Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
First Claim
1. A method for the treatment of vascular reocclusion disorder in a patient suffering from such disorder comprising administering to said patient a pharmaceutically effective amount of a compound of formula ##STR80## wherein ##STR81## is a substituted or unsubstituted monocyclic or bicyclic aryl or heteroaryl ring system of about 5 to about 12 atoms, wherein the monocyclic ring system optionally contains 0 to about 3 hetero atoms and the bicyclic ring system optionally contains 0 to about 4 hetero atoms, wherein the hetero atoms are selected from N, O and S, or optionally the ring of the monocyclic ring system is a saturated carbocyclic optionally containing 0 to about 2 hetero atoms or optionally at least one ring of the bicyclic ring system is a saturated carbocyclic optionally containing 0 to about 4 hetero atoms, wherein the carbocyclic is of about 3 to about 7 atoms, provided that the hetero atoms are not vicinal oxygen or sulfur atoms. and the substituents are described by R and located at any appropriate position of the ring system;
- X is (CHR1)0-4 or (CHR1)m --Z--(CHR1)n ;
Z is O, NR'"'"', S, SO or SO2 ;
m and n are 0 to 3, provided that the sum of m and n is 0 to 3;
R is independently hydrogen, alkyl, alkenyl, phenyl, aralkyl, aralkenyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, aralkoxy, acyloxy, halo, haloalkyl, nitro, amino, monoalkylamino, dialkylamino, acylamino, carboxy, carboxyalkyl, carbalkoxy, carbaralkoxy, carbalkoxyalkyl, carbalkoxyalkenyl, amlnoalkoxy, amido, monoalkylamido, dialkylamido, N,N-cycloalkylamido, phenyl, halophenyl or benzoyl, or two R taken together with the carbon atom to which the two R are attached form keto;
orR1 and R'"'"' are hydrogen or alkyl;
ora pharmaceutically acceptable salt thereof.
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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.
246 Citations
18 Claims
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1. A method for the treatment of vascular reocclusion disorder in a patient suffering from such disorder comprising administering to said patient a pharmaceutically effective amount of a compound of formula ##STR80## wherein ##STR81## is a substituted or unsubstituted monocyclic or bicyclic aryl or heteroaryl ring system of about 5 to about 12 atoms, wherein the monocyclic ring system optionally contains 0 to about 3 hetero atoms and the bicyclic ring system optionally contains 0 to about 4 hetero atoms, wherein the hetero atoms are selected from N, O and S, or optionally the ring of the monocyclic ring system is a saturated carbocyclic optionally containing 0 to about 2 hetero atoms or optionally at least one ring of the bicyclic ring system is a saturated carbocyclic optionally containing 0 to about 4 hetero atoms, wherein the carbocyclic is of about 3 to about 7 atoms, provided that the hetero atoms are not vicinal oxygen or sulfur atoms. and the substituents are described by R and located at any appropriate position of the ring system;
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X is (CHR1)0-4 or (CHR1)m --Z--(CHR1)n ; Z is O, NR'"'"', S, SO or SO2 ; m and n are 0 to 3, provided that the sum of m and n is 0 to 3; R is independently hydrogen, alkyl, alkenyl, phenyl, aralkyl, aralkenyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, aralkoxy, acyloxy, halo, haloalkyl, nitro, amino, monoalkylamino, dialkylamino, acylamino, carboxy, carboxyalkyl, carbalkoxy, carbaralkoxy, carbalkoxyalkyl, carbalkoxyalkenyl, amlnoalkoxy, amido, monoalkylamido, dialkylamido, N,N-cycloalkylamido, phenyl, halophenyl or benzoyl, or two R taken together with the carbon atom to which the two R are attached form keto;
orR1 and R'"'"' are hydrogen or alkyl;
ora pharmaceutically acceptable salt thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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Specification
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- Resources
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Current AssigneeRhone-Poulenc Rorer Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
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Original AssigneeRhone-Poulenc Rorer Pharmaceuticals Incorporated (Sanofi-Aventis U.S., LLC)
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InventorsMaguire, Martin P., Myers, Michael R., Spada, Alfred P., Persons, Paul E.
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Primary Examiner(s)Dees, Jose G.
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Assistant Examiner(s)Cebulak, Mary C.
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Application NumberUS08/439,027Time in Patent Office789 DaysField of Search514/259, 514/340, 514/345, 514/349, 514/312, 514/311, 514/313, 514/314, 514/269, 514/309, 514/307, 514/444, 514/445, 514/447, 514/249, 514/248, 514/252, 514/375US Class Current514/266.24CPC Class CodesA61K 31/517 ortho- or peri-condensed wi...A61K 31/5377 not condensed and containin...C07C 43/2055 containing more than one et...C07C 43/225 containing halogenC07C 43/23 containing hydroxy or O-met...C07D 213/30 Oxygen atomsC07D 213/64 attached in position 2 or 6C07D 215/14 Radicals substituted by oxy...C07D 215/18 Halogen atoms or nitro radi...C07D 215/20 Oxygen atomsC07D 215/233 only one oxygen atom which ...C07D 215/50 attached in position 4C07D 239/74 with only hydrogen atoms, h...C07D 239/88 Oxygen atomsC07D 239/91 with aryl or aralkyl radica...C07D 239/93 Sulfur atomsC07D 239/94 Nitrogen atomsC07D 241/42 with only hydrogen atoms, h...C07D 241/52 Oxygen atomsC07D 265/22 Oxygen atomsView All
