title: Novel Pieces for the Emerging Picture of Sulfoximines in Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues of Marketed Drugs and Advanced Clinical Candidates.
abstract: Sulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan-CDK inhibitor), BAY 1143572 (P-TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal-chemistry-relevant properties of sulfoximines. Herein we report the synthesis and in vitro characterization of a variety of sulfoximine analogues of marketed drugs and advanced clinical candidates to gain a better understanding of this neglected functional group and its potential in drug discovery.
authors.affiliation: Drug Discovery, Bayer AG, Müllerstr. 178, 13353, Berlin, Germany.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Sirvent
authors.affiliation: Drug Discovery, Bayer AG, Müllerstr. 178, 13353, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lücking
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D004958:Estradiol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000077267:Fulvestrant; D000068877:Imatinib Mesylate / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000069058:Vardenafil Dihydrochloride / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: C531230:4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide; D000631:Aminopyridines; D010879:Piperazines; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; D013454:Sulfoxides; D000077267:Fulvestrant; D004958:Estradiol; D000069058:Vardenafil Dihydrochloride; D000068877:Imatinib Mesylate; D064007:Ataxia Telangiectasia Mutated Proteins; D018844:Cyclin-Dependent Kinases; C500026:palbociclib; C000589651:ribociclib
keywords: drug design; kinase inhibitors; medicinal chemistry; pharmacophores; sulfoximines