US 2004/0204458 A1 · Use of Lck inhibitors for treatment of immunologic diseases

Abstract

The invention relates to a method of treating immunologic diseases or pathological conditions involving an immunologic component using certain Lck inhibitors already known as kinase inhibitors for therapy in oncology, optionally in combination with one or more other drugs selected from NSAIDs, steroids, DMARDs, immunsuppressives, biologic response modifiers and antinfectives, pharmaceutical compositions comprising said Lck inhibitors together with said other drugs, and the use of the Lck inhibitors for the manufacture of a pharmaceutical composition for the treatment of immunologic diseases or pathological conditions involving an immunologic component.

A method for treating immunologic diseases or pathological conditions involving an immunologic component comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition comprising a compound selected from

(A) (Z)-3-(1-(4-(piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(methylsulfonylamino)-2-indolinone;
(B) (Z)-3-(1-(4-(piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(ethylsulfonylamino)-2-indolinone;
(C) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylene)-5-(ethylsulfonylamino)-2-indolinone;
(D) (Z)-3-(1-(4-(piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(phenylsulfonylamino)-2-indolinone;
(E) (Z)-3-(1-(4-(piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(4-amino-phenylsulfonylamino)-2-indolinone;
(F) (Z)-3-(1-(4-(pyrrolidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(ethylsulfonylamino)-2-indolinone;
(G) (Z)-3-(1-(4-(4-(3-aminopropyl-piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(ethylsulfonylamino)-2-indolinone;
(H) (Z)-3-(1-(4-(N-(piperidin-1-yl-methylcarbonyl)-N-methyl-amino)-phenylamino)-1-phenyl-methylene)-5-(phenylsulfonylamino)-2-indolinone;
(I) (Z)-3-(1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulfonyl-amino)-phenyl-amino)-1-phenyl-methylene)-5-(N-methyl-N-phenylsulfonyl-amino)-2-indolinone;
(J) (Z)-3-(1-(4-(N-methyl-N-(piperidin-1-yl-methylcarbonyl)-amino)-phenylamino)-1-phenyl-methylene)-5-(N-methyl-N-phenylsulfonyl-amino)-2-indolinone;
(K) (Z)-3-(1-(2-benzimidazolyl-amino)-1-phenyl-methylene)-5-amido-2-indolinone;
(L) (Z)-3-(1-(4-(N-methyl-propionylamino)-phenylamino)-1-phenyl-methylene)-5-amido-2-indolinone;
(M) (Z)-3-(1-(4-(N-(2-dimethylamino-ethyl )-N-methylsulfonyl-amino)-phenyl-amino)-1-phenyl-methylene)-2-indolinone;
(N) (Z)-3-(1-(4-(N-(3-dimethylaminopropyl)-N-propionyl-amino)-phenylamino)-1-phenyl-methylene)-2-indolinone;
(O) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylene)-5-(butylcarbamoyl)-2-indolinone;
(P) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(naphth-1-yl-methyl-carbamoyl)-2-indolinone;
(Q) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylene)-5-(N-butyl-N-phenyl-carbamoyl)-2-indolinone;
(R) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(hexylcarbamoyl)-2-indolinone;
(S) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(cyclohexylmethyl-carbamoyl)-2-indolinone;
(T) (Z)-3-(1-(4-(N-methylsulfonyl-N-(2-dimethylamino-ethyl)-amino)-phenylamino)-1-phenyl-methylen)-5-(cyclohexylmethyl-carbamoyl )-2-indolinone;
(U) (Z)-3-(1-(4-(butylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(cyclo-hexylmethyl-carbamoyl)-2-indolinone;
(V) (Z)-3-(1-(4-(pyrrolidin-1-yl-methyl)-phenylamino)-1-phenyl-methylen )-5-cyclohexylmethyl-carbamoyl)-2-indolinone;
(W) (Z)-3-(1-(4-(diethylaminomethyl )-phenylamino)-1-phenyl-methylen)-5-(cyclo-hexylmethyl-carbamoyl)-2-indolinone;
(X) (Z)-3-(1-(4-(diethylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(N-(3-chlorobenzyl)-carbamoyl)-2-indolinone;
(Y) (Z)-3-(1-(4-(diethanolaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(butylcarbamoyl)-2-indolinone;
(Z) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(N-(3-chlorobenzyl )-carbamoyl)-2-indolinone;
(AA) (Z)-3-(1-(4-(N-acetyl-N-(2-dimethylamino-ethyl)-amino)-phenylamino)-1-phenyl-methylen )-5-(N-(3-chlorobenzyl)-carbamoyl)-2-indolinone;
(AB) (Z)-3-(1-(4-(butylaminomethyl)-phenylamino)-1-phenyl-methylen)-5-(N-(3-chlorobenzyl)-carbamoyl)-2-indolinone;
(AC) (Z)-3-(1-(4-(piperidin-1-yl-methyl)-phenylamino)-1-phenyl-methylene)-5-(N-methyl-N-phenyl-aminosulfonyl)-2-indolinone;
(AD) (Z)-3-(1-(4-(piperidin-1-yl-methyl )-phenylamino)-1-phenyl-methylene)-5-(N-butyl-N-methyl-aminosulfonyl)-2-indolinone;
(AE) (Z)-3-(1-(4-(dimethylaminomethyl)-phenylamino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AF) (Z)-3-(1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-phenylamino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AG) (Z)-3-(1-(4-(ethylaminomethyl)-phenylamino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AH) (Z)-3-(1-(4-(1-methyl-imidazol-2-yl)-phenylamino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AI) (Z)-3-(1-(4-(N-(dimethylaminomethylcarbonyl)-N-methyl-amino)-phenylamino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AJ) (Z)-3-(1-(4-(methylaminomethyl)-anilino)-1-phenyl-methylene)-6-methoxycarbonyl-2-indolinone;
(AK) (Z)-3-(1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-phenylamino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone;
and
(AL) 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)-quinazoline
the tautomers, the stereoisomers and the physiologically acceptable salts thereof, or a combination of any of the above.

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Use of Lck inhibitors for treatment of immunologic diseases

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Use of Lck inhibitors for treatment of immunologic diseases

Life of this patent

Abstract

Claims20