US2003013748A1PendingUtilityA1

Pharmaceutical compositions comprising tyrphostins

Assignee: NOTOX LTDPriority: Aug 14, 1996Filed: May 9, 2002Published: Jan 16, 2003
Est. expiryAug 14, 2016(expired)· nominal 20-yr term from priority
A61P 39/00A61K 31/277A61K 31/427A61K 31/415A61K 31/4406
42
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Claims

Abstract

Compounds useful for countering undesired toxic effects to cells, tissues or organs having formula (I) wherein: Ar is a group of formulae (i) or (ii), n is O or, when Ar has formula (i) above, then n may also be 1, R is CN, —GC(S)NH2, —C(O)NHR3 or, when R1 is 4—NO2 and R2 is H or 3—OH, then R may also be a group of formulae (iii), (iv), (v), (vi) where R3 is H, phenyl, phenyl(lower alkyl) or pyridylmethyl; R1 and R2 are each independently H, OH, NO2 or, when R is CN, also CH3, F, or CF3, provided that both R1 and R2 are simultaneously H.

Claims

exact text as granted — not AI-modified
1 . Pharmaceutical compositions for countering damage to cells or tissue comprising an effective amount of a compound of the general formula  
       
         
           
           
               
               
           
         
       
       wherein: 
 Ar is a group of the formulae  
                     
 n is 0 or, when Ar has the formula (i) above, then n may also be 1,  
 R is CN, —C(S)NH 2 , —C(O)NHR 3  or, when R 1  is 4-NO 2  and R 2  is H or 3-OH, then R may also be a group of the formula  
                     
 where R 3  is H, phenyl, phenyl(lower alkyl) or pyridylmethyl;  
 R 1  and R 2  are each independently H, OH, NO 2  or, when R is CN, also CH 3 , F, or CF 3 , provided that both R 1  and R 2  arc not simultaneously H, together with a pharmaceutically acceptable carrier.  
 
     
     
         2 . Pharmaceutical compositions according to  claim 1 , comprising a compound of formula I wherein R is CN, —C(S)NH 2 , —C(O)NHCH 2 C 6 H 5  or a group of the formula  
       
         
           
           
               
               
           
         
       
       and n is 0, R 1  is 4-NO 2  and R 2  is H.  
     
     
         3 . Pharmaceutical compositions according to  claim 1  or  2 , for countering damage caused by a cytotoxic drug.  
     
     
         4 . Pharmaceutical compositions according, to  claim 3  for countering damage caused by an anti-neoplastic drug.  
     
     
         5 . Pharmaceutical compositions according to  claim 3  or  4  comprising, an effective amount of a compounds of formula I in  claim 1 , in combination with a cytotoxic drug.  
     
     
         6 . Pharmaceutical compositions according to any one of claims  3 - 5 , wherein the drug is selected from the group consisting of cisplatin, doxorubicin, cyclophosphamide, mitomycin-C and 5-fluorouracil.  
     
     
         7 . A pharmaceutical composition according to any one of claims  1 - 6 , for countering, myelotoxicity and lymphotoxicity.  
     
     
         8 . Pharmaceutical compositions according to any of the preceding claims in a form suitable for intravenous administration.  
     
     
         9 . Pharmaceutical compositions according to any of the preceding claims in a form suitable for oral administration.  
     
     
         10 . Pharmaceutical compositions according to  claim 1  or  2 , for use in ex vivo preservation of cells, tissue or organ.  
     
     
         11 . Pharmaceutical compositions according to  claim 1  or  2 , for countering damage caused by an immune mediated or inflammatory response.  
     
     
         12 . A pharmaceutical composition according to any one of claims  1 - 10 , for countering undesired apoptosis.  
     
     
         13 . A method of treatment of an individual for countering damage to cells, tissue or organ, said method comprising administering to the individual an effective amount of a compound of the general formula  
       
         
           
           
               
               
           
         
       
       wherein: 
 Ar is a group of the formulae  
                     
 n is 0 or, when Ar has the formula (i) above, then n may also be 1,  
 R is CN, —C(S)NH 2 , —C(O)NHR 3  or, when R 1  is 4-NO 2  and R 2  is H or 3-OH, then R may also be a group of the formula  
                     
 where R 3  is H, phenyl, phenyl(lower alkyl) or pyridylmethyl;  
 R 1  and R 2  arc each independently H, OH, NO 2  or, when R is CN, also CH 3 , F, or CF 3 , provided that both R 1  and R 2  are not simultaneously H, together with a pharmaceutically acceptable carrier.  
 
