US2007167606A1PendingUtilityA1

Polyethylene glycol aldehydes

52
Assignee: WON CHEE-YOUBPriority: Jul 24, 2002Filed: Mar 14, 2007Published: Jul 19, 2007
Est. expiryJul 24, 2022(expired)· nominal 20-yr term from priority
Inventors:Chee-Youb Won
C08G 65/324C08G 65/331C08G 65/329C08G 65/2624C08G 65/2615
52
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Claims

Abstract

Polyethylene glycol aldehyde compounds are provided. Methods of making and using such compounds, as well as chemical intermediates are also provided.

Claims

exact text as granted — not AI-modified
1 . A compound of formula (l):  
       R 1 —(CH 2 CH 2 O) n —CH 2 CH 2 —X—Y—NH—(CH 2 ) p —CHO  (I)  
     wherein 
 R 1  is a capping group,  
 X is O or NH,  
 Y is selected from the group consisting of  
                     
 Z is a side chain of an amino acid,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       2 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of halogen, epoxide, maleimide, orthopyridyl disulfide, tosylate, isocyanate, hydrazine hydrate, cyanuric halide, N-succinimidyloxy, sulfo-N-succinimidyloxy, 1-benzotriazolyloxy, 1-imidazolyloxy, p-nitrophenyloxy, and  
     
       
         
         
             
             
         
       
     
   
   
       3 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower alkoxy, lower cycloalkyl, lower alkenyl, aryl, and heteroaryl.  
   
   
       4 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, and benzyloxy.  
   
   
       5 . A compound according to  claim 2 , wherein R 1  is  
     
       
         
         
             
             
         
       
     
   
   
       6 . A compound according to  claim 1  having the formula (III):  
     
       
         
         
             
             
         
       
     
   
   
       7 . A compound according to  claim 1  having the formula (IV):  
     
       
         
         
             
             
         
       
     
   
   
       8 . A compound according to  claim 1  having the formula (V):  
     
       
         
         
             
             
         
       
     
   
   
       9 . A compound according to  claim 1  having the formula (VI):  
     
       
         
         
             
             
         
       
     
   
   
       10 . A compound of formula (Il):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a capping group,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       11 . A compound according to  claim 10 , wherein p is 3.  
   
   
       12 . A compound according to  claim 11 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, and benzyloxy.  
   
   
       13 . A compound according to  claim 11 , wherein m is from 1 to 14.  
   
   
       14 . A compound according to  claim 13 , wherein m is from 1 to 7.  
   
   
       15 . A compound according to  claim 14 , wherein m is from 1 to 4.  
   
   
       16 . A compound according to  claim 11 , wherein n is from 20 to 5,000.  
   
   
       17 . A compound according to  claim 16 , wherein n is from 50 to 2,500.  
   
   
       18 . A compound according to  claim 17 , wherein n is from 75 to 1,000.  
   
   
       19 . A compound according to  claim 10 , wherein p is 3, R 1  is methoxy, m is 1, and n is from 100 to 750.  
   
   
       20 . A compound according to  claim 10 , wherein p is 2.  
   
   
       21 . A compound according to  claim 20 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, or benzyloxy.  
   
   
       22 . A compound according to  claim 20 , wherein m is from 1 to 14.  
   
   
       23 . A compound according to  claim 22 , wherein m is from 1 to 7.  
   
   
       24 . A compound according to  claim 23 , wherein m is from 1 to 4.  
   
   
       25 . A compound according to  claim 20 , wherein n is from 20 to 5,000.  
   
   
       26 . A compound according to  claim 25 , wherein n is from 50 to 2,500.  
   
   
       27 . A compound according to  claim 26 , wherein n is from 75 to 1,000.  
   
   
       28 . A compound according to  claim 10 , wherein p is 2, R 1  is methoxy, m is 1, and n is from 100 to 750.  
   
   
       29 . A compound according to  claim 10 , wherein p is 1.  
   
   
       30 . A compound according to  claim 29 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, or benzyloxy.  
   
   
       31 . A compound according to  claim 29 , wherein m is from 1 to 14.  
   
   
       32 . A compound according to  claim 31 , wherein m is from 1 to 7.  
   
   
       33 . A compound according to  claim 32 , wherein m is from 1 to 4.  
   
   
       34 . A compound according to  claim 29 , wherein n is from 20 to 5,000.  
   
   
       35 . A compound according to  claim 34 , wherein n is from 50 to 2,500.  
   
   
       36 . A compound according to  claim 35 , wherein n is from 75 to 1,000.  
   
