Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders

1. A method of treating a mammal with hepatitis C comprising:

administering to the mammal a therapeutically effective amount of a compound having the following formula:

wherein:

X is OH or OAc;

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

R 1 is selected from the group consisting of:

hydrogen;

halogen;

C 2 -C 6 saturated or unsaturated, straight or branched carbon chain;

C 2 -C 6 saturated or unsaturated, straight or branched carbon chain containing substitution or substitutions selected from the group consisting of deuterium, halogen, nitrogen, sulfur, and silicon atom or atoms;

C 2 -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 ester, and amide;

C 2 -C 4 saturated or unsaturated, straight or branched carbon chain containing an aryl or a heteroaryl;

C 3 -C 6 -substituted and unsubstituted cycloalkyl;

substituted and unsubstituted aryl;

substituted and unsubstituted heteroaryl;

—CH 2 OH;

—CHO;

—CH═N—OR 3 ; and

—CH═N—NR 3 R 4 ;

R 2 is selected from the group consisting of:

alkanoyl;

alkenoyl;

alkynoyl;

aryloyl;

arylalkanoyl;

alkylaminocarbonyl;

arylaminocarbonyl;

arylalkylaminocarbonyl;

alkyloxycarbonyl;

aryloxycarbonyl; and

arylalkyloxycarbonyl;

R 3 or R 4 are the same or different and independently selected from the group consisting of:

hydrogen;

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

C 3 -C 6 unsaturated straight or branched carbon chain;

C 3 -C 6 -substituted and unsubstituted cycloalkyl;

C 1 -C 4 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; and

arylalkyloxycarbonyl; and

R 3 together with R 4 results in the formation of a cyclic moiety of C 2 -C 6 optionally containing heteroatom or heteroatoms,

or a pharmaceutically acceptable salt thereof,

under conditions effective to treat hepatitis C.

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

3. The method according to claim 2 , wherein R 1 is H.

4. The method according to claim 2 , wherein R 1 is selected from the group consisting of F, Cl, Br, and I.

5. The method according to claim 2 , wherein R 1 is selected from the group consisting of CH═CH 2 , CH═CHCH 3 , CH═CHCH 2 CH 3 , C(CH 3 )═CH 2 , CH═CD 2 , CH═CHCD 3 , and CH═CDCD 3 , and wherein the carbon-carbon double bond is a cis or a trans geometric isomer.

6. The method according to claim 2 , wherein R 1 is selected from the group consisting of CH═CHF, CH═CHCl, CH═CHBr, CH═CHI, CH═CF 2 , and CH═CCl 2 , and wherein the carbon-carbon double bond is a cis or a trans geometric isomer.

7. The method according to claim 2 , wherein R 1 is selected from the group consisting of C≡CH, C≡CCH 3 , C≡CCD 3 , C≡CCH 2 CH 3 , C≡CCH 2 CH 2 CH 3 , and C≡C-cyclopropyl.

8. The method according to claim 2 , wherein R 1 is selected from the group consisting of CH 2 C≡CH, CH 2 C≡CCH 3 , CH 2 C≡CCH 2 CH 3 , CH 2 CH═CH 2 , CH 2 CH═CHCH 3 , and CH 2 CH═CHCH 2 CH 3 , and wherein the carbon-carbon double bond is a cis or a trans geometric isomer.

9. The method according to claim 2 , wherein R 1 is selected from the group consisting of C≡C—C≡CH, C≡C—C≡CCH 3 , C≡CCH═CH 2 , C≡CCH═CHCH 3 , CH═CHC≡CH, CH═CHC≡CCH 3 , CH═CHCH═CH 2 , and CH═CHCH═CHCH 3 , and wherein the carbon-carbon double bond is a cis or a trans geometric isomer.

10. The method according to claim 2 , wherein R 1 is cyclopropyl.

11. The method according to claim 2 , wherein R 1 is selected from the group consisting of CH 2 OH, —CHO, CH(OH)CH 3 , C(═O)CH 3 , CH═N—OCH 3 , CH═N—OCH 2 CH 3 , CH═N—NHCH 3 , and CH═N—N(CH 3 ) 2 .

12. The method according to claim 1 , wherein said compound is administered in combination with an interferon.

13. The method according to claim 12 , wherein the interferon is interferon α2a or interferon α2b.

14. The method according to claim 12 , wherein the interferon is a pegylated interferon.

15. The method according to claim 14 , wherein the pegylated interferon is pegylated interferon α2a or pegylated interferon α2b.

16. The method according to claim 1 , wherein the compound is non-immunosuppressive.