Cuong Luu-Duc

Synthèse et propriétés pharmacologiques de quelques thiéno[2,3-d]pyrimidin-4-one 2-thiones

The condensation of substituted 2-amino-3-carbethoxy-thiophenes with methyl, ethyl and phenyl isothiocyanate yields the corresponding thienylthioureas which cyclize in ethanol saturated with dry hydrochloric acid to form 3-substituted thieno [2,3-d]pyrimidin-4-(3H)-one-2-thiones. Thirty-five compounds, 21 thienylthioureas and 14 thienopyrimidin-4-one-2-thiones have been screened for their analgesic and anti-inflammatory activities. The ip administration of these products at a dose of 1000 mg/kg shows that they are not toxic (one excepted). Some compounds show analgesic and anti-inflammatory activities equivalent to those of acetylsalicylic acid.

Novel benzimidazoles as ligands for the strychnine-insensitive N-methyl-D-aspartate-linked glycine receptor

Abstract Two new benzimidazole derivatives were synthesized and evaluated for their ability to inhibit the binding at the strychnine-insensitive N -methyl- d -aspartate(NMDA)-linked glycine receptor. The most potent one, the 4,6-dichlorobenzimidazole-2-carboxylic acid 6 , was found to have submicromolar affinity for this receptor. The result of its functional test suggests that it acts as an antagonist of the NMDA receptor complex. Thus, this class of benzimidazole derivatives seems to constitute a group of potential antagonists for the strychnine-insensitive glycine receptor.

Synthesis of 4-octyl-2H-1,4-benzo-thiazin-3-ones.

Synthesis, physical and analytical properties of 6-alkylacylamino-4-octyl-2H-1,4-benzo-thiazin-3-ones derivatives are described. These new compounds were prepared by acylation and/or alkylation of the amino group under phase transfer catalysis conditions. Acid hydrolysis of the alkylacylamino-2H-1,4-benzo-thiazin-3-ones afforded N-alkylamino-benzothiazin-3-ones. Some of these compounds were evaluated in vitro for possible bacteriostatic activity.

Synthesis and microbiological activity of some 4-butyl-2H-benzo[1,4]thiazin-3-one derivatives

The synthesis and physicochemical properties of 4-butyl-2H-benzo[1,4]thiazin-3-one derivatives are described. These new compounds were synthesised by alkylation in 4-N position and acylation and/or alkylation of 6-NH2 by phase transfer catalysis. Acid hydrolysis of 6-alkylacylamino group yielded 6-alkylamino-4-butyl-2H-benzo[1,4]thiazin-3-ones. The antimicrobial in vitro activity was determined on five compounds.

The intramyocardial fate of [1-14C] palmitate, iodopalmitate and iodophenylpentadecanoate in isolated rat hearts. A contribution to the choice of an iodinated fatty acid as a tracer of myocardial metabolism

Labeled iodinated fatty acids (FAs) have been proposed to explore myocardial metabolism by external detection in man. We have chosen a 16-carbon FA, iodinated in omega position, whereas other authors use an iodophenylated FA. To explore the influence of the presence of an iodine or of an iodophenyl radical on the metabolism of the FA, we have compared, in isolated rat hearts perfused in a recirculating system, the intramyocardial fate of palmitate (PA), iodopalmitate (IPA), and iodophenylpentadecanoate (IPPA), the 3 of them being labeled with C14 in position 1. The addition of the iodine atom brings about a hindrance to the esterification of the FA into triglycerides, but not modification of the myocardial uptake and of the CO2 produced. The addition of the iodophenyl radical impairs both the FA storage and its oxidation, leading to a very high level of free FA. The phospholipid distribution is also modified. Apart from their myocardial use in the isolated rat heart, the 3 FAs were assayed in vitro as a substrate for acylCoA-synthase. As IPA more closely mimics native FA metabolism, it is therefore more suitable than IPPA as a tracer of myocardial metabolism.

Imidazole derivatives of pyrrolidonic and piperidonic acids as potential inhibitors of human placental aromatase in vitro

Inhibitory activities towards human Placental aromatase of novel pyrrolidinone and piperidinone drugs were investigated and compared with those of aminoglutethimide (AG) in vitro. All compounds showing a stronger inhibitory effect than this of AG had the following common structural feature: an imidazole side-chain in C-3 position, with a substituted or non-substituted aromatic ring in the C-2 position and an aliphatic chain (n-butyl or n-octyl) or a phenyl moiety on the nitrogen of the pyrrolidone or piperidone ring. When the C-3 side-chain did not bear any imidazole ring, no activity was observed. Respective Ki values for the competitive inhibition exerted by the more potent inhibitors 10, 11, 13 and 21 with androstenedione as substrate were 19.2, 20.3, 16.8 and 15.4 microM, respectively (Ki AG= 77.0 microM).

Mass Spectrometry of Some Benzylidene Imidazolidinediones and Thiazolidinediones. III- Positive and Negative Electron Impact Mass Spectra of Chlorobenzyl Imidazolidinedione or Thiazolidinedione Compounds

Abstract In the present investigation, a study of the electron-impact mass spectrometry in positive- and negative-ion modes is reported for a series of 3-chlorobenzyl-5-benzylidene-imidazolidine-2,4-dione and -thiazolidine-2,4-dione derivatives previously synthetized.

Mass Spectrometry of Some Benzylidene Imidazolidinediones and Thiazolidinediones. II- chlorobenzyl imidazolidinedione and Fluoro or Chlorobenzyl Thiazolidinedione Compounds

Abstract In the present investigation, a study of the electron impact mass spectrometry data is reported for seven compounds of a series of some 3-(4-chlorobenzyl)-5-benzylidene-imidazolidine-2, 4-diones and 3-(4-fluoro or chlorobenzyl)-5-benzylidene-thiazolidine-2, 4-diones previously synthesized.

Intramyocardial fate of 15-p-iodophenyl-?-methylpentadecanoic acid (IMPPA): Is it a good tracer of fatty acid myocardial uptake?

Iodinated fatty acids (FAs) are now used in Nuclear Medicine to assess, by external detection, myocardial metabolism. Methylated FAs have been proposed as tracers of FA myocardial uptake. IMPPA is a new FA analogue in which a methyl group have been introduced in β position to inhibit β-oxidation and a terminal phenyl group prevents a possible omega oxidation. We have compared the intramyocardial behaviour of this FA with the 15-p-iodophenyl-pentadecanoic acid (IPPA), the straight chain analogue, and with the 15-phenyl-β-methylpentadecanoic acid (MPPA), the 3 of them being labelled with C14 on the carboxyl group, in isolated rat hearts perfused in a recirculating system.

Mass Spectrometry of Some Bromophenacyl Thiothiazolidinones and Thiazolidinediones

Abstract In the present investigation, a study of the electron impact spectrometry is reported for a series of 4-thio-5-arylidene-thiazolidin-2-one, 3-(4-bromophenacyl)-4-thio-5-arylidene-thiazolidin-2-one and 3-(4-bromophenacyl)-5-arylidene-thiazolidine-2,4-dione derivatives previously synthetized.