Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy.
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.
Jansma
Ariane
A
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Zhang
Qiong
Q
Li
Bing
B
Ding
Qiang
Q
Uno
Tetsuo
T
Bursulaya
Badry
B
Liu
Yi
Y
Furet
Pascal
P
Gray
Nathanael S
NS
Geierstanger
Bernhard H
BH
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
C473352:PD 166326; D011725:Pyridines; D011728:Pyridones; D011743:Pyrimidines; D014867:Water; C410732:PD 180970; D004121:Dimethyl Sulfoxide