Purine derivatives having, in particular, anti-proliferative properties, and their biological uses

Abstract

This invention provides 2-, 6, and 9-substituted purine derivatives, particularly 2(1-R hydroxymethylpropylamino)-6-benzylamino-9-isopropyl purine, having, in particular, antiproliferative properties, and suitable for use as pharmaceutical compositions and herbicidal compositions. Also provided are pharmaceutical compositions and herbicidal compositions comprising the 2-, 6, and 9-substituted purine derivatives, and methods of treatment using the 2-, 6, and 9-substituted purine derivatives.

1 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 2  is R—NH, wherein R is a straight or branched alkyl or alkenyl; 
 R 6  is benzylamino; 
 R 9  is a straight or branched alkyl or alkenyl, excluding methyl; and 
 each optionally substituted by one or more hydroxy, halogen, amino or alkyl groups, and 
 
     wherein said compound has an IC 50  less than or equal to 1 μM for cdc2/cyclin B. 
   
   
       2 - 28 . (canceled) 
   
   
       29 . The compound of  claim 1 , wherein said compound is in the form of an optical isomer, a racemic mixture or a geometric isomer. 
   
   
       30 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  and a pharmaceutical vehicle. 
   
   
       31 . A method of treating a proliferative disorder or a tumor in a patient, comprising administering to said patient the pharmaceutical composition of  claim 30 . 
   
   
       32 . The method according to  claim 31 , wherein said proliferative disorder is selected from the group consisting of cancer, psoriasis, parasitoses, Alzheimer's disease, and neuronal apoptosis. 
   
   
       33 . The method according to  claim 31 , wherein said pharmaceutical composition is administered orally or parenterally. 
   
   
       34 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 2  is R—NH, wherein R is a straight or branched alkyl or a heterocyclic alkyl; 
 R 6  is benzylamino; 
 R 9  is a straight or branched alkyl or alkenyl, excluding methyl; and each optionally substituted by one or more hydroxy, halogen, amino or alkylhydroxy groups. 
 
   
   
       35 . The compound according to  claim 34 , wherein R 2  is a pyrrolidin-1-yl group. 
   
   
       36 . The compound according to  claim 35 , wherein R 2  is a 2-hydroxyalkyl-pyrrolidin-1-yl group. 
   
   
       37 . The compound of  claim 36 , where R 2  is selected from the group consisting of 2-hydroxymethyl-pyrrolidin-1-yl, 2-hydroxyethyl-pyrrolidin-1-yl, 2-hydroxypropyl-pyrrolidin-1-yl, 2-hydroxybutyl-pyrrolidin-1-yl, 2-hydroxypentyl-pyrrolidin-1-yl, 2-hydroxyhexyl-pyrrolidin-1-yl. 
   
   
       38 . The compound of  claim 34 , wherein R 2  is an aminoalkylamino group. 
   
   
       39 . The compound of  claim 31 , wherein R 2  is an aminoethylamino group or an aminopropylamino group. 
   
   
       40 . The compound of  claim 34 , wherein R 9  is isopropyl or cyclopentyl. 
   
   
       41 . The compound of  claim 34 , wherein said compound is in the form of an optical isomer, a racemic mixture or a geometric isomer. 
   
   
       42 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 34  and a pharmaceutical vehicle. 
   
   
       43 . A method of treating a proliferative disorder or a tumor in a patient, comprising administering to said patient the pharmaceutical composition of  claim 42 . 
   
   
       44 . The method according to  claim 43 , wherein said proliferative disorder is selected from the group consisting of cancer, psoriasis, parasitoses, Alzheimer's disease, and neuronal apoptosis. 
   
   
       45 . The method according to  claim 43 , wherein said pharmaceutical composition is administered orally or parenterally. 
   
   
       46 . A compound selected from the group consisting of 2-(3-hydroxypropylamino)-6-benzylamino-9-isopropyl purine, 2-D,L-(2-hydroxypropylamino)-6-benzylamino-9-isopropyl purine, 2-(aminoethylamino)-6-benzylamino-9-isopropyl purine, 2-(2-hydroxypropyl-amino)-6-isopentenylamino-9-isopropyl purine, non-crystalline 6-benzylamino-2-[(2R)-2-hydroxymethyl-pyrrolidine-1-yl]-9-isopropyl-(9H)-purine, 2-[6-benzylamino-9-isopropyl-(9H)-purine-2-yl]-N-benzylaminoethanol, 2-(6-(benzylamino)-9-isopropyl-9H-purin-2-ylamino)hexan-1-ol, 2-(S)-[6-benzylamino-9-isopropyl-(9H)-purine-2-yl]-amino-2-phenylethanol, 2-(R)-[6-benzylamino-9-isopropyl-(9H)-purine-2-yl]-amino-2-phenylethanol, 2-(R)-[6-benzylamino-9-isopropyl-(9H)-purine-2-yl]-amino-3-phenylpropanol, (1-(6-(benzylamino)-9-cyclopentyl-9H-purin-2-yl)pyrrolidin-2-yl)methanol, and an optical isomer, a racemic mixture, and a geometric isomer thereof. 
   
   
       47 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 46  and a pharmaceutical vehicle. 
   
   
       48 . A method of treating a proliferative disorder or a tumor in a patient, comprising administering to said patient the pharmaceutical composition of  claim 46 . 
   
   
       49 . The method according to  claim 48 , wherein said proliferative disorder is selected from the group consisting of cancer, psoriasis, parasitoses, Alzheimer's disease, and neuronal apoptosis. 
   
   
       50 . The method according to  claim 48 , wherein said pharmaceutical composition is administered orally or parenterally.