Ahmed Mamai

Substituted oxygenated heterocycles and thio-analogues : Synthesis and biological evaluation as melatonin ligands

A new series of substituted oxygenated heterocycles and thio-analogues were synthesized and evaluated as melatonin receptor ligands. The replacement of the indolic moiety of melatonin by heterocyclic skeleton such as 1,4-benzodioxin, 2,3-dihydro-1,4-benzodioxin, chroman, 2,3-dihydro-1,4-benzoxathiin, thiochroman, carrying the amidic chain on the aromatic ring, leads to compounds showing a weak affinity for melatonin receptors, except for the compounds 1cb and 1hb.

Synthesis and Biological Activity of New Melatonin Receptor Ligands

To discover analogues of melatonin with a longer half-life, novel non-indole analogues of the compound, in which the amide group of the side-chain has been reversed, have been prepared and evaluated in binding assays to determine their activity on melatonin receptors. The two most active compounds were those with the N-methylbutyramide side-chain. Butyramide and pentanoylamide side-chains resulted in similar affinities, irrespective of the skeleton tested whereas a propionamide side-chain led to loss of affinity. The biological actity of the molecules was more influenced by the length of the side-chain than by the nature of the skeleton, which had little effect. The results obtained show the relative importance of the length of the side-chain and of the nature of the skeleton in both the binding to and the activity on the melatonin receptor of the retroamide series.

Heterodiene cycloadditions: Synthesis and oxidation of pyrano[3,2,b]indoles into spiro derivatives

Abstract 1-Acetyl-2-benzylidene-2,3-dihydroindol-3-ones reacted with vinyl ethers and vinyl thioethers to afford substituted pyrano[3,2-b]indoles; these compounds were oxidized, using Jones reagent, to spirolactones or to oxo acetals with m-CPBA in the presence of boron trifluoride.

Substituted 2‐Amidomethyl[1,4]benzodioxins: Synthesis and Binding Affinity for the Melatonin Receptors

A novel series of melatonin analogues based on the benzodioxin nucleus is described. The compounds were prepared in several steps from 2-carbethoxy-1,4-benzodioxin. Some of these derivatives competitively inhibited 2-[125I]-iodomelatonin binding to chicken brain and ovine pars tuberalis membranes, albeit with very reduced affinity compared with melatonin.