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Bioorg Med Chem Lett ; 30(6): 126983, 2020 03 15.
Article in English | MEDLINE | ID: mdl-32019711

ABSTRACT

A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.


Subject(s)
Antineoplastic Agents/chemistry , Deoxycytidine/analogs & derivatives , Nitriles/chemistry , Pancreatic Neoplasms/drug therapy , Amides/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Benzylamines/chemistry , Cell Proliferation/drug effects , Deoxycytidine/chemistry , Deoxycytidine/pharmacology , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glycosylation , Humans , Mutation , Phosphoric Acids/chemistry , Proto-Oncogene Proteins p21(ras)/genetics , Purines/chemistry , Structure-Activity Relationship , Gemcitabine
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