title: Sulfoximine substituted quinazolines for pharmaceutical compositions US 20150005278 (A1): a patent evaluation.
abstract: Mnk1 and Mnk2 are protein kinases responsible for phosphorylating eIF4E, a eukaryotic initiation factor responsible for initiating translation. Inhibiting Mnk1 and Mnk2 could therefore play a role in treating metabolic diseases such as cancer, diabetes, and hyperlipidemia. A wide range of sulfoximine substituted quinazolines were synthesised and evaluated for their Mnk1 and Mnk2 inhibitory activity. Amongst these compounds, 26 quinazolines showed activity against Mnk1 at <100 nM and 54 showed activity against Mnk2 at 1 nM. The results indicate that this scaffold is much more active against Mnk2 than Mnk1. The synthesised compounds may be future drugs in the treatment of metabolic diseases.
authors.affiliation: a School of Chemistry , University of KwaZulu-Natal , Durban , South Africa.
authors.forename: Kaalin
authors.initials: K
authors.lastname: Gopaul
authors.affiliation: a School of Chemistry , University of KwaZulu-Natal , Durban , South Africa.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Koorbanally
mesh_terms: D015195:Drug Design; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008659:Metabolic Diseases / Q000188:drug therapy / Q000503:physiopathology; D010330:Patents as Topic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013457:Sulfur Compounds / Q000737:chemistry
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; D011799:Quinazolines; D013457:Sulfur Compounds; C491395:MKNK1 protein, human; C486342:MKNK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Mnk inhibitors; Mnk1; Mnk2; quinazoline; sulfoximine