Heterobifunctional poly(ethylene glycol) containing acid-labile amino protecting groups and uses thereof

• US 8,212,083 B2
• Filed: 04/27/2007
• Issued: 07/03/2012
• Est. Priority Date: 04/27/2006
• Status: Active Grant

• Current Assignee: Intezyne Technologies
• Original Assignee: Intezyne Technologies
• Inventors: Breitenkamp, Kurt, Sill, Kevin N., Skaff, Habib
• Primary Examiner(s): Katakam, Sudhakar
• Application Number:
  US11/796,392
• Publication Number:
  US 20080188638A1
• Time in Patent Office: 1,894 Days
• Field of Search: None
• US Class Current: 568/583
• CPC Class Codes: C07D 273/01 having one nitrogen atom
• CPC Class Codes: C07F 9/36 Amides thereof
• CPC Class Codes: C07F 9/46 Phosphinous acids [R2POH], [R2P(= O)H]: Thiophosphinous acids including[R2PSH]; [R2P(=S)H]; Aminophosphines [R2PNH2]; Derivatives thereof
• CPC Class Codes: C07F 9/572 Five-membered rings
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C08G 65/2612 containing aromatic or arylaliphatic hydroxyl groups
• CPC Class Codes: C08G 65/2624 containing aliphatic amine groups
• CPC Class Codes: C08G 65/263 containing heterocyclic amine groups
• CPC Class Codes: C08G 65/325 containing nitrogen
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/3344 containing oxygen in addition to sulfur
• CPC Class Codes: C08G 65/337 containing other elements organic compounds containing halogens only as halides of a carboxyl group C08G65/332
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention provides bifunctional polymers, methods of preparing the same, and intermediates thereto. These compounds are useful in a variety of applications including the PEGylation of biologically active molecules. The invention also provides methods of using said compounds and compositions thereof.

Claims

1. A compound of formula I:

2. The compound according to claim 1, wherein:

L² is -Cy-, —

C(O)—

, —

C(O)NH—

, —

NH—

O—

, —

O-Cy-CH₂NH—

O—

, —

NHC(O)—

, —

OCH₂—

, —

OCH₂C(O)—

, —

OCH₂CH₂C(O)—

, —

OCH₂CH₂O—

, —

OCH₂CH₂S—

, —

OCH₂CH₂C(O)O—

, —

OCH₂CH₂NH—

, —

OCH₂CH₂NHC(O)—

, —

OCH₂CH₂C(O)NH—

, —

O-Cy-, —

O-Cy-NH—

, —

NHC(O)CH₂CH₂C(O)O—

, —

OCH₂CH₂NHC(O)CH₂CH₂C(O)O—

, —

O-Cy-CH₂—

, —

OCH₂CH₂NHC(O)CH₂OCH₂C(O)O—

, —

OCH₂CH₂NHC(O)CH₂OCH₂C(O)NH—

, —

CH₂C(O)NH—

, —

CH₂C(O)NHNH—

, —

OCH₂CH₂NHNH—

, —

OC(O)CH₂CH₂CH₂CH₂—

, —

OCH₂CH₂—

, —

NHC(O)CH₂CH₂—

, —

NHC(O)CH₂CH₂CH₂—

, —

OC(O)CH₂CH₂CH₂—

, —

O-Cy-C(O)—

, —

O-Cy-C(O)O—

, —

O-Cy-C(O)O—

Cy-, —

O-Cy-OCH₂CH(CH₃)C(O)O—

, —

O-Cy-C(O)O—

, —

O-Cy-OCH(CH₃)CH₂C(O)O—

, —

OCH₂C(O)O—

, —

OCH₂C(O)NH—

, —

OCH₂O—

, —

OCH₂S—

, —

O-Cy-S—

, or —

OCH₂NH—

.

3. The compound according to claim 1, wherein R² is an azide-containing group, an alkyne-containing group, a group comprising a terminal alkyne moiety, an aldehyde-containing group, a group comprising a terminal hydrazine moiety, a group comprising a terminal oxyamine moiety, an epoxide-containing group, or a group comprising a terminal maleimide moiety.

4. The compound according to claim 1, wherein said compound is selected from the following formulae:

5. The compound of claim 1, selected from those depicted in Tables A and B: