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US 8,558,002 B2Granted
Sulfoximines as kinase inhibitors
AssigneeAllergan, Inc.
InventorsSougato Boral, Shimiao Wang, Julie A. Wurster
Life of this patent
Estimating the term…
Abstract
The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
Claims35
A compound represented by the general formula I
- wherein:
- R1 is hydrogen or NH2;
- R2 is hydrogen or NH2;
- X is selected from the group consisting of
- Y is CH or N;
- Ar is an aryl group, wherein said aryl group may be optionally substituted with halogen, alkyl, alkoxy, or alkoxycarbonyl;
- Ar1 is an aryl group, wherein said aryl group may be optionally substituted with halogen, alkyl, alkoxy, alkoxycarbonyl, sulfinyl, thioether, fluoro or chloro-substituted lower alkyl;
- R3 is hydrogen or lower alkyl;
- R4 is hydrogen or lower alkyl;
- n is an integer of from 1 to 6;
- and
- m is an integer of from 1 to 6;
- or a pharmaceutically acceptable salt of said compound.
10 more elements
A compound of selected from the group consisting of
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3-methylbenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}sulfonimidoyl)dipentanoate,
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}sulfonimidoyl)dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[3-(methylthio)benzoyl]amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3-chloro-4-fluorobenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl)sulfonimidoyl)dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[3-(trifluoromethyl)benzoyl]amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3-chlorobenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}sulfonimidoyl)dipentanoate,
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(2-fluoro-5-methylbenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}sulfonimidoyl)dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[3-(methylsulfinyl)benzoyl]amino}lphenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Methyl3-{[(3-{[2-amino-5-({[bis(5-methoxy-5-oxopentyl)(oxido)-λ4-sulfanylidene]amino}carbonyl)pyridin-3-yl]ethynyl}phenyl)amino]carbonyl}benzoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[2-fluoro-5-(trifluoromethyl)benzoyl]amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(3-methoxyphenyl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(3-methylphenyl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(3-chloro-4-methoxyphenyl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(3-chloro-4-fluorophenyl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(5-tert-butylisoxazol-3-yl)amino]carbonyl}phenyl)ethynyl]pyridin-3-yl}carbonyl)sulfonimidoyl]dipentanoate,
- Dimethyl 5,5′-{N-[(6-amino-5-{[3-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)phenyl]ethynyl}pyridin-3-yl)carbonyl]sulfonimidoyl}dipentanoate,
- Dimethyl 5,5′-{N-[(6-amino-5-{[3-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}pyridin-3-yl)carbonyl]sulfonimidoyl}dipentanoate,
- Dimethyl 5,5′-{N-[(6-amino-5-{[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenyl]ethynyl}pyridin-3-yl)carbonyl]sulfonimidoyl}dipentanoate,
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}sulfonimidoyl)diethanoate,
- Dimethyl 5,5′-[N-({6-amino-5-[(3-{[(3-chloro-4-fluorophenyl)amino]carbonyl}phenyl)ethynyl]pyndin-3-yl}carbonyl)sulfonimidoyl]diethanoate, and
- Dimethyl 5,5′-(N-{[6-amino-5-({3-[(3 methylbenzoyl)amino]phenyl}ethynyl) pyndin-3-yl]carbonyl}sulfonimidoyl)diethanoate;
- or a pharmaceutically acceptable salt thereof.
20 more elements
A compound having tyrosine kinase inhibiting activity that is a 2 and/or 6 amino, 5-arylethynyl, 3-carbonyl sulfonimidoyl pyridine, wherein said arylethynyl is substituted with an aryl group.
A method for treating a disease related to unregulated tyrosine kinase signal transduction, where the disease is selected from the group consisting of diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound represented by the general formula I:
- wherein;
- R1 is hydrogen or NH2;
- R2 is hydrogen or NH2;
- X is selected from the group consisting of
- Y is CH or N;
- Ar is an aryl group, wherein said aryl group may be optionally substituted with halogen, alkyl, alkoxy, or alkoxycarbonyl;
- Ar1 is an aryl group, wherein said aryl group may be optionally substituted with halogen, alkyl, alkoxy, alkoxycarbonyl, sulfinyl, thioether, fluoro or chloro-substituted lower alkyl;
- R3 is hydrogen or lower alkyl;
- R4 is hydrogen or lower alkyl;
- n is an integer of from 1 to 6;
- and
- m is an integer of from 1 to 6;
- or a pharmaceutically acceptable salt of said compound.
10 more elements
Dependencies are inferred from the claim text.