Melvinolin derivatives

A compound of formula I

• wherein
• each of a - - - b and α - - - β independently, is either a single bond or a double bond;
• R1 is
• H, C1-4alkyl or ORa
• wherein Ra is H, C1-6alkyl optionally substituted by OH or C1-4alkoxy, C2-6alkenyl or aryl-C1-4alkyl;
• R2 is OH;
• —O—CO—R5 wherein R5 is C1-8alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-4alkyl, aryl or aryl-C1-4alkyl;
• or —O—R6 wherein R6 is the residue of an α-amino-acid attached to O through its carbonyl residue or —CHR7—COR8 wherein R7 is H, C1-4alkyl, heteroC1-4alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-4alkyl, aryl or aryl-C1-4alkyl and R6 is OH, C1-4alkoxy or NR9R10 wherein each of R9 and R10 independently is H, C1-4alkyl or R9 and R10 form together with the nitrogen to which they are bound, a heteroaryl group;
• R3 is a substituted linear amino alcohol or cyclic carbamate of formula (c2);
• wherein
• each of R50, independently is H;
• C1-8alkyl;
• C3-7cycloalkyl;
• aryl;
• C3-7cycloalkyl-C1-4alkyl;
• aryl-C1-4alkyl;
• heteroaryl;
• heteroaryl-C1-4alkyl;
• C1-4alkylcarbonyl;
• aryl-carbonyl;
• heteroaryl-carbonyl;
• aryl-C1-4alkyl-carbonyl or heteroaryl-C1-4alkyl-carbonyl, and
• each of R51, independently is H;
• C1-4alkyl;
• hydroxy-C1-4alkyl;
• amino-C1-4alkyl;
• C1-4alkoxy-C1-4alkyl;
• C1-4alkoxy-carbonyl-C1-4alkyl wherein C1-4alkoxy is optionally substituted by amino, C1-4alkyl-amino or di-(C1-4alkyl)amino;
• HOOC—C1-4alkyl;
• or R23R24N—CO—C1-4alkyl wherein R23 is H, C1-4alkyl, hydroxy-C1-4alkyl, polyhydroxy-C1-8alkyl, heteroaryl, heteroaryl-C1-4alkyl, amino-C1-4alkyl, C1-4alkylamino-C1-4alkyl, di-(C1-4alkyl)amino-C1-4alkyl or aryl-C1-4alkyl and R24 is H, C1-4alkyl or hydroxy-C1-4alkyl, at least one of R50 and R51 being other than H,
• each of X and Y is H or X and Y form together
• each of a - - - b and α - - - β being a single bond when each of R13 or R14 is OH;
• and
• R4 is H or OR19 wherein R19 is C1-6alkyl, hydroxy-C1-6alkyl, C1-4alkoxy-C1-6alkyl, aryl-C1-4alkyl or C1-4alkoxycarbonyl-C1-4alkyl,
• and wherever “aryl” appears as is or in the significances of “aryl-C1-4alkyl” in the above definition, it is “phenyl” or “naphthyl” optionally substituted by halogen, OH, NR11R12, COOH, CF3, C1-4alkoxy, C1-4alkyl, hydroxy-C1-4alkyl, hydroxy-C1alkoxy, C1-4alkoxy-carbonyl, cyano or CONR11R12, each of R11 and R12 independently being H, C1-4alkyl, phenyl, naphthyl, phenyl-C1-4alkyl or naphthyl-C1-4alkyl or R11 and R12 together with the nitrogen to which they are bound forming heteroaryl;
• and wherever “heteroaryl” appears, it is a 5- or 6-membered heteroaryl optionally fused to a benzene ring;
• in free form or in salt form.