6331-91-5Relevant articles and documents
Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines
Coxon, Christopher R.,Anscombe, Elizabeth,Harnor, Suzannah J.,Martin, Mathew P.,Carbain, Benoit,Golding, Bernard T.,Hardcastle, Ian R.,Harlow, Lisa K.,Korolchuk, Svitlana,Matheson, Christopher J.,Newell, David R.,Noble, Martin E. M.,Sivaprakasam, Mangaleswaran,Tudhope, Susan J.,Turner, David M.,Wang, Lan Z.,Wedge, Stephen R.,Wong, Christopher,Griffin, Roger J.,Endicott, Jane A.,Cano, Céline
, p. 1746 - 1767 (2017/03/17)
Purines and related heterocycles substituted at C-2 with 4′-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at
Resistance-modifying agents. 8. Inhibition of O6-alkylguanine-DNA alkyltransferase by O6-alkenyl-, O6-cycloalkenyl-, and O6-(2-oxoalkyl)guanines and potentiation of temozolomide cytotoxicity in vitro by O6-(1-cyclopentenylmethyl) guanine
Griffin,Arris,Bleasdale,Boyle,Calvert,Curtin,Dalby,Kanugula,Lembicz,Newell,Pegg,Golding
, p. 4071 - 4083 (2007/10/03)
A series of O6-allyl- and O6-(2-oxoalkyl)guanines were synthesized and evaluated, in comparison with the corresponding O6-alkylguanines; as potential inhibitors of the DNA-repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Simple O6-alkyl- and O6-cycloalkylguanines were weak AGT inactivators compared with O6-allylguanine (IC50 = 8.5 ± 0.6 μM)with IC50 values ranging from 100 to 1000 μM. The introduction of substituents at C-2 of the allyl group of O6-allylguanine reduced activity compared with the parent compound, while analogous compounds in the O6-(2-oxoalkyl)guanine series exhibited very poor activity (150-1000 μM). O6-Cycloalkenylguanines proved to be excellent AGT inactivators, with 1-cyclobutenylmethylguanine (IC50 = 0.55 ± 0.02 μM) and 1-cyclopentenylmethylguanine(IC50 = 0.39 ± 0.04 μM) exhibiting potency approaching that of the benchmark AGT inhibitor O6-benzylguanine (IC50 = 0.18 ± 0.02 μM). 1-Cyclopentenylmethylguanine also inactivated AGT in intact HT29 human colorectal carcinoma cells (IC50 = 0.20 ± 0.07 μM) and potentiated the cytotoxicity of the monomethylating antitumor agent Temozolomide by approximately 3- and 10-fold, respectively, in the HT29 and Colo205 tumor cell lines. The observation that four mutant AGT enzymes resistant to O6-benzylguanine also proved strongly cross-resistant to 1-cyclopentenylmethylguanine indicates that the O6-substituent of each compound makes similar binding interactions within the active site of AGT.
3'-Azido nucleoside compound
-
, (2008/06/13)
The present invention relates to 3'-azido purine nucleosides and their use in medical therapy, particularly for the treatment of human immunodeficiency virus and hepatitis B virus infections, to methods for their preparation and to compositions containing