Cyclosporin alkyne analogues and their pharmaceutical uses

1. A compound of Formula I:

wherein:

X is OH or OAc;

R 0 is H, CH 2 OH, or CH 2 OR 3 ;

R 1 is hydrogen, deuterium, or methyl;

R 2 is selected from the group consisting of:

hydrogen;

halogen;

C 1 -C 6 saturated or unsaturated, straight or branched carbon chain;

C 1 -C 6 saturated or unsaturated, straight or branched carbon chain containing a substitution or substitutions selected from the group consisting of deuterium, halogen, nitrogen, sulfur, and silicon;

C 1 -C 6 saturated or unsaturated, straight or branched carbon chain containing a function group or function groups selected from the group consisting of alcohol, ether, aldehyde, ketone, carboxylic acid, ester, and amide;

C 1 -C 6 saturated or unsaturated, straight or branched carbon chain containing a function group of oxime or hydrazone;

C 1 -C 6 saturated or unsaturated, straight or branched carbon chain containing an aryl or a heteroaryl group;

C 3 -C 6 substituted and unsubstituted cycloalkyl;

substituted and unsubstituted aryl; and

substituted and unsubstituted heteroaryl; and

R 3 is selected from the group consisting of:

alkanoyl,

alkenoyl,

alkynoyl,

aryloyl,

arylalkanoyl,

alkylaminocarbonyl,

arylaminocarbonyl,

arylalkylaminocarbonyl,

alkyloxycarbonyl,

aryloxycarbonyl, and

arylalkyloxycarbonyl,

wherein the compound is a cis geometric isomer, a trans geometric isomer, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein X is OH or OAc, R 0 is H, CH 2 OH, or CH 2 OAc, and R 1 is H or D.

3. The compound according to claim 2 , wherein R 2 is H.

4. The compound according to claim 2 , wherein R 2 is selected from the group consisting of CH 3 , CD 3 , CH 2 CH 3 , and CH 2 CH 2 CH 3 .

5. The compound according to claim 2 , wherein R 2 is selected from the group consisting of CH═CH 2 , CH═CHCH 3 , C≡CH, and —C≡C—CH 3 .

6. The compound according to claim 2 , wherein R 2 is selected from the group consisting of F, Cl, Br, and I.

7. The compound according to claim 2 , wherein R 2 is cyclopropyl.

8. The compound according to claim 2 , wherein R 2 is selected from the group consisting of CH 2 OH, CH(OH)CH 3 , CH 2 OCH 3 , CH 2 OCH 2 CH 3 , CHO, and C(═O)CH 3 .

9. The compound according to claim 2 , wherein R 2 is selected from the group consisting of CH═N—OCH 3 , CH═N—OCH 2 CH 3 , CH═N—NHCH 3 , and CH═N—N(CH 3 ) 2 .

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1 .