Claims
- 1. A process for the preparation of compounds of Formula I
- 2. The process of claim 1 wherein the compound of Formula II has the structure
- 3. The process of claim 1 wherein the carbodiimide reagent of Formula VI is 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI.HCl) or dimethylaminopropyl or 1,3-dicyclohexylcarbodiimide (DCC).
- 4. The process of claim 3 wherein the carbodiimide reagent of Formula VI is EDCI.HCl.
- 5. A compound of Formula VII
- 6. The compound of claim 5 having the structure
- 7. A process for the preparation of a compound of Formula VII
- 8. A process for the preparation of compounds of Formula I having the structure disclosed in claim 1 comprising reacting a compound of Formula VII having the structure disclosed in claim 1 with N-methyl-L-alanine to form a compound of Formula I.
- 9. A compound of Formula I prepared by the process of claim 8.
- 10. A cell-binding agent/maytansinoid complex prepared by converting a compound of Formula VII having the structure disclosed in claim 5 into the cell-binding agent/maytansinoid complex.
- 11. A cell-binding agent/maytansinoid complex prepared by a process comprising the following steps:
(1) esterifying maytansinol with a compound of Formula I prepared by the process of claim 1 or claim 8 to form a disulfide-containing maytansinoid ester; (2) reducing the disulfide-containing maytansinoid ester prepared by step (1) to a thiol-containing maytansinoid; (3) introducing dithiopyridyl groups into a cell-binding agent; and (4) linking the thiol-containing maytansinoid produced by step (2) to the dithiopyridyl cell-binding agent of step (3) by a disulfide link.
- 12. The cell-binding agent/maytansinoid complex of claim 10 or 11 wherein the cell-binding agent is an antibody.
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/231,784, filed Sep. 12, 2000.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60231784 |
Sep 2000 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
10009381 |
Dec 2001 |
US |
Child |
10390252 |
Mar 2003 |
US |