06180095 is referenced by 64 patents and cites 15 patents.

The present invention is directed to double prodrugs containing polymeric-based transport forms. These polymeric prodrugs are preferably of the formula:

wherein:

L

1

is a bifunctional linking moiety;

G is H or

where

B is H, a leaving group, a residue of an amine-containing moiety, or a residue of a hydroxyl-containing moiety;

Y

1-4

are independently, O, S, or NR

12

;

R

1

, R

4

, R

9

, R

10

, and R

12

, are independently selected from the group consisting of hydrogen, C

1-6

alkyls, C

3-12

branched alkyls, C

3-8

cycloalkyls, C

1-6

substituted alkyls, C

3-8

substituted cycloalkyls, aryls, substituted aryls, aralkyls, C

1-6

heteroalkyls, substituted C

1-6

heteroalkyls;

R

2

, R

3

, R

5

and R

6

are independently selected from the group consisting of hydrogen, C

1-6

alkyls, C

1-6

alkoxy, phenoxy, C

1-8

heteroalkyls, C

1-8

heteroalkoxy, substituted C

1-6

alkyls, C

3-8

cycloalkyls, C

3-8

substituted cycloalkyls, aryls, substituted aryls, aralkyls, halo-, nitro-, cyano-, carboxy-, C

1-6

carboxyalkyls and C

1-6

alkyl carbonyls;

Ar is a moiety which when included in Formula (I) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heterocyclic group;

(m), (r), (s), (t), (u) and (v) are independently zero or one;

(p) is zero or a positive integer; and

R

11

is a substantially non-antigenic polymer.

The first prodrug is generated when the polymeric portion of the double prodrug is cleaved and the parent molecule is generated rapidly thereafter in vivo, preferably as a result of 1,6 or 1,4 benzyl elimination-reaction. Methods of preparing the compounds and methods of treatment are also disclosed.

Title
Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
Application Number
9/183557
Publication Number
6180095 (B2)
Application Date
October 30, 1998
Publication Date
January 30, 2001
Inventor
Yun H Choe
Piscataway
NJ, US
Annapurna Pendri
Matawan
NJ, US
Richard B Greenwald
Somerset
NJ, US
Agent
Roberts & Mercanti
US
Assignee
Enzon
NJ, US
IPC
A61K 31/21
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