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.
Abbott Bioresearch Center, 381 Plantation Street, Worcester, MA 01605, USA. kevin.cusack@abbott.com
Kevin P
KP
Cusack
Lee D
LD
Arnold
Claude E
CE
Barberis
Haipeng
H
Chen
Anna M
AM
Ericsson
Georgeen S
GS
Gaza-Bulseco
Thomas D
TD
Gordon
Christine M
CM
Grinnell
Andreas
A
Harsch
Maria
M
Pellegrini
Edit
E
Tarcsa
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