Molecular design based on 3D-pharmacophore. Application to 5-HT4 receptor

A definition of a pharmacophore for the 5-HT4 antagonist was carried out by considering a three-dimensional model which correlates the chemical structures of series of antagonists with their biological affinities. A molecular design is described by analyzing the differences between two 3D serotonin pharmacophores. This successful structural modification demonstrates the efficiency of this approach to design new serotonin ligands.     

Synthesis and combinatorial approach of the reactivity of 6- and 7-arylthieno[3,2-d][1,3]oxazine-2,4-diones

This paper describes a general procedure for the synthesis of new substituted thiaisatoic anhydrides or 6- or 7-aryl-1H-thiéno[3,2-d][1,3]oxazine-2,4-diones 3a-j and 4a-f. They were synthesized in large scale under microwave heating conditions with high yields. The reactivity vs nucleophilic reagents of these compounds was studied and permitted to develop a simple combinatorial procedure to synthesize a library of new thiophene ureidoacids 7a-j and 8a-j.     

Pyrrolothienopyrazines. IV. Synthese de derives de 1′amino-5 pyrrolo[1,2-a]thieno[2,3-e]pyrazine

5-Aminopyrrolo[1,2-a]thieno[2-3-3]pyrazine derivatives were obtained by intramolecular cyclisation of N³(1-pyrrolyl)-2-thienylurea derivaties. Synthesis of these latter compounds was achieved from 2-(1-pyrrolyl)-3-thenoylazide via a curtius rearrangement. The H nmr spectra are discussed.     

Pharmacological studies and synthesis of morpholino alkyl derivatives

Seven morpholin derivatives were synthesized (compounds 1-7) and their behavioural effects were evaluated; the elements considered were locomotor activity, motor coordination, catalepsy, stereotyped behaviour and antinociception. All the compounds, at doses of 10-20-40 mg/kg/i.p., induced a reduction of all behavioural elements without a significant antinociceptive effect. These results indicate that these morpholin derivatives affect the central nervous system.     

Pyrazolo[1,5-d]triazines-1,2,4. I. Dérivés pyrazoliques

Pyrazole hydrazides and hydrazines were synthesized from pyrazole-5-carboxylic acid, 4-bromopyrazole-5-carboxylic acid and pyrazole-5-carboxaldehyde. The 5-pyrazolyloxadiazoles and 5-pyrazolylthiadiazoles were obtained by cyclising the pyrazole hydrazides with phosphorus oxychloride and tetraphosphorus decasulphide. Cyclisations in 1,2-dihydro-1-oxo- (or l-thioxo)pyrazolo[1,5-d]-1,2,4-triazines were eventually observed. The structures were assignated by nmr.