield 14%). 31 P 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] + .

[0384] 5-O-(9-Methoxynonyl)-1,2,3,4,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_C-3): According to the general phosphorylation procedure H, 15 mg (IV_C-3) was obtained from 27 mg (III_C-3) (yield 15%). 31 P 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] + .

[0385] Rac-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-1-O-propyl-myo-inositol (IV_D-1): According to the general phosphorylation procedure H, 53 mg (IV_D-1) was obtained from 61 mg (III_D-1) (yield 17%). 31 P 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] + .

[0386] Rac-4-O-(6-amino-6-oxohexyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_A-22): According to the general phosphorylation procedure H, 6 mg (IV_A-22) was obtained from 130 mg (III_A-22) (yield 1%). 31 P 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] + .

[0387] l,3,4,5,6-Penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-2-O-propargyl-myo-inositol (IV_B-6): According to the general phosphorylation procedure H, 10 mg (IV_B-6) was obtained from 54 mg (III_B-13) (yield 3.6%). 31 P 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] + .

[0388] 2-O-(5-(Benzyloxy)pentyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-7): According to the general phosphorylation procedure H, 75 mg (IV_B-7) was obtained from 67 mg (III_B-7) (yield 32%). 31 P 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] + .

[0389] 2-O-(6,6,6-trifluorohexyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-8): According to the general phosphorylation procedure R, 56 mg (IV_B-8) was obtained from 54 mg (III_B-8) (yield 27%). 31 P NMR (162 MHz, chloroform-d) δ -0.76, -3.76, -4.57. HPLC-MS (condition A): rt = 4.37 min; m / z: 1229 [M+1]+ .

[0390] 2-O-(6-Amino-6-oxohexyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-9): According to the general phosphorylation procedure R, 23 mg (IV_B-9) was obtained from 46 mg (III_B-9) (yield 14%). 31 P 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] + .

[0391] 2-O-(2-Cyclopentylethyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-10): According to the general phosphorylation procedure R, 124 mg (IV_B-10) was obtained from 121 mg (III_B-10) (yield 24%). 31 P 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] + .

[0392] 2-O-(2-Cyclopropylethyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-11): According to the general phosphorylation procedure H, 85 mg of (IV_B-11) was obtained from 62 mg of (III_B-11) (yield 29%). 31 P 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] + .

[0393] 2-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-1,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-12): According to the general phosphorylation procedure G, 25 mg (IV_B-12) was obtained from 65 mg (III_B-14) (yield 11%). 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] + .

[0394] 2-O-(5-Acetylaminopentyl)-l,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-13): According to the general phosphorylation procedure H, 10 mg (IV_B-13) was obtained from 30 mg (III_B-15) (yield 8%). 31 P 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] + .

[0395] 2-O-((l-(2-(Methoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-1,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_B-14): According to the general phosphorylation procedure G, 101 mg (IV_B-14) was obtained from 118 mg (III_B-16) (yield 24%). 31 P 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] + .

[0396] 5-O-(5-methoxypentyl)-l,2,3,4,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_C-4): According to the general phosphorylation procedure H, 6 mg (IV_C-4) was obtained from 23 mg (III_C-4) (yield 6%). 31 P 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] + .

[0397] 5-O-(6,6,6-trifluorohexyl)-l,2,3,4,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_C-5): According to the general phosphorylation procedure H, 10 mg (IV_C-5) was obtained from 28 mg (III_C-5) (yield 9%). 31 P 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] + .

[0398] 5-O-(5-(4-(Methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-1,2,3,4,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_C-6): According to the general phosphorylation procedure H, 7 mg (IV_C-6) was obtained from 15 mg (III_C-6) (yield 13%). 31 P 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] + .

[0399] Rac-1-O-(9-methoxynonyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-2): According to the general phosphorylation procedure H, 100 mg of (IV_D-2) was obtained from 113 mg of (III_D-2) (yield 24%). 31 PNMR (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] + .

[0400] rac-1-O-(2-cyclopropylethyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-3): According to the general phosphorylation procedure H, 90 mg (IV_D-3) was obtained from 96 mg (III_D-3) (yield 20%). 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] + .

[0401] Rac-1-O-(5-acetamidopentyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-4): According to the general phosphorylation procedure G, 10 mg (IV_D-4) was obtained from 59 mg (III_D-4) (yield 4%). 31 P 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] + .

[0402] Rac-1-O-(6,6,6-trifluorohexyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-5): According to the general phosphorylation procedure H, 25 mg (IV_D-5) was obtained from 64 mg (III_D-5) (yield 10%). 31 P 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] + .

[0403] Rac-1-O-(2-cyclopentylethyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-6): According to the general phosphorylation procedure H, 25 mg (IV_D-6) was obtained from 71 mg (III_D-6) (yield 8%). 31 P 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] + .

[0404] rac-1-O-((l-(2-(methoxycarbonyl)ethyl)-lH-1,2,3-triazol-4-yl)methyl)-2,3,4,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-7): According to the general phosphorylation procedure G, 104 mg (IV_D-7) was obtained from 130 mg (III_D-7) (yield 22%). 31 P 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] + .

[0405] Rac-1-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-2,3,4,5,6-penta-O-(3-oxido-1,5-dihydrobenzo[e][1,3,2]dioxaphosphin-3-yl)-myo-inositol (IV_D-8): According to the general phosphorylation procedure H, 10 mg (IV_D-8) was obtained from 46 mg (III_D-8) (yield 6%). 31 P 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] + .

[0406] C.4. Intermediates V_A, V_B, V_C and V_D

[0407] rac-4-O-(3-azidopropyl)-2-O-tert-butyldimethylsilyl-1,3,5-O-methy1-myo-inositol (V_A-1): According to the general alkylation procedure A, 85 mg (V_A-1) (19%) was obtained from 613 mg (2.1 eq.) (18). HPLC-MS (condition B): rt = 3.15 min; m / z: 388 [M+1] + .

[0408] rac-4-O-(6-azidohexyl)-2-O-tert-butyldimethylsilyl-1,3,5-O-methy1-myo-inositol (V_A-2): According to the general alkylation procedure A, 36 mg (V_A-2) (13%) was obtained from 391 mg (2 eq.) (22). HPLC-MS (condition B): rt = 4.83 min; m / z: 430 [M+1] + .

[0409] 2-O-(5-azidopentyl)-4,6-bis-O-(4-methoxybenzyl)-l,3,5-O-methylene-myo-inositol (V_B-1): According to the general alkylation procedure A, 225 mg (V_B-1) was obtained from 236 mg (3) and 311 mg (2 eq) (37) (yield 76%). HPLC-MS (condition A): rt = 4.55 min; m / z: 542 [M+1] + .

[0410] 5-O-(5-azidopentyl)-1,2,3,4,6-penta-O-benzyl-myo-inositol (V_C-1): According to the general alkylation procedure A, 218 mg (V_C-1) (yield 93%) was obtained from 200 mg (33) and 180 mg (2 eq) of (37). HPLC-MS (condition A): rt = 6.30 min; m / z: 765 [M+23] + .

[0411] rac-1-O-(5-azidopentyl)-2,4,6-tri-O-benzyl-3,5-O-ethylidene-myo-inositol (V_D-1): According to the general alkylation procedure B, 351 mg (V_D-1) was obtained from 285 mg (34) and 254 mg (1.5 eq) (37) (yield> 99%). HPLC-MS (condition A): rt = 5.55 min; m / z: 610 [M+23] + .

