Mikanolide derivatives, their preparation and therapeutic uses

A compound of the formula:

• corresponding to sub-formulae:
• wherein
• R1 is selected from the group consisting of hydrogen, —SR4 and —NR4R5;
• R2 is —SR6 or —NR6R7;
• R3 is selected from the group consisting of OH, —O(CO)R14, —OSiR15R16 R17, —O(CO)OR18 and —O(CO)NHR18;
• R4 and R6 are individually selected from the group consisting of, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, aryl and aralkyl optionally substituted on the aryl by at least one member of the group consisting of alkyl, hydroxy and alkoxy,
• R5 and R7 are individually selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, aryl and aralkyl optionally substituted on the aryl by at least one member of the group consisting of alkyl, hydroxy and alkoxy or R4 and R5 form together with the nitrogen atom which carries them a heterocycle with 5 to 7 ring members the additional member being selected from the group consisting of —CR8R9—, —NR10—, —O— and —S—, it being understood that there can only be one member chosen from —O— or —S— in said heterocycle,
• or R6 and R7 form together with the nitrogen atom which carries them a heterocycle with 5 to 7 ring members, the additional member being selected from the group consisting of —CR11R12—, —NR13—, —O— and —S— it being understood however that there can only be one member chosen from —O— or —S— in said heterocycle,
• R8, R10, R11 and R13 are individually hydrogen, alkyl, alkoxycarbonyl and aralkyl,
• R9 and R12 are individually hydrogen or alkyl or each of R9 and R12 being able to form respectively together with R8 and R11—O—(CH2)2—O— attached on either side to the carbon atom which carries it, such a radical only being present once at most per NR4R5 or NR6R7
• R14 is selected from the group consisting of alkyl, cycloalkyl, adamantyl, aryl, heteroaryl, aralkyl and heteroaralkyl optionally substituted on the aryl or heteroaryl by at least one member of the group consisting of halogen, alkyl, haloalkyl, nitro, hydroxy, alkoxy, alkylthio and phenyl;
• or R14 is such that R14—COOH is a natural amino acid or the optical enantiomer of such an amino acid;
• R15, R16 and R17 are individually alkyl, or phenyl;
• R18 is selected from the group consisting of alkyl, cycloalkyl, adamantyl, aryl, heteroaryl, aralkyl and heteroaralkyl optionally substituted on the aryl or heteroaryl by at least one member of the group consisting of halogen, alkyl, haloalkyl, nitro, hydroxy, alkoxy, alkylthio and phenyl;
• it being understood however that when the compounds correspond to sub-formula (I)2, then R1 is not hydrogen;
• or a pharmaceutically acceptable salt thereof.