Drug delivery systems

• US 5,716,990 A
• Filed: 09/09/1996
• Issued: 02/10/1998
• Est. Priority Date: 03/09/1987
• Status: Expired due to Fees

• Current Assignee: Cancer Research Campaign Technology Ltd (Cancer Research UK)
• Original Assignee: Cancer Research Campaign Technology Ltd (Cancer Research UK)
• Inventors: Bagshawe, Kenneth D., Springer, Caroline Joy, Jarman, Michael
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/709,740
• Time in Patent Office: 519 Days
• Field of Search: 562/430, 562/455, 514/562, 514/563, 514/517, 558/44, 558/47, 558/52, 558/53, 558/54, 564/138
• US Class Current: 514/517
• CPC Class Codes: A61K 47/6899 Antibody-Directed Enzyme Prodrug Therapy [ADEPT]
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Nitrogen mustard pro-drugs of the formula ##STR1## are disclosed where R is the residue of an α-amino acid RNH₂ and M is a disubstituted amino "mustard" group, useful in antibody directed enzyme pro-drug therapy in the treatment of cancer.

Claims

1. A nitrogen mustard pro-drug of the formula ##STR9## where R is a glutamic acid residue and M is a ##STR10## group.

2. A pro-drug according to claim 1 where R is a D-glutamic acid residue.

3. A process for preparing a compound as defined in claim 1 which comprises reacting a nitrogen mustard of formula ##STR11## or a reactive carboxy derivative thereof with a carboxy protected amino acid R NH₂ and removing the carboxy protecting group.

4. A process for preparing a compound as defined in claim 1 which comprises reacting a compound of the formula:

##STR12## with a reagent capable of replacing the HO group by Cl, CH₃ SO₃ or CF₃ SO₃.

5. A pharmaceutical composition comprising a pro-drug according to claim 1 or 2 together with a pharmaceutically acceptable carrier or diluent.

6. A composition according to claim 5 suitable for intravenous administration.