Intramolecular C-H--O interaction between lactam oxygen and N-alkyl protons.
We report evidence of an unusual C-H--O interaction between an alpha-methylene hydrogen of the alkylamine chain of substituted (N,N-dimethylamino)propyl-azetidinones, substituted (N,N-dimethylamino)propyl-thiazolidinones and substituted (N,N-dimethylamino)propyl-thiazinone and the lactam carbonyl oxygen. NMR analysis results, supported by molecular mechanic predictions, were in agreement with ab initio calculations. The observed interaction shorting the nitrogen-nitrogen distance in the H1-histamine antagonist, 2-(4-methylphenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidin-4-one (1) could explain its fitting with the H1-antihistaminic pharmacophoric model and the high antihistaminic activity.
Barone
V
V
Dipartimento di Chimica, Università di Napoli Federico II, Napoli, Italy.
Bolognese
A
A
Correale
G
G
Diurno
M V
MV
Gomez-Monterrey
I
I
Mazzoni
O
O
D000478:Alkylation; D003198:Computer Simulation; D006634:Histamine H1 Antagonists / Q000737:chemistry; D006860:Hydrogen Bonding; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D011522:Protons; D013816:Thermodynamics; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry*
D006634:Histamine H1 Antagonists; D007769:Lactams; D011522:Protons; D013844:Thiazoles; D009584:Nitrogen; D010100:Oxygen