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US 7,491,710 B2Granted
Organophosphorus derivatives of indazoles and use thereof as medicinal products
AssigneeAventis Pharma S.A.
InventorsMarie-Pierre Cherrier, Francois Clerc, Alain Commercon, Patrick Mailliet, Hervé Minoux, Bruno Filoche-Rommé
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Abstract
The present invention relates in particular to novel chemical compounds, particularly to novel organophosphorus derivatives of indazoles, to the compositions containing them, and to the use thereof as medicinal products for treating cancers.
Claims19
A compound of formula (I) below:
- wherein
- W is a covalent bond or O;
- X is a covalent bond or a group chosen from —C═O—NRa—, NRa—C═O, —(CH2)n—, —CH═CH—, —C≡C—, —NRa—, S, O, —SO2—, —SO, —CO or —COO, wherein Ra is H or (C1-C4)alkyl which optionally forms a ring with R1, and wherein n is an integer from 0 to 12;
- R1 is H, alkyl, cycloalkyl, aryl or heteroaryl;
- said alkyl, cycloalkyl, aryl or heteroaryl is optionally substituted;
- R and R2 may be identical or different and are independently of each other selected from H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyl, alkoxy and aryloxy radicals, all of which except H are optionally substituted;
- Y is a covalent bond or a radical chosen from:
- —C═O—NRa—, —C═O—O—, —C═O—, —(CH2)n— or —SO2—, wherein Ra is H or (C1-C4)alkyl which optionally forms a ring with R3 and n is as defined above;
- R3 is selected from the group consisting of H, alkyl, cycloalkyl, aryl, and heteroaryl;
- all of which except H are optionally substituted;
- R4, R6 and R7, which may be identical or different, are independently chosen from H, halogen, (C1-C4)alkyl, (C1-C4)alkoxy, cyano, —N(Rb)Rc, —C═O—N(Rb)Rc and —N(Rb)—CO—Rc, wherein Rb and Rc are independently chosen from H, (C1-C4)alkyl and (C3-C6)cycloalkyl;
- or an enantiomer, a stereoisomer, a rotomer or a tautomer thereof, or a mixture in any combination thereof, a solvate thereof or a pharmaceutically acceptable salt thereof;
- with the proviso that
- when X=—SO2— or —SO—, R1 is not H;
- when Y is —C═O—O—, or —SO2—, R3 is not H;
- and
- with the exception of the products below
14 more elements
A pharmaceutical composition comprising a compound of formula (I) below:
- wherein
- W is a covalent bond or O;
- X is a covalent bond or a group chosen from —C═O—NRa—, NRa—C═O, —(CH2)n—, —CH═CH—, —C≡C—, —NRa—, S, O, —SO2—, —SO, —CO or —COO, wherein Ra is H or (C1-C4)alkyl which optionally forms a ring with R1, and wherein n is an integer from 0 to 12;
- R1 is H, alkyl, cycloalkyl, aryl or heteroaryl;
- said alkyl, cycloalkyl, aryl or heteroaryl is optionally substituted;
- R and R2 may be identical or different and are independently of each other selected from H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxyl, alkoxy and aryloxy radicals, all of which except H are optionally substituted;
- Y is a covalent bond or a radical chosen from:
- —C═O—NRa—, —C═O—O—, —C═O—, —(CH2)n— or —SO2—, wherein Ra is H or (C1-C4)alkyl which optionally forms a ring with R3 and n is as defined above;
- R3 is selected from the group consisting of H, alkyl, cycloalkyl, aryl, and heteroaryl;
- all of which except H are optionally substituted;
- R4, R6 and R7, which may be identical or different, are independently chosen from H, halogen, (C1-C4)alkyl, (C1-C4)alkoxy, cyano, —N(Rb)Rc, —C═O—N(Rb)Rc and —N(Rb)—CO—Rc, wherein Rb and Rc are independently chosen from H, (C1-C4)alkyl and (C3-C6)cycloalkyl;
- or an enantiomer, a stereoisomer, a rotomer or a tautomer thereof, or a mixture in any combination thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers, diluents or excipients.
9 more elements
A compound selected from the group consisting of:
- methylphenylphosphinic acid 3-((E)-styryl)-1H-indazol-5-yl ester;
- diphenylphosphinic acid 3-((E)-styryl)-1H-indazol-5-yl ester;
- methylphenylphosphinic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester;
- diphenylphosphinic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester;
- methylphenylphosphinic acid 3-[5-(2-morpholin-4-ylethoxy)-1H-indol-2-yl]-1H-indazol-5yl ester;
- phenylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester methyl ester;
- phenylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester isopropyl ester;
- phenylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester benzyl ester;
- methylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester methyl ester;
- phenylphosphonic acid methyl ester 3-(1H-ptrrol-2-yl)-1H-indazol-5-yl ester;
- [3-((E)-styryl)-1H-indazol-5-yl]phosphonic acid dimethyl ester;
- [3-((E)-styryl)-1H-indazol-5-yl]phosphonic acid monomethyl ester;
- [3-((E)-styryl)-1H-indazol-5-yl]phosphonic acid diethyl ester;
- [3-(1H-indol-2-yl)-1H-indazol-5-yl]phosphonic acid monomethyl ester;
- (3-thiophen-2-yl-1H-indazol-5-yl)phosphonic acid monomethyl ester;
- [3-(1H-pyrrol-2-yl)-1H-indazol-5-yl]phosphonic acid monomethyl ester;
- dimethylphosphinic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester;
- methyl-phosphonic acid methyl ester 3-[5-(2-piperidin-1-yl-ethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester;
- methylphosphonic acid mono-{3-[5-(2-piperazin-1-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-yl} ester;
- methylphosphonic acid mono-{3-[5-(2-diethylaminoethoxy)-1H-indol-2-yl]-1H-indazol-5-yl} ester;
- methyl-phosphonic acid 3-[5-(2-diethylaminoethoxy)-1H-indol-2-yl]-1H-indazol-5yl ester methyl ester;
- phenylphosphonic acid ethyl ester 3-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-indazol-5-yl ester;
- phenylphosphonic acid 3-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-indazol-5-yl ester methyl ester;
- phenylphosphonic acid methyl ester 3-styryl-1H-indazol-5-yl ester;
- phenylphosphonic acid 3-thiophen-2-yl-1H-indazol-5-yl ester methyl ester;
- phenylphosphonic acid 3-benzo[b]thiophen-2-yl-1H-indazol-5-yl ester methyl ester;
- methylphosphonic acid methyl ester 3-[5-(2-morpholin-4-ylethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester;
- methylphosphonic acid 3-[6-(2-diethylamino-ethoxy)-1H-indol-2-yl]-1H-indazol-5-yl ester methyl ester;
- ethylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester methyl ester;
- methylphosphonothioic acid O-[3-(1H-indol-2-yl)-1H-indazol-5-yl] ester O-methyl ester;
- cyclohexylphosphonic acid 3-(1H-indol-2-yl)-1H-indazol-5-yl ester methyl ester;
- and
- phenylphosphonic acid mono-[3-(1H-indol-2-yl)-1H-indazol-5-yl] ester;
- or a pharmaceutically salt thereof.
31 more elements
Dependencies are inferred from the claim text.