[0412] C.5. Intermediate VI_A

[0413] Rac-4-O-(3-azidopropyl)-myo-inositol (VI_A-1): According to the general hydrolysis procedure S, 110 mg (VI_A-1) (97%) was obtained from 166 mg (VI_A-1). HPLC-MS (condition A): rt = 2.59 min; m / z: 265 [M+1] + .

[0414] rac-4-O-(6-azidohexyl)-myo-inositol (VI_A-2): According to the general hydrolysis procedure S, 160 mg (VI_A-2) (81%) was obtained from 279 mg (VI_A-2). HPLC-MS (condition A): rt = 2.59 min; m / z: 306 [M+1] + .

[0415] C.6. Intermediate VII_A

[0416] Rac-4-O-(3-azidopropyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (VII_A-1): According to the general phosphorylation procedure H, 15 mg (VII_A-2) was obtained from 55 mg (VI_A-1) (yield 6%). 31 PNMR (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] + .

[0417] Rac-4-O-(3-azidopropyl)-l,2,3,5,6-penta-O-(3-oxido-l,5-dihydrobenzo[e][l,3,2]dioxaphosphin-3-yl)-myo-inositol (VII_A-2): According to the general phosphorylation procedure H, 44 mg (VII_A-2) was obtained from 40 mg (VI_A-1) (yield 28%). 31 P 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] + .

[0418] C.7. Intermediates VIII_B and VIII-B'

[0419] 2-O-(19-Methoxynonadecayl)-1,3,5-O-methy1-myo-inositol (VIII_B-1): According to the general debenzylation procedure K, 337 mg (VIII_B-1) was obtained from 504 mg (II_B'-1) (yield 91%). 1 H NMR (400MHz, chloroform-d) δ5.50(d,J=1.3Hz,1H),4.58(t,J=3.9Hz,2H),4.32(br,2H),4.27(br,1H),3.82(br,1H),3.62(t ,J=6.8Hz,2H),3.35(t,J=6.8Hz,2H),3.31(s,3H),1.67(p,J=7.2Hz,2H),1.54(p,J=7.2Hz,2H),1.38-1.18(s,50H).

[0420] 2-O-(29-Methoxynonacousticyl)-1,3,5-O-methy1-myo-inositol (VIII_B-2): According to the general debenzylation procedure K, 282 mg (VIII_B-2) was obtained from 776 mg (II_B'-2) (yield 46%). 1 H NMR (400MHz, chloroform-d) δ5.49(d,J=1.3Hz,1H),4.57(t,J=4.0Hz,2H),4.32(dt,J=4.7,1.7Hz,2H),4.26(br,1H),3.82(d,J=1.7Hz,1H) ,3.61(t,J=6.8Hz,2H),3.35(t,J=6.8Hz,2H),3.31(s,3H),1.65(q,J=8.7,7.0Hz,2H),1.54(p,J=6.8Hz,2H),1.38-1.18(s,59H).

[0421] 4,6-Di-O-benzyl-2-O-(6,6,6-trifluorohexyl)-myo-inositol (VIII_B'-1): According to the general hydrolysis procedure S, 85 mg (VIII_B'-1) was obtained from 90 mg (II_B'-3) (yield 96%). HPLC-MS (condition A): rt = 4.19 min; m / z: 521 [M+23] + .

[0422] 2-O-(6-amino-6-oxohexyl)-4,6-di-O-benzyl-myo-inositol (VIII_B'-2): According to the general hydrolysis procedure S, 68 mg (VIII_B'-2) was obtained from 70 mg (II_B'-4) (yield> 99%). HPLC-MS (condition A): rt = 3.19 min; m / z: 474 [M+1] + .

[0423] 4,6-Di-O-benzyl-2-O-(2-cyclopentylethyl)-myo-inositol (VIII_B'-3): According to the general hydrolysis procedure S, 180 mg (VIII_B'-3) was obtained from 185 mg (II_B'-5) (yield>99%). HPLC-MS (condition A): rt=4.43 min; m / z: 457 [M+1] + ,479[M+23] + .

[0424] 4,6-Di-O-benzyl-2-O-(2-cyclopropylethyl)-myo-inositol (VIII_B'-4): According to the general hydrolysis procedure S, 230 mg (VIII_B'-4) was obtained from 237 mg (II_B'-6) (yield> 99%). HPLC-MS (condition A): rt = 4.43 min; m / z: 451 [M+23] + .

[0425] C.8. Intermediate IX_D

[0426] Rac-2,4,6-Tri-O-benzyl-1-O-propyl-myo-inositol (IX_D-1): According to the general hydrolysis procedure S, 63 mg (IX_D-1) (98%) was obtained from 68 mg (II_D-1). HPLC-MS (condition A): rt = 4.36 min; m / z: 511 [M+23] + .

[0427] rac-2,4,6-tri-O-benzyl-1-O-(9-methoxynonyl)-myo-inositol (IX_D-2): According to the general hydrolysis procedure S, 198 mg (IX_D-2) (68%) was obtained from 306 mg (II_D-2). HPLC-MS (condition A): rt = 5.29 min; m / z: 607 [M+1] + ,629[M+23] + .

[0428] Rac-2,4,6-tri-O-benzyl-1O-(2-cyclopropylethyl)-myo-inositol (IX_D-3): According to the general hydrolysis procedure S, 181 mg (IX_D-3) (74%) was obtained from 255 mg (II_D-3). HPLC-MS (condition A): rt = 4.77 min; m / z: 519 [M+1] + .

[0429] rac-1-O-(5-aminopentyl)-2,4,6-tri-O-benzyl-myo-inositol (IX_D-4): According to the general azide reduction procedure P, 198 mg (IX_D-4) (79%) was obtained from 262 mg (X_D-1). HPLC-MS (condition A): rt = 3.16 min; m / z: 536 [M+1] + .

[0430] Rac-2,4,6-tri-O-benzyl-1O-(6,6,6-trifluorohexyl)-myo-inositol (IX_D-5): According to the general hydrolysis procedure S, 102 mg (IX_D-5) (>99%) was obtained from 107 mg (II_D-5). HPLC-MS (condition A): rt = 4.89 min; m / z: 589 [M+1] + .

[0431] Rac-2,4,6-tri-O-benzyl-1O-(2-cyclopentylethyl)-myo-inositol (IX_D-6): According to the general hydrolysis procedure S, 118 mg (IX_D-6) (>99%) was obtained from 124 mg (II_D-6). HPLC-MS (condition A): rt = 5.28 min; m / z: 548 [M+1] + .

[0432] rac-1-O-(5-acetamidopentyl)-2,4,6-tri-O-benzyl-myo-inositol (IX_D-7): According to the general amide formation procedure Q, 107 mg (IX_D-7) (89%) was obtained from 112 mg (IX_D-4) and 36 mg (1.1 eq.) 2,5-dioxopyrrolidin-1-yl acetate. HPLC-MS (condition A): rt = 3.82 min; m / z: 579 [M+1] + .

[0433] Rac-2,4,6-tri-O-benzyl-1O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol (IX_D-8): According to the general click reaction procedure M, 254 mg (IX_D-8) (>99%) was obtained from 226 mg (X_D-1) and 56 mg (2 eq.) 3-methoxyprop-1-yne. HPLC-MS (condition A): rt = 4.01 min; m / z: 633 [M+1] + .