     
     
         14 . A method according to  claim 13 , wherein in the compound of formula I, R is CN, —C(S)NH 2 , —C(O)NHCH 2 C 6 H 5  or a group of the formula  
       
         
           
           
               
               
           
         
       
       and n is 0, R 1  is 4-NO 2  and R 2  is H.  
     
     
         15 . A method according to  claim 13  or  14 , wherein the harmful agent is a cytotoxic drug.  
     
     
         16 . A method according to  claim 15 , wherein the anti-cytotoxic drug is an anti-neoplastic drug.  
     
     
         17 . A method according to  claim 16 , wherein the cytotoxic drug is selected from the group consisting of cisplatin, doxorubicin, cyclophosphamide, mitomycin-C and 5-fluorouracil.  
     
     
         18 . A method according to any one of claims  13 - 17 , for countering myelotoxicity and lymphotoxicity.  
     
     
         19 . A method according to  claim 12 , for counting undesired harmful effects of irradiation treatment.  
     
     
         20 . A method according to any one of  claims 13  to  19 , wherein the compound of formula I is administered in combination with the cytotoxic drug or irradiation treatment.  
     
     
         21 . A method according to any one of  claims 1  to  20 , wherein the compound of formula I is administered prior to the administration of the cytotoxic drug or the irradiation treatment.  
     
     
         22 . A method according to any one of  claims 13  to  21 , wherein the compound of formula I is administered intravenously.  
     
     
         23 . A method according to any one of  claims 13  to  21 , wherein the compounds of formula I is administered orally.  
     
     
         24 . A method according to  claim 13  or  14 , for countering damage caused by an immune mediated or inflammatory response.  
     
     
         25 . A method for ex vivo preservation of organ, tissue or cells comprising contacting the organ, tissue or cells en vivo with a compound of the general formula  
       
         
           
           
               
               
           
         
       
       wherein: 
 Ar is a group of the formulae  
                     
 n is 0 or, when Ar has the formula (i) above, then n may also be 1,  
 R is CN, —C(S)NH 2 , —C(O)NHR 3  or, when R 1  is 4-NO 2  and R 2  is H or 3-OH, then R may also be a group of the formula  
                     
 where R 3  is H, phenyl, phenyl(lower alkyl) or pyridylmethyl;  
 R 1  and R 2  are each independently H, OH, NO 2  or, when R is CN, also CH 3 , F, or CF 3 , provided that both R 1  and R 2  are not simultaneously H, together with a pharmaceutically acceptable carrier.  
 
     
     
         26 . Compound of the general formula  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar is a group of the formula  
                     
 n is 0, or, when Ar has the formula (i) above, then n may also be 1,  
 R is —CN, —C(S)NH 2 , —C(O)NHR 3  or, where R 1  is 4-NO 2  and R 2  is H, then R may also be a group of the formulae  
                     
 R 1  and R 2  are each independently H, OH, NO 2  or, when R is CN, also CH 3 , F or CF 3 ; and  
 R 3  is H, phenyl, phenyl(lower alkyl) or pyridylmethyl; with the provisos that: 
 a) when R is CN and n is 0, then 
 (aa) if one of R 1  and R 2  is H or OH, then the other cannot represent NO 2 ;  
 (ab) if one of R 1  and R 2  is H or F, then the other cannot represent H or F; and  
 
 b) when R 1  is 4-NO 2 , R 2  is H and n is 0, then R cannot represent —C(O)NH 2  or —C(S)NH 2 .  
 
 
     
     
         27 . Compound according to  claim 26 , wherein R is CN, —C(S)NH 2 , —C(O)NHCH 2 C 6 H 5  or a group of the formula  
       
         
           
           
               
               
           
         
       
       and n is O,R 1  is 4-NO 2 , R 2  is H and n is 0.

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