Ligands for g-protein coupled receptors

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 453/06 (2006.01) A61K 31/439 (2006.01) A61K 31/55 (2006.01) A61P 43/00 (2006.01) C07D 223/00 (2006.01) C07D 487/08 (2006.01)

Patent

CA 2577964

The invention relates to the generation of a library of compounds enriched in agonist and antagonists for members of the G-protein coupled class of receptors (GPCRs). The library contains compounds of general formula (I) wherein y is any integer from 1 to 8; z is one integer from 0 to 8 with the proviso that y and z cannot simultaneously be 1; X is -CO-(Y)k-(R1)n or SO2- (Y)k-(R1)n; k is 0 or 1; y is a cycloalkyl or polycyloalkyl group (such as an adamantyl, adamantanemethyl, bicyclooctyl, cyclohexyl, cyclopropyl group); or y is a cycloalkenyl or polycycloalkenyl group; each R1 is independently selected from hydrogen or an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, alkylamino, alkylaminoalkyl, alkylaminodialkyl, charged alkylaminotrialkyl or charged alkylcarboxylate radical of 1 to 20 carbon atoms; or each R1 is independently selected from fluoro, chloro, bromo, iodo, hydroxy, oxyalkyl, amino, aminoalkyl, aminodialkyl, charged aminotrialkyl, or carboxylate radical; and n is any integer from 1 to m, where m is the maximum number of substitutions permissible on the cyclo-group Y; or alternatively R1 may be selected from a peptido radical, for example having from 1 to 4 peptidic moieties linked together by peptide bonds (for example a peptido radical of 1 to 4 amino acid residues).

La présente invention concerne la production d'une bibliothèque de composés enrichis en agonistes et antagonistes pour des éléments de la catégorie des récepteurs couplés à la protéine G (GPCRs). La bibliothèque contient des composés de formule générale (I) dans laquelle: y est un entier de 1 à 8; z est un entier de 0 à 8 à la condition que y et z ne valent pas 1 simultanément; X est -CO-(Y)k-(R1)n ou SO2-(Y)k-(R1)n; k vaut 0 ou 1; Y est un groupe cycloalkyle ou polycyloalkyle (tel qu'un groupe adamantyle, adamantaneméthyle, bicyclooctyle, cyclohexyle, cyclopropyle); ou Y est un groupe cycloalcényle ou polycycloalcényle; chaque radical R1 est indépendamment choisi entre hydrogène ou un radical alkyle, haloalkyle, alcoxy, haloalcoxy, alcényle, alcynyle, alkylamino, alkylaminoalkyle, alkylaminodialkyle, alkylaminotrialkyle chargé ou alkylcarboxylate chargé comprenant de 1 à 20 atomes; ou chaque radical R1 est choisi indépendamment entre un radical fluoro, chloro, bromo, iodo, hydroxy, oxyalkyle, amino, aminoalkyle, aminodialkyle, aminotrialkyle chargé, ou carboxylate; et n est un entier de 1 à m, m étant le nombre maximal de substitutions possibles sur le groupe cyclique Y; ou de façon alternative, R1 peut être un radical peptido ayant par exemple de 1 à 4 fractions peptidiques liées par des liaisons peptidiques (par exemple un radical peptido comprenant de 1 à 4 radicaux acide aminé).

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