   
       37 . A compound according to  claim 10 , wherein p is 1, R 1  is methoxy, m is 1, and n is from 100 to 750.  
   
   
       38 . A compound of formula (VIII):  
     
       
         
         
             
             
         
       
     
     wherein 
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       39 . A compound according to  claim 38 , wherein m is from 1 to 14.  
   
   
       40 . A compound according to  claim 39 , wherein m is from 1 to 7.  
   
   
       41 . A compound according to  claim 40 , wherein m is from 1 to 4.  
   
   
       42 . A compound according to  claim 38 , wherein n is from 20 to 5,000.  
   
   
       43 . A compound according to  claim 42 , wherein n is from 50 to 2,500.  
   
   
       44 . A compound according to  claim 43 , wherein n is from 75 to 1,000.  
   
   
       45 . A compound according to  claim 38 , wherein p is 3, m is 1 and n is from 100 to 750.  
   
   
       46 . A compound of formula (IX):  
       R 1 —(CH 2 —CH 2 —O) n —CH 2   13  CH 2 —X—Y—NH—(CH 2 ) p —CH(OCH 2 —CH 3 ) 2   (IX)  
     wherein 
 R 1  is a capping group,  
 X is O or NH,  
 Y is selected from the group consisting of  
                     
 Z is a side chain of an amino acid,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       47 . A compound according to  claim 46 , wherein R 1 is selected from the group consisting of halogen, epoxide, maleimide, orthopyridyl disulfide, tosylate, isocyanate, hydrazine hydrate, cyanuric halide, N-succinimidyloxy, sulfo-N-succinimidyloxy, 1-benzotriazolyloxy, 1-imidazolyloxy, p-nitrophenyloxy, and  
     
       
         
         
             
             
         
       
     
   
   
       48 . A compound according to  claim 46 , wherein R 1  is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower alkoxy, lower cycloalkyl, lower alkenyl, aryl, and heteroaryl.  
   
   
       49 . A compound according to  claim 46 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, and benzyloxy.  
   
   
       50 . A compound according to  claim 46 , wherein R 1  is  
     
       
         
         
             
             
         
       
     
   
   
       51 . A compound according to  claim 46 , wherein m is from 1 to 14.  
   
   
       52 . A compound according to  claim 51 , wherein m is from 1 to 7.  
   
   
       53 . A compound according to  claim 52 , wherein m is from 1 to 4.  
   
   
       54 . A compound according to  claim 46 , wherein n is from 20 to 5,000.  
   
   
       55 . A compound according to  claim 54 , wherein n is from 50 to 2,500.  
   
   
       56 . A compound according to  claim 55 , wherein n is from 75 to 1,000.  
   
   
       57 . A compound according to  claim 46 , wherein R 1  is methoxy, p is 3, m is 1, and n is from 100 to 750.  
   
   
       58 . A compound of formula (X):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a capping group,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       59 . A compound according to  claim 58 , wherein R 1  is selected from the group consisting of halogen, epoxide, maleimide, orthopyridyl disulfide, tosylate, isocyanate, hydrazine hydrate, cyanuric halide, N-succinimidyloxy, sulfo-N-succinimidyloxy, 1-benzotriazolyloxy, 1-imidazolyloxy, p-nitrophenyloxy, and  
     
       
         
         
             
             
         
       
     
   
   
       60 . A compound according to  claim 58 , wherein R 1  is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower alkoxy, lower cycloalkyl, lower alkenyl, aryl, and heteroaryl.  
   
   
       61 . A compound according to  claim 58 , wherein R 1  is selected from the group consisting of methoxy, hydroxy, and benzyloxy.  
   
   
       62 . A compound according to  claim 58 , wherein R 1  is  
     
       
         
         
             
             
         
       
     
   
   
       63 . A compound according to  claim 62 , wherein m is from 1 to 14.  
   
   
       64 . A compound according to  claim 63 , wherein m is from 1 to 7.  
   
   
       65 . A compound according to  claim 64 , wherein m is from 1 to 4.  
   
   
       66 . A compound according to  claim 58 , wherein n is from 20 to 5,000.  
   
   
       67 . A compound according to  claim 66 , wherein n is from 50 to 2,500.  
   
   
       68 . A compound according to  claim 67 , wherein n is from 75 to 1,000.  
   
   
       69 . A compound according to  claim 58 , wherein R 1  is methoxy, p is 3, m is 1, and n is from 100 to 750.  
   
   
       70 . A compound of formula (XI):  
     
       
         
         
             
             
         
       
     
     wherein 
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       71 . A compound according to  claim 70 , wherein m is from 1 to 14.  
   
   
       72 . A compound according to  claim 71 , wherein m is from 1 to 7.  
   
   
       73 . A compound according to  claim 72 , wherein m is from 1 to 4.  
   
   
       74 . A compound according to  claim 70 , wherein n is from 20 to 5,000.  
   
   
       75 . A compound according to  claim 74 , wherein n is from 50 to 2,500.  
   
   
       76 . A compound according to  claim 75 , wherein n is from 75 to 1,000.  
   
   
       77 . A compound according to  claim 70 , wherein p is 3, m is 1 and n is from 100 to 750.  
   
   
       78 . A method of making a polyethylene glycol aldehyde comprising hydrolyzing a compound of formula (IX):  
       R 1 —(CH 2 —CH 2 —O) n —CH 2 CH 2 —X—Y—NH—(CH 2 ) p —CH—(OCH 2 —CH 3 ) 2   (IX) 
     to produce a polyethylene glycol aldehyde of formula (I):  
       R 1 —(CH 2 CH 2 O) n —CH 2 CH 2 —X—Y—NH—(CH 2 ) p —CHO  (I)  
     wherein 
 R 1  is a capping group,  
 X is O or NH,  
 Y is selected from the group consisting of  
                     
 Z is a side chain of an amino acid,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       79 . A method of making a polyethylene glycol aldehyde comprising hydrolyzing a compound of formula (X):  
     
       
         
         
             
             
         
       
     
     to produce a polyethylene glycol aldehyde of formula (II):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is a capping group,  
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       80 . A method according to  claim 79  wherein the compound of formula (X) is produced by reacting a compound of formula (XII):  
       R 1 —(CH 2 —CH 2 —O) n —CH 2 CH 2 —O—(CH 2 ) m —COOH  (XII)  
     with a compound of formula (XIII):  
       H 2 N—(CH 2 ) p —CH—(OCH 2 —CH 3 ) 2   (XIII).  
   
   
       81 . A method according to  claim 80  wherein the compound of formula (XII) is produced by hydrolyzing a compound of formula (XIV):  
       R 1 —O—(CH 2 —CH 2 —O) n —CH 2 CH 2 —O—(CH 2 ) m —COOR 3   (XIV)  
     wherein R 3  is a branched or unbranched C 1 -C 4  alkyl.  
   
   
       82 . A method according to  claim 81  wherein the compound of formula (XIV) is produced by reacting a compound of formula (XV):  
       R 1 —(CH 2 —CH 2 —O) n —CH 2 CH 2 —OH  (XV)  
     with a compound of formula (XVI):  
       R 2 —(CH 2 ) m —COOR 3   (XVI)  
     wherein R 2  is halogen.  
   
   
       83 . A method of making a polyethylene glycol aldehyde comprising hydrolyzing a compound of formula (XVII):  
     
       
         
         
             
             
         
       
     
     to produce a polyethylene glycol of formula (Vil):  
     
       
         
         
             
             
         
       
     
     wherein 
 m is from 1 to 17,  
 n is from 10 to 10,000, and  
 p is from 1 to 3.  
 
   
   
       84 . A method according to  claim 83  wherein the compound of formula (VIII) is produced by reacting a compound of formula (XVIII):  
       HOOC—(CH 2 ) m —O—CH 2 CH 2 —(CH 2 —CH 2 —O) n —CH 2 CH 2 —O—(CH 2 ) m —COOH  (XVIII)  
     with a compound of formula (XIX):  
       H 2 N—(CH 2 ) p —CH—(OCH 2 —CH 3 ) 2   (XIX).  
   
   
       85 . A method according to  claim 84  wherein the compound of formula (XVIII) is produced by hydrolyzing a compound of formula (XX):  
       R 3 OOC—(CH 2 ) m —CH 2 CH 2 —O—(CH 2 —CH 2 —O) n —CH 2 CH 2 —O—(CH 2 ) m —COOR 3   (XXI)  
     wherein R 3  is a branched or unbranched C 1 -C 4  alkyl.  
   
   
       86 . A method according to  claim 85  wherein the compound of formula (XX) is produced by reacting a compound of formula (XXI):  
       HO—CH 2 CH 2 —(CH 2 —CH 2 —O) n —CH 2 CH 2 —OH  (XXI)  
     with a compound of formula (XVI):  
       R 2 —(CH 2 ) m —COOR 3   (XVI)  
     wherein R 2  is halogen.

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