US 5,773,459 AGranted

Urea- and thiourea-type compounds

AssigneeSugen, Inc.

InventorsPeng Cho Tang, Gerald McMahon

Life of this patent

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Abstract

The present invention relates to molecules capable of modulating tyrosine signal transduction to prevent and treat cell proliferative disorders or cell differentiation disorders associated with particular tyrosine kinases by inhibiting one or more abnormal tyrosine kinase activities.

Claims18

Dependent claims

A method for treating a cell proliferative or cell differentiation disorder by inhibiting a tyrosine kinase associated with said disorder, wherein said disorder is selected from the group consisting of a cancer, restenosis, retinopathy, psoriasis, hyperimmune response, hepatic cirrhosis, a mesangial cell proliferative disorder, a HER2 disorder, an EGFR disorder, an IGFR disorder, a PDGFR disorder, a met disorder, a Src disorder, and a KDR/Flk-1 disorder, comprising the step of administering a therapeutically effective amount of a compound of the formula ##STR3## or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein;

X is oxygen or sulfur
R.sub.1 is selected from the group consisting of optionally substituted aryl, alkylaryl, and heteroaryl and
R.sub.2-6 are independently selected rom the group consisting of hydroxy, hydrogen, alkyl, alkoxy, cyano, nitro, halo trihalomethyl, amide, carboxamide, sulfonyl, and sulfoxamide.

A compound selected from the group consisting of

N-3-Chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-(4-t-butylphenyl)urea,
N-3-Chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-(3,5-di-trifluoromethylphen yl)urea,
N-2-(2,4-Dichlorophenoxy)pyrid-5-yl!-N'-4-trifluoromethylmercapto)phenyl! urea,
N-(4-Cyanophenyl)-N'-4-(piperid-1-yl)sulfonyl!phenyl!thiourea,
N-(4-t-Butylphenyl)-N'-3-chloro-4-(isopropylsulfonyl)thien-2-yl!urea,
N-3-chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-(4-trifluoromethylphenyl)ur ea,
N-3-Chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-4-trifluoromethylphenyl)thi ourea,
N-3-Chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-4-(piperid-1-yl)sulfonylph enyl!thiourea,
N-3-Chloro-4-(isopropylsulfonyl)thien-2-yl!-N'-4-phenylaminosulfonylpheny l!thiourea,
N-4-(4-Chlorophenylsulfonyl)thien-3-yl!-N'-4-(piperid-1-yl)sulfonylphenyl !thiourea,
N-4-(4-Chlorophenylsulfonyl)thien-3-yl}-N'-(4-trifluoromethylphenyl)thiour ea,
N-(5-Nitrothiazol-2-yl)-N'-(4-trifluoromethylphenyl)urea,
N- (5-Nitrothiazol-2-yl)-N'-(4-trifluoromethylphenyl)thiourea,
N-(5-Nitrothiazol-2-yl)-N'-4-(phenylaminosulfonyl)phenyl!thiourea,
N-(4-t-Butylphenyl)-N'-(3-ethoxycarbonyl-4-methylthien-2-yl)urea,
N-(3-Ethoxycarbonyl-4-methylthien-2-yl)-N'-(4-trifluoromethylphenyl)thioure a,
N-(3-Ethoxycarbonyl-4-methylthien-2-yl)-N'-4-(piperid-1-yl)sulfonyl!pheny l!thiourea,
N-(4-t-Butylphenyl)-N'-(2,4-dinitrothien-5-yl)urea,
N-(4-t-Butylphenyl)-N'-(3-cyano-5-methoxycarbonyl-4-methylthien-2-yl)urea,
N-(3-Cyano-5-methoxycarbonyl-4-methylthien-2-yl)-N'-(4-trifluoromethylpheny l)urea,
N-(3-Cyano-5-methoxycarbonyl-4-methylthien-2-yl)N'-4-(phenylaminosulfonyl) phenyl!thiourea,
N-(3-Methylthien-2-yl)-N'-(4-trifluoromethylphenyl)thiourea,
N-(3-Methylthien-2-yl)-N'-4-(piperid-1-yl)sulfonyl!phenyl!thiourea,
N-(4-t-Butylphenyl)-N'-4-(4-chlorophenyl)-3-cyanopyrrol-2-yl!urea,
N-4-(4-Chlorophenyl)-3-cyanotpyrrol-2-yl!-N'-(4-trifluoromethylphenyl)urea
N-4-(4-Chlorophenyl)-3-cyanopyrrol-2-yl!-N'-4-(piperid-1-yl)sulfonyl!phe nyl!thiourea,
N-(4-t-Butylphenyl)-N'-4-(isopropylsulfonyl)thien-2-yl!urea,
N-4-(Isopropylsulfonyl)thien-2-yl!-N'-4-trifluoromethylphenyl!thiourea,
N-4-(Isopropylsulfonyl)thien-2-yl!-N'-4-(piperid-1-yl)sulfonyl!phenyl!th iourea,
N-(4-t-Butylphenyl)-N'-4-4-(trifluoromethyl)phenylaminosulfonyl!thien-2-y l!urea,
N-4-(Piperid-1-yl)sulfonyl!phenyl!-N'-4-4-(trifluoromethyl)phenylaminos ulfonyl!thien-2-yl!thiourea,
N-(3-Aminocarbonyl-4-methylthien-2-yl)-N'-(4-trifluoromethylphenyl)thiourea
N-4-(Piperid-1-yl)sulfonyl!phenyl!-N'-4-trifluoromethylphenyl)thiourea,
N-4-(Piperid-1-yl)sulfonyl!phenyl!-N'-4-(4-trifluoromethylbenzyl!thioure a,
N-2-(2,4-dichlorophenoxy)pyrid-5-yl!-N'-(4-trifluoromethylphenyl)thiourea.

32 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/486,816Filed 7 Jun 1995
Granted: 30 Jun 1998
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…
C07D 277/58
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 295/26
With hetero atoms directly attached to ring nitrogen atoms: sulfur atoms

Family

No related US applications are recorded in the indexed filing history.

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Abstract

Facts

Application

08/486,816Filed 7 Jun 1995

Granted

30 Jun 1998

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 213/75
Nitrogen atoms: amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…
C07D 277/58
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 295/26
With hetero atoms directly attached to ring nitrogen atoms: sulfur atoms