N-(pyrrolo(2,3-d)pyrimidin-3-ylacyl)-glutamic acid derivatives

• US 5,344,932 A
• Filed: 03/22/1991
• Issued: 09/06/1994
• Est. Priority Date: 12/11/1989
• Status: Expired due to Term

• Current Assignee: The Trustees of Princeton University (Princeton University)
• Original Assignee: The Trustees of Princeton University (Princeton University)
• Inventors: Taylor, Edward C.
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US07/674,541
• Time in Patent Office: 1,264 Days
• Field of Search: 544/280, 514/258
• US Class Current: 544/280
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

N-(Acyl)glutamic acid derivatives in which the acyl group is substituted with 4-hydroxypyrrolo[2,3-d]-pyrimidin-3-yl group are antineoplastic agents. A typical embodiment is N-[4-(2-{4-hydroxy-6-aminopyrrolo-[2,3-d]pyrimidin-3-yl}ethyl)benzoyl]-L-glutamic acid.

Claims

1. A compound of the formula:

##STR14## in which;

R¹ is --OH or --NH₂ ;

R² is hydrogen or a pharmaceutically acceptable cation;

R³ is 1,4-phenylene unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl;

R⁴ is hydrogen, or methyl;

R⁵ is amino; and

the configuration about the carbon atom designated * is S.

2. A compound according to claim 1 wherein R¹ is --OH;

R³ is 1,4-phenylene, and R⁴ is hydrogen.

3. The compound according to claim 1 which is N-{4-[2-(4-hydroxy-6-aminopyrrolo[2,3-d]pyrimidin-3-yl)ethyl]benzoyl}-L-glutamic acid.

4. The compound according to claim 1 which is N-{4-[1-hydroxy-3-(4-hydroxy-6-aminopyrrolo[2,3-d]pyrimidin-3-yl)prop-2-yl]benzoyl}glutamic acid.

5. The compound according to claim 1 which is N-{2-fluoro-4-[2-(4-hydroxy-6-aminopyrrolo[2,3-d]pyrimidin-3-yl)ethyl]benzoyl}-L-glutamic acid.

6. The compound according to claim 1 which is N-{3-fluoro-4-[2-(4-hydroxy-6-aminopyrrolo[2,3-d]pyrimidin-3-yl)ethyl]benzoyl}-L-glutamic acid.

7. A compound of the formula:

##STR15## in which;

R¹ is --OH or --NH₂ ;

R^2'"'"' is hydrogen, a pharmaceutically acceptable cation, or a carboxy protecting group;

R³ is 1,4-phenylene unsubstituted or substituted with chloro, fluoro, methyl, methoxy, or trifluoromethyl;

R^4'"'"' is hydrogen, or methyl;

R^5'"'"' is amino or amino substituted with an amino protecting group; and

the configuration about the carbon atom designated * is S.