[0434] rac-2,4,6-tri-O-benzyl-2-O-propargyl-myo-inositol (IX_D-9): According to the general hydrolysis procedure S, 120 mg (IX_D-9) (77%) was obtained from 164 mg (II_D-4). HPLC-MS (condition A): rt = 4.24 min; m / z: 489 [M+1] + .

[0435] Rac-2,4,6-tri-O-benzyl-1O-((1-(2-(methoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol (IX_D-10): According to the general click reaction procedure L, 234 mg (IX_D-10) (>99%) was obtained from 185 mg (IX_D-9) and 54 mg (1.1 eq.) (38). HPLC-MS (condition A): rt = 3.88 min; m / z: 618 [M+1] + .

[0436] C.9 Intermediate X_D

[0437] rac-1-O-(5-azidopentyl)-2,4,6-tri-O-benzyl-myo-inositol (X_D-1): According to the general hydrolysis procedure S, 263 mg (X_D-1) (70%) was obtained from 394 mg (V_D-1). HPLC-MS (condition A): rt = 4.74 min; m / z: 585 [M+23] + .

[0438] D. Characterization of Compounds: Analytical and Spectroscopic Testing

[0439] D.1.NMR

[0440] In the Agilent VNMRS-400 (at 400.10 MHz 1 H and at 162MHz 31 NMR spectra were recorded on 1 In H-NMR, chemical shifts are expressed in ppm relative to TMS, and coupling constants (J) are expressed in Hz. 31 In P NMR, phosphorus NMR spectra are collected without an internal standard. Usually phosphoric acid is used as the internal standard, but there is a concern that it may affect 1 H-NMR was therefore not used.

[0441] D.2.HPLC-MS

[0442] Condition A: High performance liquid chromatography (HPLC) 2795 Alliance Waters Aquity coupled with detector DAD Agilent1100 and detector MS Waters ESI triple cuadrupolo Quattro micro, 10 μL of MeOH containing sample was injected. Mass spectra (MS) were analyzed by FIA (flux injection analysis) coupled with LCT Premier orthogonal acceleration time-of-flight mass spectrometer, and data were acquired in positive mode by electrospray ionization (ESI). The spectrum was scanned between 50 and 1500 Da, values ​​were taken every 0.2 seconds, and peaks were shown in m / z (% of base peak). Stationary phase: ZORBAX Extend-C18 3.5 μm 2.1x 50 mm (T a 35℃).

[0443] Table 2: Condition A, mobile phase

[0444]

[0445] Table 3: Condition A, gradient

[0446]

[0447] Condition B: HPLC-MS was performed using a high performance liquid chromatograph 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 MeOH (c=0.5 mg / mL) containing the sample was injected. Data from the mass spectrometer were analyzed by electrospray ionization in positive and negative modes and peaks are shown as m / z (% of base peak). Stationary phase: ZORBAX Extend-C18 3.5 μm 2.1 x 50 mm (T a 35℃).

[0448] Table 4: Condition B, mobile phase

[0449] Mobile phase A Mobile phase B 1 Water + 0.05 formic acid Acetonitrile + 0.05 formic acid

[0450] Table 5: Condition B, gradient

[0451]

[0452] Condition C: HPLC-MS was performed using a high performance liquid chromatograph 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 MeOH (c=0.5 mg / mL) containing the sample was injected. Data from the mass spectrometer were analyzed in positive and negative modes by electrospray ionization and peaks are shown in m / z (% of base peak). Stationary phase: Xbridge BEH Amide 2.5 μm 4.6x150 mm XP.

[0453] Table 6: Condition C, mobile phase

[0454]

[0455]

[0456] Table 7: Condition C, gradient

[0457]

[0458] Condition D: HPLC-MS was performed using a high performance liquid chromatograph 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 MeOH (c=0.5 mg / mL) containing the sample was injected. Data from the mass spectrometer were analyzed by electrospray ionization in positive and negative modes and peaks are shown as m / z (% of base peak). Stationary phase: ZORBAX Extend-C18 3.5 μm 2.1 x 50 mm (T a 35℃).

[0459] Table 8: Condition D, mobile phase

[0460]

[0461] Table 9: Condition D, gradient

[0462]

[0463] Condition E: HPLC-MS was performed with a high performance liquid chromatograph 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 water containing sample (c=0.5 mg / mL) was injected. Data from the mass spectrometer were analyzed by electrospray ionization in positive and negative modes and peaks are shown as m / z (% of base peak). Stationary phase: Atlantis Premier BEHC18 AX 2.5 μm 2.1 x 100 mm, SN 1013130715504.

[0464] Table 10: Condition E, mobile phase

[0465]

[0466] Table 11: Condition E, gradient

[0467]

[0468] Condition F: HPLC-MS was performed with a high performance liquid chromatograph 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 water containing sample (c=0.5 mg / mL) was injected. Data from the mass spectrometer were analyzed by electrospray ionization in positive and negative modes and peaks are shown in m / z (% of base peak). Stationary phase: CORTECS T3 2.7 μm 2.1×150 mm, SN 1353131615509.

[0469] Table 12: Condition F, mobile phase

[0470]

[0471] Table 13: Condition F, gradient

[0472]

[0473] Example

[0474] Compound 1

[0475] rac-4-O-pentyl-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0476] According to the general phosphate deprotection procedure I, 14.9 mg of compound 1 (I_A-1) was obtained from 64 mg of (IV_A-1) (yield 31%). 1 H NMR (400 MHz, D 2 O)δ4.99-4.91(m,1H),4.42(q,J=9.6Hz,1H),4.15-3.95(m,3H),3.88-3.81(m,1H),3.7 9-3.71(m,2H),3.64(m,3H),1.65(p,7.2Hz,2H),1.35-1.29(m,4H),0.88(m,7.2Hz,3H). 31 P NMR (162MHz, D 2 O)δ3.94,3.26. HPLC-MS (condition C): rt=10.02min; m / z:797[M+1+DEA] + ,870[M+1+2DEA] + .

[0477] Compound 2

[0478] rac-4-O-(5-hydroxypentyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0479] According to the general phosphate deprotection procedure I, 8.24 mg of compound 2 (I_A-2) was obtained from 30 mg of (IV_A-2) (yield 39%). 1 H NMR (400 MHz, D 2 O)δ5.10-5.01(m,1H),4.50-4.39(m,1H),4.18-4.01(m,3H),3.92-3.85(m,1H),3.81-3.7 1(m,2H),3.61(t,J=6.8Hz,2H),1.70-1.63(m,2H),1.62-1.55(m,2H),1.45-1.38(m,2H). 31 P NMR (162MHz, D 2 O) 54.76, 2.86, 2.54, -0.16. HPLC-MS (condition C): rt = 10.36 min; m / z: 813 [M+1+DEA] + ,886[M+1+2DEA] + .

[0480] Compound 3

[0481] rac-4-O-(5-methoxypentyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0482] According to the general phosphate deprotection procedure I, 20.5 mg of compound 3 (I_A-3) was obtained from 97 mg of (IV_A-3) (yield 28%). 1 H NMR (400 MHz, D 2 O) 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] + .

