Substituted arylcycloalkanes, compositions containing them and use thereof
AssigneeAventis Pharma S. A.
InventorsPatrick Mailliet, Marc Capet, Gilles Tiraboschi, Thomas Caulfield
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Abstract
Substituted arylcycloalkanes, compositions containing them and use thereof. The present invention relates especially to substituted arylcycloalkanes with therapeutic activity, which may be used such as in oncology.
Claims14
A product corresponding to formula (I) below:
- 20
- in which:
- A represents a saturated or partially unsaturated, optionally substituted cyclic hydrocarbon containing from 3 to 14 carbon atoms;
- X is selected from the group consisting of O and N—O—(R2),
- each radical R or (R2) is independently selected from the group consisting of H, C1-C7 alkyl, cyclo(C3-C9)alkyl(C1-C7)alkyl, aryl(C1-C7)alkyl-, substituted C1-C7 alkyl, substituted cyclo(C3-C9)alkyl(C1-C7)alkyl- and substituted aryl(C1-C7)alkyl-, or R is a halogen and (R2) is as defined above,
- Ar1 represents a first phenyl nucleus, substituted with 1 to 4 radicals O(R3), in which R3 is independently selected from the group consisting of H and C1-C3 alkyl, and in which an R3 may be simultaneously linked to two adjacent oxygen atoms borne by the first phenyl nucleus,
- Ar2 is selected from the group consisting of 3-hydroxy-4-methoxyphenyl;
- 4-hydroxy-3-methoxyphenyl;
- 3-hydroxy-4-aminophenyl;
- 4-hydroxy-3-aminophenyl;
- 3-hydroxy-4-(N,N-dimethylamino)phenyl;
- 4-hydroxy-3-(N,N-dimethylamino)phenyl.
The product as claimed in any one of the preceding claims, characterized in that R is selected from the group consisting of H, halogen, CH3, CF3, C2H5 and C3-C4 alkyl.
The product as claimed in any one of the preceding claims, characterized in that the first phenyl nucleus Ar1 is substituted with a substituent or a group of substituents chosen from:
- (i) 1 to 4 OCH3 radicals,
- (ii) a methylenedioxy radical,
- (iii) an ethylenedioxy radical,
- (iv) 1 or 2 OCH3 radicals and a methylenedioxy radical,
- (v) 1 or 2 OCH3 radicals and an ethylenedioxy radical.
The product as claimed in any one of the preceding claims, characterized in that it is:
- 1) in racemic form, or
- 2) in a form enriched in one stereoisomer, or
- 3) in a form enriched in one enantiomer;
- and in that it is optionally salified.
A pharmaceutical composition comprising a product as claimed in any one of the preceding claims, in combination with a pharmaceutically acceptable excipient.
A product corresponding to formula (I) below:
- 21
- in which:
- A represents a saturated or partially unsaturated monocycloalkyl or bicycloalkyl radical containing from 3 to 14 carbon atoms, optionally substituted with one or more groups chosen from halogen atoms and C1-C7 alkyl, amino, C1-C7 alkylamino, C1-C7 dialkylamino, hydroxyl, C1-C7 alkoxy, C1-C7 alkylthio, carbonyl, cyano, trifluoromethyl, carboxyl, (C1-C7)alkoxycarbonyl, carboxamido, N—[(C1-C7)alkyl]carboxamido or N,N—[(C1-C7)dialkyl]carboxamido radicals, optionally substituted with a fused C6-C10 aryl group, for example phenyl or naphthyl, or with a fused C2-C13 heteroaryl group, for example 1,2,3-triazolo[c]-, pyrido-, carbazolo- or acridino-;
- X represents an oxygen atom, a radical N—OR′ in which R′ represents a C1-C7 alkyl or aryl(C1-C7)alkyl radical optionally substituted with an amino radical, C1-C7 alkylamino, C1-C7 dialkylamino, hydroxyl, C1-C7 alkoxy, C1-C7 alkylthio, carboxyl, (C1-C7)alkoxycarbonyl, carboxamido, N—[(C1-C7)alkyl]carboxamido or N,N—[(C1-C7)dialkyl]carboxamido;
- R represents a hydrogen or halogen atom, a C1-C7 alkyl or aryl(C1-C7)alkyl-radical optionally substituted with one or more amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkylthio, carboxyl, alkoxycarbonyl, carboxamido, N-alkylcarboxamido or N,N-dialkylcarboxamido radicals;
- Ar1 represents a first phenyl nucleus substituted with 1 to 4 methoxy radicals, or a methylenedioxy radical, or an ethylenedioxy radical, or 1 or 2 methoxy radicals and a methylenedioxy radical, or 1 or 2 methoxy radicals and an ethylenedioxy radical;
- Ar2 represents a 5- to 12-membered nitrogenous heterocycle containing 1 or 2 nitrogen atoms, preferably chosen from 3-pyridyl, 4-pyridyl, 4-pyrimidinyl, 6-quinolyl, 7-quinolyl, 6-isoquinolyl, 7-isoquinolyl, 6-quinazolinyl, 6-quinoxalinyl, N-alkyl-5-indolyl, N-alkyl-6-indolyl, N-alkyl-1,2,3,4-tetrahydro-6-quinolyl, N-alkyl-1,2,3,4-tetrahydro-7-quinolyl, 2-acridinyl, 3-acridinyl, N-alkyl-2-carbazolyl and N-alkyl-3-carbazolyl,
- it being understood that the relative stereochemistry of the groups C(O)Ar1 and Ar2 on the cycloalkyl A is preferably trans.
Dependencies are inferred from the claim text.