title: Nonracemic synthesis of GK-GKRP disruptor AMG-3969.
abstract: A nonracemic synthesis of the glucokinase-glucokinase regulatory protein disruptor AMG-3969 (5) is reported. Key features of the synthetic approach are an asymmetric synthesis of the 2-alkynyl piperazine core via a base-promoted isomerization and a revised approach to the synthesis of the aminopyridinesulfonamide with an improved safety profile.
authors.affiliation: Therapeutic Discovery, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Bourbeau
authors.forename: Kate S
authors.initials: KS
authors.lastname: Ashton
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: David J
authors.initials: DJ
authors.lastname: St Jean
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D007536:Isomerism; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C000592677:1-benzyl-3-(1-propyn-1-yl)piperazine; C000592678:1-benzyl-3-(2-propyn-1-yl)-2,5-piperazinedione; C585748:2-(4-(4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol; D001593:Benzyl Compounds; D002219:Carbamates; D002352:Carrier Proteins; D007202:Indicators and Reagents; D010879:Piperazines; D011725:Pyridines; D013449:Sulfonamides; C080906:glucokinase regulatory protein; C000592680:tert-butyl(5-(chlorosulfonyl)-2-pyridinyl)carbamate