Inositol derivatives for increasing chloride secretion and inhibiting inflammation

A compound of the formula:

• 17
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof, with the proviso that the compound of formula (II) is not D-3,6-Di-O-butyryl-myo-inositol 1,2,4,5-tetrakisphosphate octakis(acetoxymethyl) ester;
• or D-1,4-Di-O-butyryl-myo-inositol 2,3,5,6-tetrakisphosphate octakis(acetoxymethyl)ester;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A compound of the formula:

• 18
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• or each R1 may be taken together to form a cyclic structure;
• each R2 is independently selected from a group consisting of hydrogen and —C(R4)(R4)OC(O)C1-C4 straight or branched chain alkyl and each R3 is independently selected from a group consisting of —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —C1-C11—X—Y, where each X is independently selected from a group consisting of —O—, —S—, —Se—, —CO(O)—, —CS(O)—, —CO(S)—, —OC(O)—, —SC(O)—, OC(S)—, or —NH—, and where Y is independently selected from a group consisting of —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A compound of the formula:

• 19
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain allyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R4 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R4, except hydrogen, being unsubstituted or substituted with one or more halogen OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof;
• and
• each W is independently selected from a group consisting of —C(X)(Y)—, —C(X)(Y)—C(X)(Y)—, and —C(X)(Y)—C(X)(Y)—C(X)(Y)—;
• where
• X and Y are independently selected from a group consisting of hydrogen, —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof and hydrogen, —OH, —Oalkyl, —SH, —Salkyl, —CO(O)alkyl, —CS(O)alkyl, —CO(S)alkyl, —OC(O)alkyl, —SC(O)alkyl, —OC(S)alkyl, or —CONH2, or —CONHalkyl, or —CON(alkyl)(alkyl), —NH2;
• and
• n is an integer from 2 to 13, preferably 2 to 5;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A compound of the formula:

• 20
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, —NO2, —OC1-C6 alkyl, and —OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof;
• and
• each V is independently selected from a group consisting of —C(X)(Y)—, —C(X)(Y)—C(X)(Y)—, or —C(X)(Y)—C(X)(Y)—C(X)(Y)—;
• and
• m is an integer from 2 to 15, preferably from 2 to 5;
• and
• each W is independently selected from a group consisting of —C(X)—, —C(X)—C(X)(Y)—, or —C(X)—C(X)(Y)—C(X)(Y)—;
• and
• n is an integer from 1 to 15, preferably from 1 to 3;
• and
• X and Y are independently selected from a group consisting of hydrogen, —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof and hydrogen, —OH, —Oalkyl, —SH, —Salkyl, —CO(O)alkyl, —CS(O)alkyl, —CO(S)alkyl, —OC(O)alkyl, —SC(O)alkyl, —OC(S)alkyl, or —CONH2, or —CONHalkyl, or —CON(alkyl)(alkyl), —NH2;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method for regulating chloride secretion and/or inhibiting inflammation in a cell or tissue, comprising contacting the cell or tissue with an effective amount of a compound of formula (I):

• 21
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight- or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method of regulating chloride secretion and/or inhibiting inflammation in a human or animal patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of the formula:

• 22
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method for regulating chloride secretion and/or inhibiting inflammation in a cell or tissue, comprising contacting the cell or tissue with an effective amount of a compound of formula (II):

• 23
• each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, —NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method of regulating chloride secretion and/or inhibiting inflammation in a human or animal patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of the formula:

• 24
• each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain allyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, and —OC2-C20 straight or branched chain alkenyl or alkynyl;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, —NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method for regulating chloride secretion and/or inhibiting inflammation in a cell or tissue, comprising contacting the cell or tissue with an effective amount of a compound of formula (III):

• 25
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain al. V, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• or each R1 may be taken together to form a cyclic structure;
• each R2 is independently selected from a group consisting of hydrogen and —C(R4)(R4)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —C1-C11—X—Y, where each X is independently selected from a group consisting of —O—, —S—, —Se—, —CO(O)—, —CS(O)—, —CO(S)—, —OC(O)—, —SC(O)—, OC(S)—, or —NH—, and where Y is independently selected from a group consisting of —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof.
• each R4 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R4 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R4, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 al, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method of regulating chloride secretion and/or inhibiting inflammation in a human or animal patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of the formula (III):

