Cyclosporin with improved activity profile

Abstract

The invention relates to a novel cyclosporin, the pharmaceutical use thereof and a pharmaceutical composition containing it.

1. Synthesised cyclosporin having the formula: 
                 
 
       wherein:
 X is -MeBmt or 6,7-dihydro-MeBmt-    U is -Abu, Nva, Val or Thr    Y is Sar or (D)-MeSer or (D)-MeAla or (D)-MeSer (OAcyl)    Z is (N-R)aa where aa={Val, Ile, Thr, Phe, Tyr, Thr (OAc), Thr (OG 1 ), Phe (G 2 ), PheCH 2 (G 3 ) or Tyr (OG 3 )} with R={alkyl>CH 3 };    G 1 ={phenyl-COOH, phenyl-COOMe or phenyl-COOEt};    G 2 ={CH 2 COOH, CH 2 COOMe(Et), CH 2 PO(OMe) 2  or CH 2 PO(OH) 2 };    G 3 ={PO(OH) 2 , PO(OCH 2 CH═CH 2 ) 2 , CH 2 COOH, CH 2 COOMe, or CH 2 COOEt}    
     
     
       2. Cyclosporin according to  claim 1 , wherein the residue Z in position 4 is (R)Val where R>CH 3  and R<C 10 H 11 . 
     
     
       3. Cyclosporin according to  claim 1 , wherein the residue Z in position 4 is N-ethyl-Valine. 
     
     
       4. Pharmaceutical composition containing the compound having the formula: 
                 
 
       wherein:
 X is -MeBmt or 6,7-dihydro-MeBmt-    U is -Abu, Nva, Val or Thr    Y is Sar or (D)-MeSer or (D)-MeAla or (D)-MeSer (OAcyl)    Z is (N-R)aa where aa={Val, Ile, Thr, Phe, Tyr, Thr (OAc), Thr (OG 1 ), Phe (G 2 ), PheCH 2 (G 3 ) or Tyr (OG 3 )} with R={alkyl>CH 3 };    G 1 ={phenyl-COOH, phenyl-COOMe or phenyl-COOEt};    G 2 ={CH 2 COOH, CH 2 COOMe(Et), CH 2 PO(OMe) 2  or CH 2 PO(OH) 2 };    G 3 ={PO(OH) 2 , PO(OCH 2 CH═CH 2 ) 2 , CH 2 COOH, CH 2 COOMe, or CH 2 COOEt}    
     
     
       5. Pharmaceutical composition according to  claim 4 , combined with a pharmaceutically acceptable solution. 
     
     
       6. A medicinal product for the treatment and prevention  of acquired immunodeficiency syndrome (AIDS) containing the cyclosporin according to  claim 1  or  claim 4  . 
     
     
       7. A medicinal product for the treatment and prevention of AIDS containing the cyclosporin according to  claim 3 . 
     
     
       8. The pharmaceutical composition according to  claim 4  for the treatment of acquired immunodeficiency syndrome AIDS.