Michel Barreau

Design, synthesis and binding affinities of novel non-peptide mimics of somatostatin/sandostatin®

Abstract Based on molecular modelling studies of Sandostatin®, sugar-based derivatives I-VI were prepared as potential non-peptide mimics of somatostatin/Sandostatin®. These compounds displaced 3-[ 125 I]-Tyr 11 -SRIF-14 from the somatostatin receptor on membranes of rat cerebral cortex with IC 50 values between 10 and 15 μM.

SRN1 reactions of a tetrasubstituted-1,4-benzoquinone

Abstract The C-alkylation reaction of 2-chloromethyl-3,5,6-trimethyl-1,4-benzoquinone by 2-nitropropane anion is shown to proceed by the S RN 1 mechanism. This mechanism is confirmed by the inhibitory effects of dioxygen, p-dinitrobenzene, cupric chloride and di-tert-butylnitroxide. The dioxygen-induced formation of nitro and nitrite derivatives is found for the first time.

Studies of the reaction of 1,2-dithiole-3-thiones with nucleophiles

Abstract Substituted 1,2-dithiole-3-thiones react with nucleophiles (alkoxides, thiolates) to give various reaction products depending on the nucleophiles and on the substituents on the 1,2-dithiole-3-thione ring. The mechanistic aspects of these reactions are discussed.

Stereoselective synthesis of racemic α-amino-acid derivatives with a β-lactam skeleton: Application of the Staudinger reaction to chiral imines of methyl glyoxylate

Abstract Selected imines of methyl glyoxylate act as good partners in the Staudinger cycloaddition reaction with a series of substituted ketenes. The cis stereoselectivity is almost complete with electron-donor substituted ketenes, but the asymmetric induction is low when imines derived from chiral 1-aryl-ethylamines are used.

Synthesis, anticonvulsant and neuroprotective activities of RP 66055, a riluzole derivative

Abstract RP 66055, a riluzole derivative, has been characterized as a potent anticonvulsant and in vivo neuroprotective agent.

Synthesis and pharmacological properties of 5H, 10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one, a new competitive AMPA/KA receptor antagonist

The excessive release of glutamate, a potent excitatory neurotransmitter, is thought to play an important role in a variety of acute and chronic neurological disorders. Consequently, excitatory amino acid antagonists may have an important therapeutic potential in the treatment of these diseases. Glutamate interacts with at least three types of receptor: 1) NMDA (N‐methyl‐D‐aspartic acid) receptors; 2) AMPA [2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl)propionic acid]/kainic acid (KA) receptors; and 3) metabotropic receptors. Blockade of ionotropic AMPA/KA receptors has been shown to prevent cerebral ischemia insult in experimental models. This article describes the synthesis, pharmacological activity, and neuroprotective properties of 5H,10H‐imidazo[1,2‐a]indeno[1,2‐e]pyrazine‐4‐one (1), a novel AMPA/KA antagonist which showed micromolar affinity at AMPA/KA receptors and competitively inhibited functional responses mediated by these receptors. In mice, 1 had significant anticonvulsive properties and conferred protection against hypobaric hypoxia and KCN intoxication. In rats and gerbils, 1 possesses significant activity in models of global or focal cerebral ischemia, as well as in a model of neurotrauma. Compound 1 was prepared from 2‐bromo‐indanone using two synthetic pathways in two or three steps with moderate (30%) or good (70%) yields, respectively. Drug Dev. Res. 48:121–129, 1999.

1,1-diphenyl-3-dialkylamino-1-silacyclopentane derivatives: A new class of potent and selective 5-HT2A antagonists

Abstract A new series of 1,1-diphenyl-3-dialkylamino-1-silacyclopentanes was synthesized, and most compounds demonstrated moderate to high affinity for the 5-HT2A receptor. A member of this series, compound 1p displays potent antagonist activity after oral administration against both mescaline and DOI-induced head-twitches in mice and rats, with a long duration of action. The dextrorotatory isomer (+)-1p is highly more potent than the levorotatory isomer (−)-1p in in vitro and in in vivo assays.

Une nouvelle reaction de transposition: acces facile a des thiopyranne thiones a partir de (dimethylamino-2 vinyl)-5 alkylthio-3 dithiole-1,2 yliums

Abstract Reduction by potassium borohydride of 5-(2-dimethylaminovinyl) 3-alkylthio 1,2-dithiole yliums yields, 4-alkylthio 2H-thiopyranne 2-thiones, or 2-alkylthio 4H-thiopyranne 4-thiones (depending on the alkyl group); these react with secondary amines to yield 4-amino 2H-thiopyranne 2-thiones.

Construction of 2,3- and 3,4-Functionalized Silacyclopentanes: Synthesis of 6-Aza-2,2-Diphenyl-2-Silabicyclo[3.1.0]Hexane and 6-Aza-3,3-Diphenyl-3-Silabicyclo[3.1.0]Hexane Derivatives

Abstract The synthesis of five azasilabicyclo[3.1.0]hexanes containing an aziridine function in the α- or the β- position of the silicon atom is described. These bicyclic heterocompounds differ by the various substituents (H, Me, CO2Et, CPh3) on the nitrogen atom.

Versatile Methods for the Synthesis of 2-Amino-6-trifluoromethoxy-(nitro)benzothiazoles

Abstract Convenient and regioselective syntheses of all three isomers of mononitro-6-trifluoromethoxy-benzothiazoles, starting from 2-amino-6-trifluoromethoxy-benzothiazole (riluzole) are described.