[0483] Compound 4

[0484] rac-4-O-(5-carboxypentyl)-myo-inositol-1,2,3,5,6-penta(phosphate)undecanoate

[0485] According to the general phosphate deprotection procedure J, 4.4 mg of compound 4 (I_A-4) was obtained from 23 mg of (IV_A-4) (yield 25%). 1 H NMR (400 MHz, D 2 O)δ5.08(s,1H),5.51-4.43(m,1H),4.25-3.97(m,3H),3.86-3.72(m,4H),2.2 0(t,J=7.6Hz,2H),1.71-1.64(m,2H),1.562-1.55(m,2H),1.36-1-32(m,2H). HPLC-MS (condition C): rt=10.46min; m / z:841[M+1+DEA] + ,914[M+1+2DEA] + .

[0486] Compound 5

[0487] rac-4-O-(2-(4-acetylpiperazin-l-yl)ethyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0488] According to the general phosphate deprotection procedure I, 2.8 mg of compound 5 (I_A-5) was obtained from 31 mg of (IV_A-5) (yield 12%). 1 H NMR (400 MHz, D 2O)δ4.93-4.86(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=9.6Hz,2H),3.44-3.29(m,4H),2.18(s,3H). HPLC-MS (Condition C): rt=10.28min; m / z:808[M+1+DEA] + ,881[M+1+2DEA] + ,954[M+1+3DEA] + .

[0489] Compound 6

[0490] 2-O-pentyl-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0491] According to the general phosphate deprotection procedure I, 88.56 mg of compound 6 (I_B-1) was obtained from 325 mg of (IV_B-1) (yield 36%). 1 H NMR (400 MHz, D 2 O) δ4.36(m,3H),4.08(q,J=9.6Hz,1H),4.00(t,J=9.6Hz,2H),3.92(t,J=7.2Hz,2H),1.63(p,J=7.2Hz,2H),1.37-1.30(m,4H),0.96-0.80(m,3H). 31 PNMR(162MHz,D 2 O) 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] + .

[0492] Compound 7

[0493] 2-O-(5-methoxypentyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0494] According to the general phosphate deprotection procedure I, 6.7 mg of compound 7 (I_B-2) was obtained from 71 mg of (IV_B-2) (yield 12.5%). 1 H NMR (400 MHz, D 2O)δ4.38(q,J=9.5Hz,2H),4.20(br,1H),4.13-4-05(m,3H),3.90(t,J=7.2Hz,2H),3.51(t ,J=6.8Hz,2H),3.52(s,3H),1.67(p,J=7.2Hz,2H),1.62(p,J=7.2Hz,2H),1.40(p,J=7.2Hz 2H). 31 P NMR (162MHz, D 2 O)δ1.66(br),1.23(br). HPLC-MS (condition C): rt=10.24min; m / z:827[M+1+DEA] + ,900[M+1+2DEA] + .

[0495] Compound 8

[0496] 2-O-(9-methoxynonyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0497] According to the general phosphate deprotection procedure I, 10 mg of compound 8 (I_B-3) was obtained from 114 mg of (IV_B-3) (yield 11.4%). 1 H NMR (400 MHz, D 2 O) δ4.24(q,J=8.8Hz,2H),4.02(s,1H),3.95(t,J=9.7Hz,3H),3.71(t,J=6.8Hz,2H),3.33 (t,J=6.8Hz,2H),3.18(s,3H),1.48(t,J=6.8Hz,2H),1.42(q,J=6.8Hz,2H),1.17(m,10H). 31 P NMR (162MHz, D 2 O) 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] + .

[0498] Compound 9

[0499] 2-O-(19-methoxynonadecayl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0500] According to the general phosphate deprotection procedure I, 13.5 mg of compound 9 (I_B-4) was obtained from 35 mg of (IV_B-4) (yield 43%). 1 H NMR (400 MHz, D 2 O)δ4.20(q,J=8.8Hz,2H),4.08(s,1H),3.97-3.83(m,3H),3.73(t,J=7.5Hz ,2H),3.32(t,J=6.7Hz,2H),3.18(s,3H),1.50-1.39(m,4H),1.12(br,30H). 31 P NMR (162MHz, D 2 O) 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] + .

[0501] Compound 10

[0502] 2-O-(29-methoxynonacyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0503] According to the general phosphate deprotection procedure I, 5 mg of compound 10 (I_B-5) was obtained from 18 mg of (IV_B-5) (yield 34%). 1 H NMR (400 MHz, D 2 O) δ4.25(q,J=9.4Hz,2H),4.03-3.92(m,4H),3.72-3.66(m,2H),3.32(t,J=6.7Hz,2H),3.18(s,3H),1.51-1.38(m,4H),1.17-1.11(m,50H). 31 P NMR (162MHz, D 2 O)δ1.47,0.91,-0.25.

[0504] Compound 11

[0505] rac-4-O-(3-(p-tolyl)propyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0506] According to the general phosphate deprotection procedure I, 10 mg of compound 11 (I_A-6) was obtained from 44 mg of (IV_A-6) (yield 30%). 1 H NMR (400 MHz, D 2O) δ7.19(d,J=7.8Hz,2H),7.11(d,J=7.8Hz,2H),4.43-3.83(m,2H),3.81-3.66(m,2H),2.59(t,J=8Hz,2H),2.22(s,3H),1.90-1.78(m,2H). HPLC-MS (condition C): rt=9.90min; m / z:713[M+1] + ,785[M+1+DEA] + ,759[M+1+2DEA] + ,932[M+1+3DEA] + .

[0507] Compound 12

[0508] rac-4-O-(4-methylpentyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0509] According to the general phosphate deprotection procedure I, 10.2 mg of compound 12 (I_A-7) was obtained from 47 mg of (IV_A-7) (yield 30%). 1 H NMR (400 MHz, D 2 O)δ4.57-3.85(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=6.6Hz,6H). HPLC-MS (Condition E): rt=10.13min; m / z: 665[M+1] + ,738[M+1+DEA] + ,811[M+1+2DEA] + ,884[M+1+3DEA] + .

[0510] Compound 13

[0511] rac-4-O-(6,6,6-trifluorohexyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0512] According to the general phosphate deprotection procedure I, 3.8 mg of compound 13 (I_A-8) was obtained from 48 mg of (IV_A-8) (yield 10%). 1 H NMR (400 MHz, D 2O) δ4.58-3.86(m,6H),3.78-3.59(m,2H),2.17-2.05(m,2H),1.60(p,J=7.6Hz,2H),1.50(p,J=7.6Hz,2H),1.35(p,J=7.6Hz,2H). HPLC-MS (condition C): rt=10.49min; m / z:865[M+1+2DEA] + .

[0513] Compound 14

[0514] rac-4-O-(3-(4-methoxyphenyl)propyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0515] According to the general phosphate deprotection procedure I, 4.1 mg of compound 14 (I_A-9) was obtained from 48 mg of (IV_A-9) (yield 11%). 1 H NMR (400 MHz, D 2 O) δ7.23(d,J=8.6Hz,2H),6.88(d,J=8.6Hz,2H),4.46-3.80(m,6H),3.79-3.68(m,2H),2.58(t,J=8.0Hz,2H),1.85(p,J=8.0Hz,2H). HPLC-MS (condition C): rt=10.11min; m / z:729[M+1] + ,802[M+1+DEA] + ,875[M+1+2DEA] + .

