Gaetano Correale

Synthesis and structure-activity relationships of 2-(substituted phenyl)-3-[3-(N, N-dimethylamino)propyl]-1,3-thiazolidin-4-ones acting as H1-histamine antagonists

2-(Substituted-phenyl)-3-[3-(N,N-dimethylamino)propyl]-1,3-thiazolidi n-4- ones (1-15) showed dependence of the potency of the H1-histamine antagonism on the m- and p-substituents suggesting that the aromatic moiety binds the receptor by a strong pi-interaction. Electron-withdrawing substituents decrease the potency while the electron-donating alkyl substituents, enhancing the aryl HOMO energy, increase the antihistamine activity. The m-substituents with the capability to form hydrogen bonds, seems to share an extra-interaction with hydrogen accepting or donating groups of the histamine receptor and exhibits very high potency.

Thiazolidin-4-one formation. Mechanistic and synthetic aspects of the reaction of imines and mercaptoacetic acid under microwave and conventional heating

Microwave irradiation of a mixture of benzylidene-anilines and mercaptoacetic acid in benzene gives 1,3-thiazolidin-4-ones in very high yield (65-90%), whereas the same reaction performed through using the conventional method, at reflux temperature, requires a much longer time and gives a much lower yield (25-69%). This difference seems to be due to some intermediates and by-products formed during the conventional reaction. On the basis of 1H NMR studies, two different mechanisms, acting in benzene and in DMF, respectively, have been hypothesized for the thiazolidin-4-one system formation.

Observed and calculated 1H- and 13C-NMR chemical shifts of substituted 5H-pyrido[3,2-a]- and 5H-pyrido[2,3-a]phenoxazin-5-ones and of some 3H-phenoxazin-3-one derivativesElectronic supplementary information (ESI) available: 1H and 13C NMR data for compounds 1?17. See http://www.rsc.org/suppdata/ob/b4/b401147c/

Carbon and proton NMR spectra of several substituted 5H-pyrido[3,2-a]-, 5H-pyrido[2,3-a]phenoxazin-5-ones and 3H-phenoxazin-3-one derivatives have been assigned, and the experimental chemical shifts have been compared with the results of density functional calculations employing large basis sets. Solvent effects were explored by means of the polarizable continuum method (PCM), while the (limited) side-chain flexibility of the compounds has been addressed by Boltzmann averaging of the computed spectral parameters over different conformational minima. Overall, the calculated shifts reproduce well the experiment results; thus, the computational procedure represents a feasible and useful complement to multidimensional NMR experiments in the assignment process.

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.