4-amino-5-cyano-2-anilino-pyrimidine derivatives and their...

C - Chemistry – Metallurgy – 07 – D

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C07D 239/48 (2006.01) A61K 31/505 (2006.01) A61P 35/00 (2006.01) C07D 401/12 (2006.01) C07D 403/12 (2006.01) C07D 405/12 (2006.01) C07D 413/12 (2006.01) C07D 521/00 (2006.01)

Patent

CA 2399864

Compounds of formula (I) wherein: R1 is halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, C1-6alkyl, C2-6alkenyl or C2-6alkynyl; p is 0-4; wherein the values of R1 may be the same or different; R2 is sulphamoyl or a group B-E-; wherein B is optionally substituted as defined within and is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C1-6alkyl, phenyl, a heterocyclic group, phenylC1-6alkyl or (heterocyclic group)C1- 6alkyl; E is C(O)-, N(Ra)C(O)-, -C(O)N(Ra)-, -S(O)r-, -SO2N(Ra)- or -N(Ra)SO2- ; wherein Ra is hydrogen or C1-6alkyl optionally substituted as defined within and r is 1-2; q is 0-2; wherein the values of R2 may be the same or different; and wherein p + q = 1-5; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof are described. Processes for their manufacture and their use as inhibitors of cell cycle kinases, particularly CDK2, CDK4 and/or CDK6 are also described.

L'invention concerne des composés de la formule (I), dans laquelle R?1¿ représente halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyle, mercapto, C¿1-6?alkyle, C¿2-6?alkényle ou C¿2-6?alkynyle; p représente 0-4, les valeurs de R?1¿ pouvant être les mêmes ou différentes, R?2¿ représentant sulphamoyl ou un groupe B-E-, B étant éventuellement substitué comme défini dans le descriptif et sélectionné parmi C¿1-6?alkyle, C¿2-6?alkényle ou C¿2-6?alkynyle, C¿3-8?cycloalkyle, C¿3-8?cycloalkyle, C¿1-6?alkyle, phényle, un groupe hétérocyclique, phényleC¿1-6?alkyle ou (groupe hétérocyclique)C¿1-6?alkyle; E étant -C(O)-, N(R?a¿)C(O)-, -C(O)N(R?a¿)-, -S(O)¿r?-, -SO¿2?N(R?a¿)- ou -N(R?a¿)SO¿2?-; R?a¿ représente hydrogène ou C¿1-6?alkyle éventuellement substitué comme défini dans le descriptif et r représente 1-2; q représente 0-2, les valeurs de R?2¿ pouvant être les mêmes ou différentes et p + q = 1-5; ou un sel pharmaceutiquement acceptable ou un ester de ces composés hydrolysable in vivo. L'invention traite également de procédés de fabrication de ces composés et de leur utilisation comme inhibiteurs de kinases dépendants de cycles cellulaires, en particulier CDK2, CDK4 et/ou CDK6.

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