Quinazoline derivatives as VEGF inhibitors

• US 9,040,548 B2
• Filed: 01/03/2014
• Issued: 05/26/2015
• Est. Priority Date: 11/05/1999
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Thomas, Andrew Peter, Stokes, Elaine Sophie Elizabeth, Hennequin, Laurent Francois Andre
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US14/146,954
• Publication Number:
  US 20140121228A1
• Time in Patent Office: 508 Days
• Field of Search: 514/266.1, 514/266.2, 544/283, 544/284
• US Class Current: 514/266.2
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention relates to quinazoline derivatives of formula (I),

wherein m is an integer from 1 to 3; R¹ represents halogeno or C_1-3alkyl; X¹ represents —O—; R² is selected from one of the following three groups: 1) C_1-5alkylR³, wherein R³ is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C_1-4alkyl, C_1-4hydroxyalkyl and C_1-4alkoxy; 2) C_2-5alkenylR³, wherein R³ is as defined herein; 3) C_2-5alkynylR³, wherein R³ is as defined herein; and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation; pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

Claims

1. A method of treating breast cancer in a warm-blooded animal in need of such treatment which comprises administering to the animal an effective amount of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof.

2. The method as claimed in claim 1, wherein the warm-blooded animal is a human.

3. A method of treating lung cancer in a warm-blooded animal in need of such treatment which comprises administering to the animal an effective amount of 1 to 50 mg/kg of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof.

4. The method as claimed in claim 3, wherein the warm-blooded animal is a human.

5. A method of treating prostate cancer in a warm-blooded animal in need of such treatment which comprises administering to the animal an effective amount of 1 to 50 mg/kg of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline or a pharmaceutically acceptable salt thereof.

6. The method as claimed in claim 5, wherein the warm-blooded animal is a human.