[0516] Compound 15

[0517] rac-4-O-(3-(3-(trifluoromethyl)phenyl)propyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0518] According to the general phosphate deprotection procedure I, 8.6 mg of compound 15 (I_A-10) was obtained from 35 mg of (IV_A-10) (yield 32%). 1 H NMR (400 MHz, D 2O)δ7.59(s,1H),7.53(d,J=7.8Hz,1H),7.46(d,J=7.8Hz,1H),7.41(t,J=7.8Hz,1H ), 4.50-3.89 (m, 5H), 3.87-3.72 (m, 3H), 2.71 (t, J = 8.0Hz, 2H), 1.95-1.83 (m, 2H). HPLC-MS (condition C): rt=9.55min; m / z:767[M+1] + ,840[M+1+DEA] + ,913[M+1+2DEA] + .

[0519] Compound 16

[0520] rac-4-O-(2-cyclopentylethyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0521] According to the general phosphate deprotection procedure I, 6.6 mg of compound 16 (I_A-11) was obtained from 33 mg of (IV_A-11) (yield 26%). 1 H NMR (400 MHz, D 2 O)δ4.49-3.81(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),1.14-0.99(m,2H). HPLC-MS (condition C): rt=10.34min; m / z: 677[M+1] + ,823[M+1+2DEA] + .

[0522] Compound 17

[0523] rac-4-O-(2-cyclopropylethyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0524] According to the general phosphate deprotection procedure I, 9.5 mg of compound 17 (I_A-12) was obtained from 46 mg of (IV_A-12) (yield 27%). 1 H NMR (400 MHz, D 2O)δ4.55-3.84(m,6H),3.77-3.71(m,2H),1.44(q,J=7.3Hz,2H),0.74-0.59(m,1H),0.32-0.21(m,2H),0.10-0.10(m,2H). HPLC-MS (condition C): rt=10.77min; m / z: 649[M+1] + ,795[M+1+2DEA] + .

[0525] Compound 18

[0526] rac-4-O-(5-(1H-pyrazol-1-yl)pentyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0527] According to the general phosphate deprotection procedure I, 18.8 mg of compound 18 (I_A-13) was obtained from 100 mg of (IV_A-13) (yield 25%). 1 H NMR (400 MHz, D 2 O)δ7.60(dd,J=2.2,0.8Hz,1H),7.46(dd,J=2.2,0.8Hz,1H),6.24(t,J=2.2Hz,1H),4.63-3.89(m,6H),4 .08(t,J=7.2Hz,2H),3.73-3.56(m,2H),1.76(p,J=7.2Hz,2H),1.62-1.51(m,2H),1.18(p,J=7.2Hz,2H). HPLC-MS (condition C): rt=10.13min; m / z:717[M+1] + ,790[M+1+DEA] + ,863[M+1+2DEA] + .

[0528] Compound 19

[0529] rac-4-O-(5-acetylaminopentyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0530] According to the general phosphate deprotection procedure I, 3.1 mg of compound 19 (I_A-14) was obtained from 14 mg of (IV_A-14) (yield 29%). 1 H NMR (400 MHz, D 2O) δ4.55-3.84(m,6H),3.70-3.47(m,2H),3.09(t,J=6.8Hz,2H),1.90(s,3H),1.55-1.42(m,2H),1.25-1.18(m,4H). HPLC-MS (Condition E): rt=4.88min; m / z:781[M+1+DEA] + ,854[M+1+2DEA] + .

[0531] Compound 20

[0532] rac-4-O-(10-carboxydecyl)-myo-inositol-1,2,3,5,6-penta(phosphate)undecanoate

[0533] According to the general phosphate deprotection procedure J, 3.4 mg of compound 20 (I_A-15) was obtained from 7.5 mg of (IV_A-15) (yield 59%). 1 H NMR (400 MHz, D 2 O) δ4.58-3.76(m,6H),3.78-3.58(m,2H),2.08(t,J=7.6Hz,2H),1.61-1.52(m,2H),1.45(t,J=7.6Hz,2H),1.21(br,12H). HPLC-MS (Condition E): rt=5.20min; m / z:838[M+1+DEA] + ,911[M+1+2DEA] + ,984[M+1+3DEA] + .

[0534] Compound 21

[0535] rac-4-O-(10-hydroxydecyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0536] According to the general phosphate deprotection procedure I, 2.8 mg of compound 21 (I_A-16) was obtained from 12.9 mg of (IV_A-16) (yield 31%). 1 H NMR (400 MHz, D 2 O) δ4.49-3.74(m,6H),3.72-3.63(m,2H),3.51(t,J=6.8Hz,2H),1.60-1.53(m,2H),1.45(t,J=6.8Hz,2H),1.22(br,12H). HPLC-MS (condition F): rt=6.27min; m / z: 810[M+1+DEA] +,883[M+1+2DEA] + .

[0537] Compound 22

[0538] rac-4-O-methyl-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0539] According to the general phosphate deprotection procedure I, 0.6 mg of compound 22 (I_A-17) was obtained from 10 mg of (IV_A-17) (yield 8%). 1 H NMR (400 MHz, D 2 O)δ4.49-3.77(m,6H),3.52(s,3H). HPLC-MS (Condition E): rt=2.26min; m / z: 668[M+1+DEA] + ,741[M+1+2DEA] + ,814[M+1+3DEA] + .

[0540] Compound 23

[0541] rac-4-O-(7-methoxyheptyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0542] According to the general phosphate deprotection procedure I, 9.7 mg of compound 23 (I_A-18) was obtained from 30 mg of (IV_A-18) (yield 42%). 1 H NMR (400 MHz, D 2 O) δ4.45-3.79(m,5H),3.77-3.60(m,3H),3.40(t,J=6.8Hz,2H),3.26(s,3H),1.66-1.38(m,4H),1.25(br,6H). HPLC-MS (Condition C): rt=10.98min; m / z:855[M+1+2DEA] + .

[0543] Compound 24

[0544] rac-4-O-propyl-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0545] According to the general phosphate deprotection procedure I, 1.5 mg of compound 24 (I_A-19) was obtained from 20 mg of (IV_A-19) (yield 10%). 1 H NMR (400 MHz, D 2O) 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] + .

[0546] Compound 25

[0547] rac-4-O-(3-(4-(2-carboxyethyl)-1H-1,2,3-triazol-1-yl)propyl)-myo-inositol-1,2,3,5,6-penta(phosphate) undecanoate

[0548] According to the general phosphate deprotection procedure J, 3.0 mg of compound 25 (I_A-20) was obtained from 14 mg of (IV_A-20) (yield 29%). 1 H NMR (400 MHz, D 2 O)δ7.81(s,1H),4.53-4.44(m,2H),4.39-3.60(m,8H),2.84(t,J=8Hz,2H),2.44(t,J=8Hz,2H),2.16-2.05(m,2H). HPLC-MS (Condition E): rt=4.73min; m / z:762[M+1] + ,835[M+1+DEA] + ,908[M+1+2DEA] + ,981[M+1+3DEA] + .

[0549] Compound 26

[0550] rac-4-O-(6-(4-(carboxy)-1H-1,2,3-triazol-1-yl)hexyl)-myo-inositol-1,2,3,5,6-penta(phosphate) undecanoate

[0551] According to the general phosphate deprotection procedure J, 1.9 mg of compound 26 (I_A-21) was obtained from 15 mg of (IV_A-21) (yield 16%). 1 H NMR (400 MHz, D 2O) δ8.13 (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] + .

[0552] Compound 27

[0553] rac-4-O-(3-aminopropyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0554] According to the general phosphate deprotection procedure I, 1.9 mg of compound 27 (I_A-22) was obtained from 15 mg of (VI_A-1) (yield 17%). 1 H NMR (400 MHz, D 2 O) δ4.40-3.80 (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] + .

