title: Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy.
abstract: 2D 1H-15N HMBC NMR acquired at natural abundance and DMSO titration monitored by 1D 1H NMR verified the existence of an intramolecular hydrogen bond that was designed to mimic the pyrimidinone ring of a class of kinase inhibitors. A scalar coupling across the hydrogen bond was detected in organic and aqueous solvent, suggesting a simple and general approach for testing the propensity of intramolecular hydrogen bonds to stabilize pseudo-rings in drug scaffolds.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Ariane
authors.initials: A
authors.lastname: Jansma
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Uno
authors.forename: Badry
authors.initials: B
authors.lastname: Bursulaya
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Gray
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Geierstanger
mesh_terms: D004121:Dimethyl Sulfoxide; D015195:Drug Design; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011725:Pyridines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D012995:Solubility; D014867:Water
chemical_list: C473352:PD 166326; D011725:Pyridines; D011728:Pyridones; D011743:Pyrimidines; D014867:Water; C410732:PD 180970; D004121:Dimethyl Sulfoxide