Jean-Jacques Bosc

Synthesis and antidepressant activity of 5-(1-aryl-4-piperazino)methyl-2-amino-2-oxazolines

Abstract The synthesis of 20 5-(1-aryl-4-piperazino)methyl-2-amino-2-oxazolines is described. Antidepressant activity was observed in mice using classical screening tests. Structure-activity relationships were studied and correlated with the nature of the aromatic substituent. Preliminary lipophilic and electronic properties of one lead compound (COR 3224) have been described.

Synthese organometallique d'α-aminoesters N,N-disubstitues

Abstract Reaction of organozinc compounds with a particular gem-aminoether ester, i.e. methyl-N,N-diethylamino methoxyacetate, leads to α-aminoesters. This method allows the synthesis of compounds having potential biological activity, viz. β-unsaturated α-aminoesters.

Physicochemical and Crystallographic Evidence for Polymorphism of the Racemic Ethyl (2‐Chloromethyl‐2,3‐dihydro‐5H‐oxazolo [3,2‐a]pyrimidin‐5‐one)‐6‐carboxylate

The various crystalline forms of an original bicyclic compound [ethyl (2-chloromethyl-2,3-dihydro-5H-oxazolo[3, 2-a]pyrimidin-5-one)-6-carboxylate); EOC] have been obtained and characterized by powder and single-crystal X-ray diffraction, differential scanning calorimetry (DSC), and infrared (IR) and Raman spectroscopy. At 4 degrees C in methanol, a monoclinic racemate (form II) crystallized from the racemic mixture, whereas at 20 degrees C, an orthorhombic racemate (form I) was isolated in trichloroethylene. By increasing the temperature, a solid-solid transition from the stable form II to the stable form I was observed with a Guinier-Simon camera. A I --> II transformation was observed at ambient temperature by DSC.

Captodative dienes in cycloaddition conditions: synthesis of new bicyclo (3.2.0) hept-3-ene-2-ones

Abstract Aminobicyclo (3.2.0) heptenones and aminonorbornenones were obtained from methylacrylate or acrylonitrile and captodative dienes. They result from respectively (2+2) and (4+2) cycloadditions.

Synthesis and Preliminary Pharmacological Evaluation of New 6-cyano-2,3-dihydro-5H-oxazolo[3,2-a]pyrimidin-5-ones and 2-ethyl(methylenecyanoacetate)-2-iminooxazolidines

One-step ring-annulation of 5-substituted 2-amino-2-oxazolines with diethyl ethoxymethy-lenemalonate yielded 2-substituted 6-carboethoxy-2,3-dihydro-5H-oxazolo[3,2-a]pyrimidin-5-ones. Under the same conditions 2-substituted 6-cyano-2,3-dihydro-5H-oxazolo[3,2-a]-pyrimidin-5-ones and the corresponding 2-ethyl(methylenecyanoacetate)-2-iminooxazo-lidines were obtained from ethyl ethoxymethylenecyanoacetate. Some of these compounds were evaluated in mice for antiparasitic activity.

Synthesis and in vitro cytostatic activity of new β-D-arabino furan[1',2':4,5]oxazolo- and arabino-pyrimidinone derivatives

Abstract A series of nucleoside derivatives was obtained via heteroatom annulation of the amino oxazoline of d-(−)-arabinose. Unequivocal proofs for the stereostructure of some new arabinosyl pyrimidinone derivatives were obtained by X-ray structure analysis. These newly synthesized compounds were then evaluated for their cytostatic activity against murine leukemia (L1210), and human T-lymphocytes (Molt 4/C8 and CEM). Of all the compounds in the series, the protected silylated tricyclic fused pyrimidinone 10 showed the most significant antitumor activity against murine leukemia L1210 (IC50 =6μM), and human T-lymphocytes cells Molt 4/C8 (IC50 =7.9μM) and CEM/0 cell lines (IC50 =7.5μM). None of the compounds exhibited significant antiviral inhibitory activities.

Synthesis, Antitumour and Anti-HIV Screening of Oxazolidines and Oxazolidinones Derivatives

Some N-phenyl(thio)carbamoyl-2-iminooxazolidines and 2-oxazolidinones were synthesized via 2-amino-2-oxazolines and tested as antiviral and antitumour agents. Moderate antitumour activity was found for the 5-(1-phenyl-4-piperazinyl)methyl substituted compounds.

Derivatization of (′)-5-[(2-methylphenoxy)methyl]-2-amino-2-oxazoline, an imidazoline binding sites ligand, with (+)-(R)-α-methylbenzyl isocyanate for drug monitoring purposes

The derivatization of racemic 5-[(2-methylphenoxy)methyl]-2-amino-2-oxazoline, developed as an imidazoline binding sites ligand, with (+)- (R) - α -methylbenzyl isocyanate was performed in chloroform. The reaction led to two pairs of diastereomers, which were separated by RP-HPLC. A kinetic study of the derivatization reaction was achieved in order to establish conditions suitable for experimental drug monitoring.

The Reactivity of Related 6-Amino- and 5,6-Diaminouracils Derived from 2-Amino-5-(phenoxymethyl)-2-oxazoline: Efficient Access to Bicyclic Pyrimidine Derivatives

8-(Dimethylamino)-3-(2-hydroxy-3-phenoxypropyl)--xanthine has been obtained from 6-amino-1-(2-hydroxy-3-phen-oxypropyl)uracil by an azodicarboxylate Michael-type addition involving a reactive diene. 6-Amino-1-(2-hydroxy-3-phenoxy--propyl)uracil was easily prepared from racemic 2-amino-5-(phen-oxymethyl)-2-oxazoline. Moreover, these chemical investigations also led to the identification of a racemic 7-aminooxazolo[5,4- D]pyrimidin-5(6 H)-one, obtained by the condensation reaction of the phosgeniminium chloride, Viehe’s salt, with 5,6-diamino-1-(2-hydroxy-3-phenoxypropyl)uracil.

An Efficient Synthetic Strategy for the Preparation of 2, 3, 6, 7-Tetrahydro-3-phenyl-4H-oxazolo[3, 2-a]-1, 3, 5-triazin-2, 4-diones

An efficient synthesis of 2, 3, 6, 7-tetrahydro-3-phenyl-4H-oxazolo[3, 2-a]-1, 3, 5-triazin-2, 4-diones (4) is described. 2-Amino-2-oxazolines (1) were treated with electrophilic compounds to form, in two steps, 3-carboethoxy-2-phenylcarbamoyl-2-iminooxazolidines (3). These products were cyclized at high temperature in the presence of two equivalents of phenyl isocyanate. The structure of the 2, 3, 6, 7-tetrahydro-3-phenyl-7-methoxymethyl-4H-oxazolo[3, 2-a]-1, 3, 5-triazin-2, 4-dione (4a) was confirmed by X-ray crystallography.