Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase

• US 5,656,643 A
• Filed: 02/08/1995
• Issued: 08/12/1997
• Est. Priority Date: 11/08/1993
• Status: Expired due to Term

• Current Assignee: Rhone-Poulenc Rorer Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Original Assignee: Rhone-Poulenc Rorer Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
• Inventors: Maguire, Martin P., Myers, Michael R., Spada, Alfred P., Persons, Paul E.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US08/385,258
• Time in Patent Office: 916 Days
• Field of Search: 514/314, 514/312, 514/313, 546/157, 546/159, 546/167
• US Class Current: 514/312
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 215/20 Oxygen atoms
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond

Abstract

This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.

Claims

1. A method of inhibiting cell proliferation in a patient suffering from a disorder characterized by such cell proliferation comprising administering to the patient a pharmaceutically effective amount of a PDGF receptor inhibiting compound of formula:

##STR48## wherein X is (CHR₁)_0-4 or (CHR₁)_m --Z--(CHR₁)_n ;

Z is O, NR'"'"', S, SO or SO₂ ;

m and n are 0-3 and m+n=0-3;

R substitution besides hydrogen independently includes alkyl, alkenyl, phenyl, aralkyl, aralkenyl, hydroxy, alkoxy, aralkoxy, acyloxy, halo, haloalkyl, amino, monoalkylamino, dialkylamino, acylamino, carboxy, carbalkoxy, carbaralkoxy, carbalkoxyalkyl, carbalkoxyalkenyl, am ido, monoalkylamido, dialkylamido and N,N-cycloalkylamido; and

R₁ and R'"'"' are hydrogen or alkyl,

or a pharmaceutically acceptable salt thereof, to which the cell proliferation is sensitive to said compound above.

2. The method according to claim 1, where said compound is 3-(2-methoxypyrid-5-yl)-6,7-dimethoxyquinoline or a pharmaceutically acceptable salt thereof.

3. 3-(2-methoxypyrid-5-yl)-6,7-dimethoxyquinoline or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 3, and a pharmaceutically acceptable carrier.