945618-70-2Relevant articles and documents
Synthesis and biological evaluation of 5-substituted O4- alkylpyrimidines as CDK2 inhibitors
Marchetti, Francesco,Cano, Celine,Curtin, Nicola J.,Golding, Bernard T.,Griffin, Roger J.,Haggerty, Karen,Newell, David R.,Parsons, Rachel J.,Payne, Sara L.,Wang, Lan Z.,Hardcastle, Ian R.
supporting information; experimental part, p. 2397 - 2407 (2010/07/09)
CDK2 inhibitory structure-activity relationships have been explored for a range of 5-substituted O4-alkylpyrimidines. Variation of the 5-substituent in the 2,6-diaminopyrimidine series confirmed the 5-nitroso substituent as optimal, and showed that 5-formyl and 5-acetyl substituents were also tolerated at this position. A series of O4-alkyl-N 2-aryl-5-substituted-6-aminopyrimidines revealed interesting structure-activity relationships. In the 5-nitroso series, the optimum O 4-alkyl substituents were cyclohexylmethyl or sec-butyl, combined with a 2-sulfanilyl group. By contrast, in the N2-arylsulfonamido-5- formyl series, the cyclohexylmethyl compound showed relatively poor activity compared with the sec-butyl derivative (22j, (R)-4-(4-amino-6-sec-butoxy-5- formylpyrimidin-2-ylamino)benzenesulfonamide; CDK2 IC50 = 0.8 nM). Similarly, in the N2-arylsulfonamido-5-(hydroxyiminomethyl) series the O4-sec-butyl substituent conferred greater potency than the cyclohexylmethyl (23c, (rac)-4-(4-amino-6-sec-butoxy-5-(hydroxyiminomethyl) pyrimidin-2-ylamino)benzenesulfonamide; CDK2 IC50 = 7.4 nM). The 5-formyl derivatives show selectivity for CDK2 over other CDK family members, and are growth inhibitory in tumour cells (e.g.22j, GI50 = 0.57 μM).
Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2
Sayle, Kerry L.,Bentley, Johanne,Boyle, F. Thomas,Calvert, A. Hilary,Cheng, Yuzhu,Curtin, Nicola J.,Endicott, Jane A.,Golding, Bernard T.,Hardcastle, Ian R.,Jewsbury, Philip,Mesguiche, Veronique,Newell, David R.,Noble, Martin E. M.,Parsons, Rachel J.,Pratt, David J.,Wang, Lan Z.,Griffin, Roger J.
, p. 3079 - 3082 (2007/10/03)
A series of O4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O 6-cyclohexylmethylpurines, 2-
