Novel cyclosporin analogues and their pharmaceutical uses

A compound of Formula Ia:

• wherein:
• X is OH or OAc;
• R0 is H or CH2OR3;
• R1 is H or D;
• R2 is selected from the group consisting of:
• halogen,
• C1 and C6 halogenated saturated straight or branched carbon chain,
• C2-C6 halogenated unsaturated straight or branched carbon chain,
• C3-C6 unsubstituted cycloalkyl,
• C1-C6 saturated straight or branched carbon chain containing amino group,
• —CH═N—OR4, and
• —CH═N—NR4R5;
• R3 is selected from the group consisting of:
• hydrogen,
• alkanoyl,
• alkenoyl,
• alkynoyl,
• aryloyl,
• arylalkanoyl,
• alkylaminocarbonyl,
• arylaminocarbonyl,
• arylalkylaminocarbonyl,
• alkyloxycarbonyl,
• aryloxycarbonyl, and
• arylalkyloxycarbonyl;
• R4 and R5 are the same or different and independently selected from the group consisting of:
• hydrogen,
• C1-C6 saturated straight or branched carbon chain,
• C3-C6 unsaturated straight or branched carbon chain,
• C3-C6-substituted and unsubstituted cycloalkyl,
• C1-C4 carbon chain containing an aryl or heteroaryl,
• substituted and unsubstituted aryl,
• substituted and unsubstituted heteroaryl,
• alkanoyl,
• alkenoyl,
• alkynoyl,
• aryloyl,
• arylalkanoyl,
• alkylaminocarbonyl,
• arylaminocarbonyl,
• arylalkylaminocarbonyl,
• alkyloxycarbonyl,
• aryloxycarbonyl,
• arylalkyloxycarbonyl,
• alkylsulfonyl, and
• arylsulfonyl;
• and
• R4 together with R5 results in the formation of a cyclic moiety of C2-C6 optionally containing heteroatom or heteroatoms,
• wherein the compound is a cis geometric isomer, a trans geometric isomer, or a mixture of the cis and the trans geometric isomers or a pharmaceutically acceptable salt thereof.