Disulfide, sulfide, sulfoxide, and sulfone derivatives of cyclic sugars and uses

A process for preparing a compound of formula (I), a tautomer, a pharmaceutically acceptable salt, a prodrug or a solvate thereof:

• wherein:
• n is an integer of 0, 1, or 2,
• X represents —S(O)m— or a single bond, wherein m is an integer of 0, 1, or 2,
• and R represents hydrogen or is a residue Ra, which residue Ra is selected from the group consisting of:
• C1-6 alkyl;
• C2-6 alkenyl;
• C3-8 cycloalkyl;
• C3-8 cycloalkyl, wherein one CH2 group is replaced by O, S, N or NCH3;
• C4-8 cycloalkenyl;
• C4-8 cycloalkenyl, wherein one CH2 group is replaced by O, S, N or NCH3;
• phenyl;
• pyridyl;
• thiophenyl;
• nitrosyl;
• S-cysteinyl;
• S-glutathionyl;
• and
• wherein R* is selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C3-8 cycloalkyl;
• C4-8 cycloalkenyl, acetyloxy, hydroxyl, ONO2 and halogen,
• wherein Ra optionally is substituted by one to three groups independently selected from the group consisting of C1-6 alkyl, C2-6 alkeny, C3-8 cycloalkyl, C4-8 cycloalkenyl, acetyloxy, hydroxyl, ONO2 and halogen, which process comprises conducting the following steps:
• a) effecting the hydrolysis of a compound of formula (IIa):
• wherein R′ is C1-C6 alkyl, preferably methyl,
• to obtain the following compound:
• and
• (b) optionally, effecting on the compound prepared according to the step (a):
• I. an oxidation reaction to obtain:
• optionally followed by a second oxidation to obtain the following compound:
• wherein:
• n is 1 or 2,
• X is —S(O)m—, wherein m is 0, 1 or 2, and
• R* represents hydroxyl or ONO2;
• II. a substitution reaction to obtain:
• a compound according to formula (I), wherein:
• n is an integer of 0,
• X represents a bond,
• and R does not represent nitrosyl,
• optionally followed by an oxidation to obtain a compound according to formula (I), wherein:
• n is an integer of 0,
• X represents —S(O)m—, wherein m is an integer of 0 or 1,
• and R does not represent nitrosyl;
• III. a substitution reaction to obtain:
• a compound according to formula (I), wherein:
• n is an integer of 0, and
• X represents —S—;
• optionally followed by an oxidation to obtain a compound according to formula (I), wherein:
• n is an integer of 1 or 2, and
• X represents —S(O)m—, wherein m is 0, 1 or 2;
• or
• IV. a nitrosation reaction to obtain:

A process for preparing a compound of formula (11) or a tautomer, a pharmaceutically acceptable salt, a prodrug or a solvate thereof:

• which process comprises the following steps:
• a) effecting an oxidation of a compound of formula (III):
• wherein R′ is C1-C6 alkyl, preferably methyl, to obtain 2,2′-dithiodiisosorbide (10),
• and
• (b) effecting a nitration of the compound prepared in step (a) with a nitrating agent in the presence of a carboxylic anhydride, preferably acetic anhydride.