[0555] Compound 28

[0556] rac-4-O-(6-aminohexyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0557] According to the general phosphate deprotection procedure I, 15.6 mg of compound 28 (I_A-23) was obtained from 44 mg of (VI_A-2) (yield 48%). 1 H NMR (400 MHz, D 2 O) δ4.40-3.80(m,6H),3.55-3.65(m,2H),2.92(dd,J=7.6,5.6Hz,2H),1.70-1.40(m,4H),1.28-1.13(m,4H). HPLC-MS (condition C): rt=9.23min; m / z:752[M+1+DEA] + ,825[M+1+2DEA] + .

[0558] Compound 29

[0559] 5-O-propyl-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0560] According to the general phosphate deprotection procedure I, 3.3 mg of compound 29 (I_C-1) was obtained from 10 mg of (IV_C-1) (yield 45%). 1 H NMR (400 MHz, D 2 O) δ4.64-4.56(m,1H),4.38(q,J=9.6Hz,2H),4.02-3.93(m,2H),3.71(t,J=7. 4Hz, 2H), 3.34 (t, J = 9.6Hz, 1H), 1.58 (q, J = 7.4Hz, 2H), 0.81 (t, J = 7.4Hz, 3H). HPLC-MS (Condition E): rt=3.41min; m / z: 696[M+1+DEA] + ,769[M+1+2DEA] + ,842[M+1+3DEA] + .

[0561] Compound 30

[0562] 5-O-(2-cyclopropylethyl)-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0563] According to the general phosphate deprotection procedure I, 3.53 mg of compound 30 (I_C-2) was obtained from 10 mg of (IV_C-2) (yield 47%). 1 H NMR (400 MHz, D 2 O)δ4.36(q,J=9.6Hz,2H),3.99-3.91(m,2H),3.81(t,J=7.6Hz,2H),3.65-3.55(m,1H),3.36- 3.26(m,1H),1.47(q,J=7.6Hz,2H),0.70-0.61(m,1H),0.32-0.26(m,2H),0.01--0.04(m,2H). HPLC-MS (Condition E): rt=4.96min; m / z:722[M+1+DEA] + ,795[M+1+2DEA] + ,868[M+1+3DEA] + .

[0564] Compound 31

[0565] 5-O-(9-methoxynonyl)-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0566] According to the general phosphate deprotection procedure I, 6.7 mg of compound 31 (I_C-3) was obtained from 15 mg of (IV_C-3) (yield 58%). 1 H NMR (400 MHz, D 2 O)δ4.54-4.46(m,2H),4.44-4.15(m,3H),3.84(br,1H),3.66(t,J=7.6Hz,2H),3.40 (t,J=6.8Hz,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=5.95min; m / z:810[M+1+DEA] + ,883[M+1+2DEA] + ,956[M+1+3DEA] + .

[0567] Compound 32

[0568] Rac-1-O-propyl-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0569] According to the general phosphate deprotection procedure I, 13.28 mg of compound 32 (I_D-1) was obtained from 53 mg of (IV_D-1) (yield 34%). 1 H NMR (400 MHz, D 2 O) δ4.60-3.80(m,6H),3.70-3.52(m,2H),1.66-1.53(m,2H),0.81(t,J=7.6Hz,3H). HPLC-MS (Condition E): rt=3.65min; m / z: 696[M+1+DEA] + ,769[M+1+2DEA] + ,842[M+1+3DEA] + .

[0570] Compound 33

[0571] rac-4-O-(6-amino-6-oxohexyl)-myo-inositol-1,2,3,5,6-penta(phosphate) decasodium salt

[0572] According to the general phosphate deprotection procedure I, 1.42 mg of compound 33 (I_A-24) was obtained from 6 mg of (IV_A-22) (yield 31%). 1 H NMR (400 MHz, D 2O)δ4.36(q,J=9.2Hz,1H),4.06(q,J=9.2Hz,1H),4.00(d,J=8.0Hz,1H),3.94(t,J=9.2Hz,1H),3.78(q,J=8.0Hz,1H),3.72-3 .67(m,1H)3.67(t,J=6.8Hz,2H),2.21(t,J=6.8Hz,1H),1.58(p,J=6.8Hz,2H),1.55(p,J=6.8Hz,2H),1.32(p,J=6.8Hz,2H). HPLC-MS (Condition E): rt=2.25min; m / z: 694[M+1] + ,767[M+1+DEA] + ,840[M+1+2DEA] + .

[0573] Compound 34

[0574] 2-O-propyl-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0575] According to the general phosphate deprotection procedure I, 5 mg of compound 34 (I_B-6) was obtained from 30 mg of (IV_B-6) (yield 23%). 1 H NMR (400 MHz, D 2 O) δ4.80-4.70(m,1H)4.55-4.43(m,2H),4.24(brs,1H),4.22-4.13(m,2H),3.84(t,J=7.2Hz,2H),1.64(q,J=7.2Hz,2H),0.94(t,J=7.2Hz,3H). HPLC-MS (Condition E): rt=4.85min; m / z: 623[M+1] + ,796[M+1+DEA] + ,769[M+1+2DEA] + .

[0576] Compound 35

[0577] 2-O-(5-acetylaminopentyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0578] According to the general phosphate deprotection procedure I, 8 mg of compound 35 (I_B-7) was obtained from 12 mg of (IV_B-13) (yield 89%). 1 H NMR (400 MHz, D 2O)δ4.80-4.70(m,1H),4.48-4.31(m,2H),4.13-3.87(m,5H),3.86-3.74(m,1H),3.19(t, J=6.7Hz,2H),1.99(s,3H),1.72-1.61(m,2H),1.56(q,J=7.6Hz,2H),1.46-1.37(m,2H). HPLC-MS (Condition E): rt=4.97min; m / z:781[M+1+DEA] + ,854[M+1+2DEA] + .

[0579] Compound 36

[0580] 2-O-(6,6,6-trifluorohexyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0581] According to the general phosphate deprotection procedure I, 8.5 mg of compound 36 (I_B-8) was obtained from 58 mg of (IV_B-8) (yield 20%). 1 H NMR (400 MHz, D 2 O)4.80-4.70(m,1H),δ4.45-4.30(m,2H),4.15-3.86(m,4H),3.86-3.70(m,1H),2.3 2-2.08(m,2H),1.67(p,J=7.6Hz,2H),1.60(p,J=7.6Hz,2H),1.47(p,J=7.6Hz,2H). 31 P NMR (162MHz, D 2 O) 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] + .

[0582] Compound 37

[0583] 2-O-(6-amino-6-oxohexyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0584] According to the general phosphate deprotection procedure I, 4.2 mg of compound 37 (I_B-9) was obtained from 24 mg of (IV_B-9) (yield 24%). 1 H NMR (400 MHz, D 2O) δ4.73-4.83(m,1H),4.43-4.31(m,2H),4.15-3.99(m,3H),3.96(m,2H),2.31(t,J=7.6Hz,2H),1.66(p,J=7.4Hz,4H),1.48-1.42(m,2H). 31 P NMR (162MHz, D 2 O)δ2.96,1.94,1.39. HPLC-MS (condition E): rt=1.77min; m / z: 694[M+1] + ,767[M+1+DEA] + ,840[M+1+2DEA] + ,913[M+1+3DEA] + .