• 26
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• or each R1 may be taken together to form a cyclic structure;
• each R2 is independently selected from a group consisting of hydrogen and —C(R4)(R4)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —C1-C11—X—Y, where each X is independently selected from a group consisting of —O—, —S—, —Se—, —CO(O)—, —CS(O)—, —CO(S)—, —OC(O)—, —SC(O)—, OC(S)—, or —NH—, and where Y is independently selected from a group consisting of —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof
• each R4 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R4 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R4, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method for regulating chloride secretion and/or inhibiting inflammation in a cell or tissue, comprising contacting the cell or tissue with an effective amount of a compound of formula (IV):

• 27
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20′ straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof;
• and
• each W is independently selected from a group consisting of —C(X)(Y)—, —C(X)(Y)—C(X)(Y)—, and —C(X)(Y)—C(X)(Y)—C(X)(Y)—;
• where
• X and Y are independently selected from a group consisting of hydrogen, —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof and hydrogen, —OH, —Oalkyl, —SH, —Salkyl, —CO(O)alkyl, —CS(O)alkyl, —CO(S)alkyl, —OC(O)alkyl, —SC(O)alkyl, —OC(S)alkyl, or —CONH2, or —CONHalkyl, or —CON(alkyl)(alkyl), —NH2;
• and
• n is an integer from 2 to 13, preferably 2 to 5;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method of regulating chloride secretion and/or inhibiting inflammation in a human or animal patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of the formula (T):

• 28
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, OH, C1-C6 alkyl, NO2, —OC1-C6 alkyl, and OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof;
• and
• each W is independently selected from a group consisting of —C(X)(Y)—, —C(X)(Y)—C(X)(Y)—, and —C(X)(Y)—C(X)(Y)—C(X)(Y)—;
• where
• X and Y are independently selected from a group consisting of hydrogen, —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof and hydrogen, —OH, —Oalkyl, —SH, —S allyl, —CO(O)alkyl, —CS(O)alkyl, —CO(S)alkyl, —OC(O)alkyl, —SC(O)alkyl, —OC(S)alkyl, or —CONH2, or —CONHalkyl, or —CON(alkyl)(alkyl), —NH2;
• and
• n is an integer from 2 to 13, preferably 2 to 5;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.

A method for regulating chloride secretion and/or inhibiting inflammation in a cell or tissue, comprising contacting the cell or tissue with an effective amount of a compound of formula (V):

• 29
• wherein each R1 is independently selected from the group consisting of hydrogen, —OH, —C1-C20 straight or branched chain alkyl, —C2-C20 straight or branched chain alkenyl or alkynyl, —OC(O)C1-C20 straight or branched chain alkyl and —OC1-C20 straight or branched chain alkyl, —OC2-C20 straight or branched chain alkenyl or alkynyl, and —OPO(OR2)2;
• each R2 is independently selected from a group consisting of hydrogen and —C(R3)(R3)OC(O)C1-C4 straight or branched chain alkyl;
• and
• each R3 is independently selected from a group consisting of hydrogen and —C1-C12 alkyl, both R3 taken as a 5- or 6-membered ring, phenyl, and benzyl, said R3, except hydrogen, being unsubstituted or substituted with one or more halogen, —OH, C1-C6 alkyl, —NO2, —OC1-C6 allyl, and —OC(O)C1-C6 alkyl groups, including racemates and diastereomers thereof;
• and
• each V is independently selected from a group consisting of —C(X)(Y)—, —C(X)(Y)—C(X)(Y)—, or —C(X)(Y)—C(X)(Y)—C(X)(Y)—;
• and
• m is an integer from 2 to 15, preferably from 2 to 5;
• and
• each W is independently selected from a group consisting of —C(X)—, —C(X)—C(X)(Y)—, or —C(X)—C(X)(Y)—C(X)(Y)—;
• and
• n is an integer from 1 to 15, preferably from 1 to 3;
• and
• X and Y are independently selected from a group consisting of hydrogen, —C1-C11 straight or branched chain alkyl, —C2-C12 straight or branched chain alkenyl or alkynyl, or unsubstituted and substituted benzyl, and phenyl, including racemates and diastereomers thereof and hydrogen, —OH, —Oalkyl, —SH, —Salkyl, —CO(O)alkyl, —CS(O)alkyl, —CO(S)alkyl, —OC(O)alkyl, —SC(O)alkyl, —OC(S)alkyl, or —CONH2, or —CONHalkyl;
• or —CON(alkyl)(alkyl), —NH2;
• and the racemates, diastereomers and pharmaceutically acceptable salts thereof.