Process for the preparation of cyclosporin derivatives

A method for preventing or treating a retrovirus infection, comprising administering to a mammal in need or desire thereof an effective amount of a cyclosporin derivative substituted at the 3-position having the formula:

• in which:
• 1) the radicals R1, R2, and R4 to R11, and Z1, Z2, and Z4 to Z11 are defined as for cyclosporin A and R3 is a radical —S-Alk-Ro in which:
• Alk is an alkylene radical comprising from 2 to 6 straight- or branched-chain carbon atoms or a cycloalkylene radical comprising from 3 to 6 carbon atoms;
• and
• Ro is
• a carboxyl or alkyloxycarbonyl radical;
• or
• an —NG1G2 radical in which G1 and G2, which are identical or different, are each
• a hydrogen atom;
• or
• a phenyl, cycloalkyl (C3-6), alkenyl (C2-4), or alkyl radical, each of which is optionally substituted by a halogen atom, an alkyloxy, alkyloxycarbonyl, amino, alkylamino, or dialkylamino radical;
• or
• a benzyl radical or a saturated or unsaturated heterocyclyl radical comprising 5 or 6 ring members and from 1 to 3 heteroatoms;
• or
• G1 and G2 form, with the nitrogen atom to which they are attached, a saturated or unsaturated heterocycle comprising from 4 to 6 ring members which can comprise another heteroatom chosen from nitrogen, oxygen, and sulphur and which is optionally substituted by alkyl, phenyl, or benzyl;
• or
• a radical of formula:
• in which G1 and G2 are defined as above, G3 is a hydrogen atom or an alkyl radical, and n is an integer from 2 to 4, the alkyl portions or radicals defined above are straight or branched and comprise from 1 to 4 carbon atoms;
• or
• one or more hydroxyl groups and optionally one or more non-methylated nitrogen atoms at the α position and optionally any other deprotonatable acidic group present in said formula (IV) are optionally deprotonated or in the protected form.