[0585] Compound 38

[0586] 2-O-(2-cyclopentylethyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0587] According to the general phosphate deprotection procedure I, 7.2 mg of compound 38 (I_B-10) was obtained from 124 mg of (IV_B-10) (yield 7.7%). 1 H NMR (400 MHz, D 2 O) 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] + .

[0588] Compound 39

[0589] 2-O-(2-cyclopropylethyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0590] According to the general phosphate deprotection procedure I, 3.0 mg of compound 39 (I_B-11) was obtained from 65 mg of (IV_B-11) (yield 4.7%). 1H NMR (400 MHz, D 2 O)δ5.00-4.78(m,1H),4.33-4.15(m,2H),4.05-3.83(m,4H),3.84-3.68(m,1H), 1.44(q,J=7.2Hz,2H),0.77-0.60(m,1H),0.38-0.25(m,2H),0.07--0.08(m,2H). HPLC-MS (Condition E): rt=1.94min; m / z: 649[M+1] + ,722[M+1+DEA] + ,795[M+1+2DEA] + ,868[M+1+3DEA] + .

[0591] Compound 40

[0592] 2-O-(5-Hydroxypentyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0593] According to the general phosphate deprotection procedure I, 13.6 mg of compound 40 (I_B-12) was obtained from 73 mg of (IV_B-7) (yield 27%). 1 H NMR (400 MHz, D 2 O)δ5.21-4.73(m,2H),4.60-4.17(m,2H),4.40(q,J=9.6Hz,1H),4.08(q,J=9.6Hz,1H),4.03-3.89(m,1H),3.89 -3.70(m,1H),3.63(t,J=6.5Hz,2H),1.75-1.59(m,4H),1.48-1.44(m,2H). HPLC-MS (Condition E): rt=4.85min; m / z: 667[M+1] + .

[0594] Compound 41

[0595] 2-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0596] According to the general phosphate deprotection procedure I, 10.8 mg of compound 41 (I_B-13) was obtained from 25 mg of (IV_B-12) (yield 56%). 1 H NMR (400 MHz, D 2O)δ8.08(s,1H),4.61(s,2H),4.47(t,J=7.2Hz,2H),4.47-4.28(m,3H),4.17-3.87( m, 4H), 3.39 (s, 3H), 1.97 (p, J = 7.7Hz, 2H), 1.69 (p, J = 7.7Hz, 2H), 1.45-1.33 (m, 2H). 31 P NMR (162MHz, D 2 O) δ 3.65, 2.66, 1.67. HPLC-MS (condition E): rt = 5.33 min; m / z: 907 [M+1+2DEA] + .

[0597] Compound 42

[0598] 2-O-((1-(2-carboxyethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol-1,3,4,5,6-penta(phosphate)undecanoate

[0599] According to the general phosphate deprotection procedure J, 45 mg of compound 42 (I_B-14) was obtained from 100 mg of (IV_B-14) (yield 57%). 1 H NMR (400 MHz, D 2 O) δ8.16 (s, 1H), 5.07 (s, 2H), δ 4.73-4.83 (m, 1H), 4.63 (t, J = 7.2Hz, 3H), 4.32 (brs, 3H), 4.04 (brs, 2H), 2.81 (t, J = 7.2Hz, 2H). HPLC-MS (Condition E): rt=1.16min; m / z:880[M+1+2DEA] + ,953[M+1+3DEA] + .

[0600] Compound 43

[0601] 2-O-propargyl-myo-inositol-1,3,4,5,6-penta(phosphate) decasodium salt

[0602] According to the general phosphate deprotection procedure T, 7.5 mg of compound 43 (I_B-15) was obtained from 25 mg of (IV_B-6) (yield 40%). 1 H NMR (400 MHz, D 2 O) δ4.64 (s, 2H), 4.42-4.34 (m, 3H), 4.14-4.06 (m, 3H), 2.88 (t, J = 2.4Hz, 1H). 31 PNMR(162MHz,D 2O) 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] + .

[0603] Compound 44

[0604] 5-O-(9-methoxypentyl)-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0605] According to the general phosphate deprotection procedure I, 1.7 mg of compound 44 (I_C-4) was obtained from 6 mg of (IV_C-4) (yield 37%). 1 H NMR (400 MHz, D 2 O)δ4.64-4.45(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=6.8Hz,2H),3.26(s,3H),1.65-1.56(m,2H),1.53(iq,J=6.8Hz,2H),1.20-1.23(m,2H). 31 PNMR(162MHz,D 2 O) 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] + .

[0606] Compound 45

[0607] 5-O-(6,6,6-trifluorohexyl)-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0608] According to the general phosphate deprotection procedure I, 1 mg of compound 45 (I_C-5) was obtained from 10 mg of (IV_C-5) (yield 13%). 1 H NMR (400 MHz, D 2O)δ4.58-4.16(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=7.4Hz,2H),1.38-1.30(m,2H). HPLC-MS (Condition E): rt=6.12min; m / z:865[M+1+2DEA] + ,938[M+1+3DEA] + .

[0609] Compound 46

[0610] 5-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-1,2,3,4,6-penta(phosphate) decasodium salt

[0611] According to the general phosphate deprotection procedure I, 2.5 mg of compound 45 (I_C-6) was obtained from 7 mg of (IV_C-6) (yield 46%). 1 H NMR (400 MHz, D 2 O)δ7.99(s,1H),4.53(s,2H),4.50-4.35(m,1H),4.37(t,J=7.0Hz,2H),4.06-3.84(m,3H),3 .78-3.68(m,2H),3.30(s,3H),1.86(t,J=7.6Hz,2H),1.69-1.58(m,2H),1.33-1.14(m,4H). HPLC-MS (Condition E): rt=3.20min; m / z:762[M+1] + .

[0612] Compound 47

[0613] rac-1-O-(9-methoxynonyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0614] According to the general phosphate deprotection procedure I, 44 mg of compound 47 (I_D-2) was obtained from 100 mg of (IV_D-2) (yield 57%). 1 H NMR (400 MHz, D 2O)δ4.65-4.39(m,4H),4.29(d,J=11.6Hz,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=5.45min; m / z:810[M+1+DEA] + ,883[M+1+2DEA] + .

[0615] Compound 48

[0616] rac-1-O-(2-cyclopropylethyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0617] According to the general phosphate deprotection procedure I, 15.4 mg of compound 48 (I_D-3) was obtained from 90 mg of (IV_D-3) (yield 23%). 1 H NMR (400 MHz, D 2 O)δ4.64-4.32(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=4.92min; m / z:722[M+1+DEA] + ,795[M+1+2DEA] + ,868[M+1+3DEA] + .

[0618] Compound 49

[0619] rac-1-O-(5-acetylaminopentyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0620] According to the general phosphate deprotection procedure I, 1.7 mg of compound 49 (I_D-4) was obtained from 10 mg of (IV_D-4) (yield 22%). 1 H NMR (400 MHz, D 2O)δ4.39-4.22(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,1 H), 3.09 (t, J = 6.5Hz, 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=3.10min; m / z:781[M+1+DEA] + ,854[M+1+2DEA] + ,926[M+1+3DEA] + .

[0621] Compound 50

[0622] rac-1-O-(6,6,6-trifluorohexyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt (CSC-san17-016)

[0623] According to the general phosphate deprotection procedure I, 0.6 mg of compound 50 (I_D-5) was obtained from 23 mg (IV_D-5) (yield 3.4%). HPLC-MS (condition E): rt = 6.83 min; m / z: 719 [M+1] + ,865[M+1+2DEA] + .

