A 13C NMR approach to categorizing potential limitations of alpha,beta-unsaturated carbonyl systems in drug-like molecules.
Compounds that contain an alpha,beta-unsaturated carbonyl moiety are often flagged as potential Michael acceptors. All alpha,beta-unsaturated carbonyl moieties are not equivalent, however, and we sought to better understand this system and its potential implications in drug-like molecules. Measurement of the (13)C NMR shift of the beta-carbon and correlation to in vitro results allowed compounds in our collection to be categorized as potential Michael acceptors, potential substrates for NADPH, or as photoisomerizable.
Cusack
Kevin P
KP
Abbott Bioresearch Center, 381 Plantation Street, Worcester, MA 01605, USA. kevin.cusack@abbott.com
Arnold
Lee D
LD
Barberis
Claude E
CE
Chen
Haipeng
H
Ericsson
Anna M
AM
Gaza-Bulseco
Georgeen S
GS
Gordon
Thomas D
TD
Grinnell
Christine M
CM
Harsch
Andreas
A
Pellegrini
Maria
M
Tarcsa
Edit
E
D002247:Carbon Isotopes / Q000737:chemistry; D015195:Drug Design; D005030:Ethylenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D010777:Photochemistry; D013329:Structure-Activity Relationship
D002247:Carbon Isotopes; D005030:Ethylenes; D007659:Ketones