Use Of Methanol And Prodrugs Thereof In Therapy

A compound of the following structural formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• each X is independently —C(O)—, —Y—C(O)—, —C(O)—Y—C(O)—, —Y—CH2—, —C(O)—Y—CH2— or a covalent bond;
• each Y is independently O or N(R1);
• each R1 is independently —H, formyl, —CO2H, —CO2R2, —CH2—OR2, —CO2(C2-C5)alkyl or —CO2CH2—(C6-C15)aryl;
• or
• R is —H, -D, —O*CH3, —O*CD3, —O*CH2D or —O*CHD2, or (C1-C15)alkyl or (C1-C15)alkylether substituted with -(R10)m;
• each R10 is independently halo, hydroxy, (C1-C5)alkoxy, —CO2H, —CO2(C2-C5)alkyl, —O-formyl or —NR11R12
• m is 0, 1, 2, 3, 4 or 5;
• R11 and R12 are each independently —H, formyl, —CO2H, —CO2(C2-C5)alkyl or —CO2CH2—(C6-C15)aryl;
• each R2 is independently —*CH3, —*CD3, —*CH2D or —*CHD2;
• n is an integer from 1 to 25, inclusive;
• each carbon atom indicated with an * is independently 12C or 13C;
• each carbon atom of a hydrolyzable formyl is independently 12C or 13C;
• and
• each hydrogen atom of a hydrolyzable formyl is H or D,
• provided:
• (i) when X is a covalent bond, there are at least two occurrences of X attached to a single carbon atom of R which are a covalent bond,
• (ii) if n is 1, then R is —H, -D, —O*CH3, —O*CD3, —O*CH2D or —O*CHD2, or the compound contains at least one hydrolyzable formyl,
• (iii) the compound is not dimethyladipate, trimethylorthoformate, trimethylorthoacetate, tetramethoxymethane, trimethoxymethane-d, trimethoxymethane-13C, (bis(methoxy-d3)methoxy-d)methane-d3, 1,1,1,2,2-pentamethoxypropane, 1,1,1,3,3,3-hexamethoxypropane, 1,1,1,4,4,4-hexamethoxybutane, 2,2,2-trimethoxyethan-1-amine, 1,1,1-trimethoxypropan-2-amine, 1,1,1-trichloro-2,2,2-trimethoxyethane or 1,1,1-trifluoro-2,2,2-trimethoxyethane, or a salt of the foregoing, and
• (iv) R is not —H or -D when X is —C(O)— and n is 1.

A compound of Structural Formula II:

• or a pharmaceutically acceptable salt thereof, wherein:
• R is H or D, or (C1-C15)alkyl substituted with -(R20)m;
• each R20 is independently halo, hydroxy, —OR2, (C2-C5)alkoxy, —CO2H, —CO2R2, —CO2(C2-C5)alkyl, —O-formyl or —NR21R22;
• m is 0, 1, 2, 3, 4 or 5;
• R21 and R22 are each independently —H, formyl, —CO2H, —CO2R2, —CO2(C2-C5)alkyl or —CO2CH2—(C6-C15)aryl;
• each R2 is independently —*CH3, —*CD3, —*CH2D or —*CHD2;
• p is an integer from 1 to 10, inclusive;
• each carbon atom indicated with an * is independently 12C or 13C;
• each carbon atom of a hydrolyzable formyl is independently 12C or 13C;
• and
• each hydrogen atom of a hydrolyzable formyl is H or D,
• provided the compound is not trimethylorthoformate, trimethoxymethane-d, trimethoxymethane-13C, (bis(methoxy-d3)methoxy-d)methane-d3, trimethylorthoacetate, 1,1,1,2,2-pentamethoxypropane, 1,1,1,3,3,3-hexamethoxypropane, 1,1,1,4,4,4-hexamethoxybutane, 2,2,2-trimethoxyethan-1-amine, 1,1,1-trimethoxypropan-2-amine, 1,1,1-trichloro-2,2,2-trimethoxyethane or 1,1,1-trifluoro-2,2,2-trimethoxyethane, or a salt of any of the foregoing.