Bioorganic & medicinal chemistry letters, 2011-02, Vol.21 (4), p.1270-1274
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2011-02, Vol.21 (4), p.1270-1274
- Ort / Verlag
- Amsterdam: Elsevier Ltd
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3- D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs. Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3- D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2010.12.026Titel-ID: cdi_proquest_miscellaneous_907151447
- Format
- –
- Schlagworte
- Analytical, structural and metabolic biochemistry, Binding Sites, Biological and medical sciences, Cell Line, Tumor, chemical reactions, Crystallography, X-Ray, enzyme inhibitors, Enzymes and enzyme inhibitors, Fundamental and applied biological sciences. Psychology, Humans, Hydrogen Bonding, iMHBS, Kinase inhibitor, Medical sciences, Miscellaneous, Models, Chemical, Models, Molecular, mTOR, Pharmacology. Drug treatments, phosphatidylinositol 3-kinase, Phosphatidylinositol 3-Kinases - antagonists & inhibitors, Phosphatidylinositol 3-Kinases - metabolism, PI3K, Protein Kinase Inhibitors - chemical synthesis, Protein Kinase Inhibitors - chemistry, Protein Kinase Inhibitors - pharmacology, protein-serine-threonine kinases, pteridines, pyrimidines, Quinazolines - chemical synthesis, Quinazolines - chemistry, Quinazolines - pharmacology, Structure-Activity Relationship, structure-activity relationships, synthesis, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism, Transferases