Conjugates of pyrrolo[1,4]benzodiazepine dimers as anticancer agents

• US 8,481,042 B2
• Filed: 02/24/2012
• Issued: 07/09/2013
• Est. Priority Date: 08/25/2009
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Commercon, Alain, Gauzy-Lazo, Laurence
• Primary Examiner(s): Ha, Julie
• Assistant Examiner(s): DABKOWSKI, ERINNE R
• Application Number:
  US13/404,872
• Publication Number:
  US 20120244172A1
• Time in Patent Office: 501 Days
• Field of Search: None
• US Class Current: 424/181.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention relates to pyrrolo[1,4]benzodiazepine (PBD) dimer conjugates, to the compositions comprising them and to their therapeutic application, in particular as anticancer agents. The invention also relates to the process for the preparation of the conjugates, to their application as anticancer agents and to the dimers themselves.

Claims

1. A compound of according to formula (I):

2. A compound according to claim 1, wherein said compound according to formula:

3. A compound according to claim 1, wherein said compound is according to formula (IA) or (IB):

4. A compound according to claim 1, wherein each of Y and Y′

represent, independently, a (C₁-C₄)alkoxy group, more particularly a methoxy group;

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1, wherein L is:

6. A compound according to claim 1, wherein L is:

7. A compound according to claim 1, wherein L is:

8. A compound according to claim 1, wherein —

COZ_bR_b represents —

COOH, —

COO(C₁-C₆)alkyl, —

COOCH₃, —

COOCH₂CH═

CH₂,

9. A compound according to claim 1, wherein said compound is:

10. Pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and at least one excipient.

11. A compound according to claim 1, wherein I represents an integer ranging from 1 to 20;

or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 1, wherein represents an integer ranging from 1 to 10;

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 4, wherein each of Y and Y′

represent a methoxy group;

or a pharmaceutically acceptable salt thereof.