Quinazoline derivative

• US 5,952,333 A
• Filed: 09/26/1997
• Issued: 09/14/1999
• Est. Priority Date: 04/27/1995
• Status: Expired due to Fees

• Current Assignee: Astrazeneca UK Limited (Astrazeneca PLC)
• Original Assignee: Zeneca Incorporated (Astrazeneca PLC)
• Inventors: Barker, Andrew John
• Primary Examiner(s): Ford, John M.
• Application Number:
  US08/930,044
• Time in Patent Office: 718 Days
• Field of Search: 544/293, 514/259
• US Class Current: 514/266.4
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 239/94 Nitrogen atoms

Abstract

The invention concerns the quinazoline derivative 6-(2-methoxyethylamino)-7-methoxy-4-(3'"'"'-methylanilino)quinazoline, or a pharmaceutically-acceptable salt thereof, processes for its preparation, pharmaceutical compositions containing the compound and the use of the receptor tyrosine kinase inhibitory properties of the compound in the treatments of proliferative disease such as cancer.

Claims

1. The quinazoline derivative 6-(2-methoxyethylamino)-7-methoxy4-(3'"'"'-methylanilino)-quinazoline;

or a pharmaceutically-acceptable salt thereof.

2. A process for the preparation of the quinazoline derivative as claimed in claim 1 which comprises:

(a) the reaction of a quinazoline of the formula I ##STR2## wherein Z is a displaceable group, with 3'"'"'-methylaniline;

(b) the alkylation of 6-amino-7-methoxy4-(3'"'"'-methylanilino)quinazoline with an alkylating agent of the formula ZCH₂ CH₂ OMe wherein Z is a displaceable group;

(c) the reductive amination of 2-methoxyacetaldehyde with 6-amino-7-methoxy4-(3'"'"'-methylanilino)quinazoline;

or

(d) the methylation of the compound 7-hydroxy-6-(2-hydroxyethylamino)-4-(3'"'"'-methylanilino)quinazoline 7-hydroxy-6-(2-methoxyethylamino)4-(3'"'"'-methylanilino)quinazoline or 6-(2-hydroxyethylamino)-7-methoxy4-(3'"'"'-methylanilino)quinazoline with a methylating agent of the formula Me-Z wherein Z is a displaceable group;

and when a pharmaceutically-acceptable salt of the quinazoline derivative is required it may be obtained by reaction of said compound with a suitable acid using a conventional procedure.

3. A pharmaceutical composition which comprises the quinazoline derivative 6-(2-methoxyethylamino)-7-methoxy4-(3'"'"'-methylanilino)quinazoline, or a pharmaceutically-acceptable salt thereof, in association with a pharmaceutically-acceptable diluent or carrier.

4. A method for producing an anti-proliferative effect in a warm-blooded animal in need of such treatment which comprises administering to said animal an effective amount of the quinazoline derivative 6-(2-methoxyethylamino)-7-methoxy-4-(3'"'"'-methylanilino)quinazoline, or a pharmaceutically-acceptable salt thereof.