Substituted oxindole derivatives as protein tyrosine kinase...

Details Substituted oxindole derivatives as protein tyrosine kinase... Substituted oxindole derivatives as protein tyrosine kinase...

C - Chemistry, Metallurgy

07

D

C07D 209/40 (2006.01) A61K 31/40 (2006.01) C07D 209/34 (2006.01) C07D 401/06 (2006.01) C07D 401/12 (2006.01) C07D 403/04 (2006.01) C07D 403/12 (2006.01) C07D 405/12 (2006.01) C07D 413/04 (2006.01) C07D 471/04 (2006.01) C07D 487/04 (2006.01) C07D 491/04 (2006.01) C07D 498/04 (2006.01) C07D 513/04 (2006.01) C07D 521/00 (2006.01)

Patent

CA 2302572

Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7- sulfonyl -C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1- 12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di- C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3- Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het- amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

L'invention concerne des composés représentés par la formule (I).X y est N, CH, CCF¿3?, ou C(C¿1-12? aliphatique); R?4¿ est acide sulfonique, C¿1-12? aliphatique sulfonyle, sulphonyle C¿1-12? aliphatique, C¿1-12? aliphatique sulfonyle-C¿1-16?, aliphatique, C¿1-16? aliphatique-amino, R?7¿-sulfonyle, R?7¿-sulfonyle -C¿1-12? aliphatique, R?7¿-aminosulfonyle, R?7¿-aminosulfonyle-C¿1-12?, aliphatique, R?7¿-sulfonylamino, R?7¿-sulfonylamino-C¿1-12? aliphatique, aminosulfonylamino, di-C¿1-12? aliphatique amino, di-C¿1-12? aliphatique aminocarbonyle, di-C¿1-12? aliphatique aminosulfonyle, di-C¿1-12? aliphatique amino, di-C¿1-12? aliphatique aminocarbonyle, di-C¿1-12? aliphatique aminosulfonyle¿ ?C¿1-12? aliphatique, (R?8¿)¿1-13?-arylamino, (R?8¿)¿1-13?-arylsulfonyle, (R?8¿)¿1-13?-arylaminosulfonyle, (R?8¿)¿1-13?-arylsulfonylamino, het-amino, het-sulfonyle, het-aminosulfonyle, aminoiminoamino ou aminoiminoaminosulfonyle; R?5¿ est hydrogène; en outre, R?4¿ et R?5¿ sont éventuellement réunis afin de former un cycle. L'invention concerne également des formulations pharmaceutiques qui renferment ces dérivés et leur utilisation thérapeutique, en particulier dans le traitement de maladies à médiation CDK2, telles que l'alopécie provoquée par la chimiothérapie ou la radiothérapie anticancéreuses.

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