[0624] Compound 51

[0625] rac-1-O-(2-cyclopentylethyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0626] According to the general phosphate deprotection procedure I, 1.6 mg of compound 51 (I_D-6) (yield 8.5%) was obtained from 25 mg (IV_D-6). 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] + .

[0627] Compound 52

[0628] rac-1-O-(5-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)pentyl)-myo-inositol-2,3,4,5,6-penta(phosphate) decasodium salt

[0629] According to the general phosphate deprotection procedure I, 6.3 mg of compound 52 (I_D-7) was obtained from 10 mg of (IV_D-8) (yield 82%). 1 H NMR (400 MHz, D 2 O) δ8.07 (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] + .

[0630] Compound 53

[0631] rac-1-O-((1-(2-(methoxycarbonyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-myo-inositol-2,3,4,5,6-penta(phosphate)undecanoate

[0632] According to the general phosphate deprotection procedure J, 44.1 mg of compound 53 (I_D-8) was obtained from 104 mg (IV_D-7) (yield 55%). 1 H NMR (400 MHz, D 2 O) δ8.01 (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] + .

[0633] Pharmacological assays

[0634] A. In vitro inhibition of calcium phosphate crystallization

[0635] The in vitro potency of IP5-substituted compounds of the present invention (e.g., compounds 1 to 32) in inhibiting calcium phosphate crystallization in human plasma samples was evaluated according to a spectrophotometric assay previously described in the art (Ferrer M et al., Sci Rep 2017; 7:6858, doi: 10.1038 / s41598-017-07203-x).

[0636] 96-well plates were used. Derivatives were added to plasma at increasing concentrations in the range of 0-100 μM (1 volume of IP5-substituted compound of the present invention was added to every 19 volumes of plasma). Then, at room temperature, the plasma was centrifuged at 10,000 g and subsequently mixed with a mixture of 5 mM hydrogen phosphate and 41.67 mM calcium to reach a final concentration of 1.5 mM phosphate and 12.5 mM calcium, respectively. All reagent solutions were filtered and the pH was adjusted to 7.4.

[0637] Calcium phosphate crystallization was monitored spectrophotometrically for 30 min at room temperature by measuring the increase in absorbance at 550 nm using a Biotek Powerwave XS microplate spectrophotometer (BioTek Instruments, Inc., Winooski, VT, US). The plate was incubated on an orbital shaker at room temperature and the absorbance was measured every 3 min.

[0638] Plasma crystallization was assessed based on the slope measurement in the linear range between 6 and 24 min of the curve from absorbance increase relative to the logarithm of time. Use the slope obtained between 6 and 24 min to assess the effectiveness of different myo-inositol phosphate derivatives in preventing the formation of calcium phosphate crystals in vitro in human plasma samples. Crystallization inhibition was measured by comparing control samples (blank plasma) with the slope of samples containing inhibitors as shown below:

[0639]

[0640] See Table 14.

[0641] Table 14

[0642]

[0643]

[0644] legend:

[0645] +++-EC 50 ≤5μM

[0646] ++-5μM <EC 50 ≤10μM

[0647] +-EC 50>10μM

[0648] ***

[0649] It should be understood that the "Detailed Description" section, rather than 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 inventors, and thus, are not intended to limit the present invention and the appended claims in any way.

[0650] The present invention has been described above with the aid of functional building blocks that illustrate implementation of specified functions and relationships thereof. For ease of description, the boundaries of these functional building blocks have been arbitrarily defined herein. Alternative boundaries may be defined so long as the specified functions and relationships thereof are appropriately performed.

[0651] The foregoing description of specific embodiments will reveal the general nature of the invention so fully that others can easily modify and / or adapt to various applications such as specific embodiments by applying the knowledge of those skilled in the art without departing from the general concept of the invention, without undue experimentation. Therefore, based on the teachings and guidance set forth herein, such adaptations and modifications are intended to be within the meaning and range of equivalents of the disclosed embodiments. It should be understood that the wording or terminology herein is for the purpose of description rather than limitation, and thus the terms or wording of this specification will be interpreted by the skilled person based on the teachings and guidance.

[0652] The breadth and scope of the present invention should not be limited by any of the above-described embodiments, but should be defined only in accordance with the following claims and their equivalents.

Claims

1. A compound of 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 of formula II or formula III, or R1, R2, R3, R4 and R5 independently represent -OPO3H2, and R6 is a substituent of formula II or formula III, (ii) R1, R3, R4, R5 and R6 independently represent -OPO3H2, and R2 is a substituent of formula II or III, (iii) R1, R2, R3, R4 and R6 independently represent -OPO3H2, and R5 is a substituent of formula II or III, (iv) R2, R3, R4, R5 and R6 independently represent -OPO3H2, and R1 is a substituent of formula II; or R1, R2, R4, R5 and R6 independently represent -OPO3H2, and R3 is a substituent 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, -NHS02R, -NHCONRR', halogen, -CF3, alkyl, alkenyl, alkynyl, carbocycle, and heterocycle, and wherein R and R' are H or alkyl groups, and wherein, for Formula III, y and y' are integers 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, -NHS02R, -NHCONRR', halogen, and -CF3, and wherein R and R' are H or alkyl groups.

2. The compound according to claim 1, wherein the pharmaceutically acceptable salt is a sodium salt or a magnesium salt.

3. The compound of claim 3, wherein the sodium salt is a tetrasodium salt, a pentasodium salt, a hexasodium salt, a heptasodium salt, an octasodium salt, a nonasodium salt, a decasodium salt or an undecasodium salt.

4. The compound according to any one of claims 1 to 3, wherein the compound is selected from Compound 1 to Compound 53 and any combination thereof.

5. The compound according to claim 4, wherein the compound is Compound 1 having the following chemical structure:

6. The compound according to claim 4, wherein the compound is Compound 2 having the following chemical structure:

7. The compound according to claim 3, wherein the compound is compound 16 having the following chemical structure:

8. A pharmaceutical composition comprising a compound according to any one of claims 1 to 7 and at least one pharmaceutically acceptable excipient.

9. A method of inhibiting calcium salt / crystal formation or growth in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula I according to any one of claims 1 to 7, or a pharmaceutical composition according to claim 8.

10. The method of inhibiting the formation or growth of calcium salts / crystals according to claim 9, wherein the calcium salts / crystals are calcium phosphate.

11. The method of inhibiting calcium salt / crystal formation or growth according to claim 10, wherein the calcium phosphate is hydroxyapatite.

12. A method of treating or preventing a disease or condition associated with pathological crystallization in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula I according to any one of claims 1 to 7, or a pharmaceutical composition according to claim 8.

13. A method of inhibiting the progression of a crystallization process in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula I according to any one of claims 1 to 7, or a pharmaceutical composition according to claim 8.

14. The method according to any one of claims 9 to 13, wherein the subject is a human.

15. The method according to any one of claims 9 to 14, wherein the administration is topical, enteral or parenteral.

16. The method of claim 15, wherein the parenteral administration is intravenous or subcutaneous administration.

17. A compound selected from the group consisting of compounds listed in Table 1.

18. A kit or article of manufacture comprising at least one compound according to any one of claims 1 to 7, a pharmaceutical composition according to claim 8 or a compound according to claim 17.

19. A process for preparing a compound of formula I according to any one of claims 1 to 7, comprising using at least one compound according to claim 17.

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