Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase

• US 5,714,493 A
• Filed: 06/04/1996
• Issued: 02/03/1998
• Est. Priority Date: 05/10/1991
• Status: Expired

• Current Assignee: Aventis Pharmaceuticals Incorporated (Sanofi )
• Original Assignee: Rhone-Poulenc Rorer Pharmaceuticals Incorporated (Sanofi )
• Inventors: Maguire, Martin P., Myers, Michael R., Spada, Alfred P., Persons, Paul E., Zilberstein, Asher, Hsu, Chin-Yi Jenny, Johnson, Susan E.
• Primary Examiner(s): Dees, Jose G.
• Assistant Examiner(s): Cebuilak, Mary C.
• Application Number:
  US08/652,444
• Time in Patent Office: 609 Days
• Field of Search: 514/259, 514/248, 514/249, 514/252, 514/253, 514/254, 514/230.5
• US Class Current: 514/262.1
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: C07C 43/2055 containing more than one ether bond
• CPC Class Codes: C07C 43/225 containing halogen
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 215/14 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 215/18 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 215/20 Oxygen atoms
• CPC Class Codes: C07D 215/233 only one oxygen atom which is attached in position 4
• CPC Class Codes: C07D 215/50 attached in position 4
• CPC Class Codes: C07D 239/74 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
• CPC Class Codes: C07D 239/88 Oxygen atoms
• CPC Class Codes: C07D 239/91 with aryl or aralkyl radicals attached in position 2 or 3
• CPC Class Codes: C07D 239/93 Sulfur atoms
• CPC Class Codes: C07D 239/94 Nitrogen atoms
• CPC Class Codes: C07D 241/42 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 241/52 Oxygen atoms
• CPC Class Codes: C07D 265/22 Oxygen atoms
• CPC Class Codes: C07D 277/64 : with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

This invention relates to the treatment of intimation in a patient suffering from such disorder. More specifically, the invention relates to mono- and/or bicyclic aryl or heteroaryl quinazoline compounds in the treatment of inflammation.

Claims

1. A method for the treatment of inflammation in a patient suffering from such disorder comprising administering to said patient an effective amount of the compound of formula:

##STR24## wherein Ar is a substituted or unsubstituted benzene, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1,2,4-triazole, pyridine, 2(1H)-pyridone, 4(1H)-pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2,3-dihydroindole, 1H-indazole, indoline, benzopyrazole, 1,3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido 2,3-b!pyrazine, pyrido 3,4-b!pyrazine, pyrido 3,2-c!pyridazine, pyrido 3,4-b!-pyridine, 1 H- pyrazole 3,4-d!pyrimidine, pteridine, 2(1H)-quinolone, 1(2H)-isoquinolone, 1,4-benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phthalazine, or cinnoline;

X is a bond, O, S, SO, SO₂, OCH₂, C═

C, C.tbd.C, C═

S, SCH₂, NH, NHCH₂, NR₄ or NR₄ CH₂ ;

R is independently, located at any appropriate position of Ar, hydrogen, alkyl, alkenyl, phenyl, aralkyl, aralkenyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, aralkoxy, aryloxy, acyloxy, halo, haloalkyl, nitro, cyano, amino, mono- and di-alkylamino, acylamino, carboxy, carboxyalkyl, carbalkoxy, carbaralkoxy, carbalkoxyalkyl, carbalkoxyalkenyl, aminoalkoxy, amido, mono-alkylamido, di-alkylamido, N, N-cycloalkylamido, sulfonyl, mono-alkyl sulfonyl, di-alkyl sulfonyl, sulfamoyl, mono-alkyl sulfamoyl, di-alkyl sulfamoyl, halophenyl or benzoyl;

R₄ is alkyl or benzyl;

R₅ is hydrogen, alkyl, alkylthio, cycloalkyl, hydroxy, alkoxy, aralkoxy, aryl, halo, haloalkyl, carboxy or carbalkoxy; and

R₆ and R₇ are alkoxy or aralkoxy;

or

a pharmaceutically acceptable salt thereof,

provided that;

when R₅ is hydrogen, R₆ and R₇ are methoxy, and X is a bond, then Ar is other than R substituted phenyl wherein R is hydrogen or (mono- or di-)methoxy;

or when R₅ is hydrogen, R₆ and R₇ are alkoxy, X is NHCH₂ or NR₄, and R₄ is hydrogen, then Ar is other than R substituted Ar is phenyl wherein R is hydrogen;

or when R₅ is hydrogen or methoxy, R₆ and R₇ are methoxy, and X is NHCH₂, then Ar is other than R substituted pyridinyl wherein R is hydrogen, mono-alkyl or mono-hydroxy, or Ar is other than R substituted indol-3-yl wherein R is hydrogen.