نبذة مختصرة : Urotensin II, is a vasoactive peptide found in all studied species. It presents a species-variable N-ending linear part and a constant hexocyclic C-ending part which is responsible for the activity. Among the developed ligands, Palosuran, a selective inhibitor of Urotensin II receptor, is interesting in the treatment of renal disorder in diabetic subjects or in some ischemic diseases. In the first part of this work, a succession of pyrido[2,3-d]pyrimidinic compounds has been developed, like those patended by Takeda and also based on the model of Palosuran. Melatonin is an indolic hormone produced during the night by the pineal gland and presenting many properties, the most important of which is the synchronization of the biological clock with the day and night cycle. Agomelatin, a naphthalenic melatoninergic analogue, developed by Laboratoires Servier for the treatment of depression, is an agonist of the MT1 and MT2 receptors and an antagonist of the 5HT2c receptor. On the basis of this model that pyrido[2,3-d]pyrimidine ligands have been developed by substituting the 2, 4 and 6 positions, either by alkylation or by palladium-assisted cross-coupling reaction. Given lateral-chain ramification of Agomelatin, which gave rise to active compounds, this led to the synthesis of pyrido[2,3-d]pyrimidine and imidazo[1,2-a]pyridine analogues bearing the same lateral chain. ; L'Urotensine II est un peptide vasoactif que l'on retrouve chez toutes les espèces étudiées. Elle présente une partie N-terminale linéaire variable selon l'espèce et une partie C-terminale hexocyclique constante et responsable de l'activité. Parmi les ligands développés, le Palosuran, un inhibiteur sélectif du récepteur de l'Urotensine II, présente un intérêt dans le traitement de l'insuffisance rénale du patient diabétique voire dans certaines pathologies ischémiques. Dans la première partie de ce travail de thèse, une série de composés à noyau pyrido[2,3-d]pyrimidine a été développée, tout d'abord, par analogie aux structures brevetées par Takeda ...
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