Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists.

After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia.

The new potential invader Linopherus canariensis (Polychaeta: Amphinomidae) in a Mediterranean coastal lake: colonization dynamics and morphological remarks.

The newly introduced polychaete Linopherus canariensis Langerhans, 1881 was found in the Lake of Faro (NE Sicily), during a study comparing the macrobenthos in artificial modules with a neighboring sandy bottom assemblage. Of a total of 4465 specimens, almost 6% showed morphological variation related to branchial turfs and mean body size. The sandy bottom exhibited an average density of 41.86 ind L⁻¹ and a wet biomass of 30.35 mg L⁻¹, whereas the artificial substratum reached levels of 205.29 ind L⁻¹ and 318.44 mg L⁻¹. The highest estimated immigration rate was 3.7 ind L⁻¹d⁻¹ (5.8 mg L⁻¹ d⁻¹). In the artificial microhabitat, 0.4% of the population showed mid-anterior fragmentation, with anterior- (2%), mid- (< 1%) and posterior- (1%) regenerating lineages, which contributed significantly to the dispersion ability of this species. L. canariensis was a selective micro-deposit feeder, even under conditions of reduced sediments. Linopherus was found to be a new potential invader of stressed environments that is probably tied to the import of oysters.

Unusual synthesis of new glycine antagonists via sequential aldol condensation-lactonization-elimination reaction.

Compounds 2 and 3 were designed in order to probe the North-East region of the strichnine-insensitive glycine binding site of the NMDA receptor. The two products were obtained readily by a tandem aldol condensation-lactonization-elimination step which affords the desired E isomer with complete regioselection.

Substituted indole-2-carboxylates as potent antagonists of the glycine binding site associated with the NMDA receptor.

A novel series of indole-2-carboxylate analogues of GV150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.