La mélatonine est une neurohormone sécrétée en période nocturne dans la glande pinéale. Elle régule les rythmes biologiques et influe sur différents processus physiologiques. Son implication ainsi que celle de la sérotonine, un neurotransmetteur, dans certains troubles de l’humeur font des récepteurs associés à ces deux hormones (MT1, MT2 et 5-HT2C respectivement) des cibles innovantes pour le développement de nouveaux antidépresseurs. Dans le cadre de cette thèse, des ligands mixtes mélatoninergiques et sérotoninergiques en série 7-azaindolique ont été synthétisés et testés biologiquement. L’élaboration de dérivés furo[3,2-b]pyridiniques a permis d’évaluer le potentiel biologique de ce squelette original et de mettre au point une nouvelle méthode de synthèse de ce motif. Ces travaux ont également été l’occasion d’étudier l’influence sur l’affinité et l’activité mélatoninergiques de la présence de différents groupements aryles plus ou moins volumineux en position 2 du noyau. Le dernier objectif a consisté dans le développement d’une voie d’accès à des analogues furopyridiniques tricycliques. Le raisonnement méthodologique poursuivi réside dans la mise en place d’une séquence réactionnelle permettant d’accéder aux structures désirées via une procédure courte et efficace. / Melatonin is a neurohormone secreted in the pineal gland during dark phases. This regulator of the biological clock is thus involved in several physiological process. Melatonin and serotonin, a neurotransmitter, are involved in some mood disorders, leading to consider associated receptors (MT1, MT2 and 5-HT2C respectively) as innovative targets for the development of new antidepressant.During this PhD, some 7-azaindolic ligands with both melatoninergic and serotoninergic activity were synthesized and tested from a biological point of view.Elaboration of furo[3,2-b]pyridinic derivatives allow us to evaluate the biological potential of this scaffold and to develop a new synthetic pathway to this pattern. This work has been the opportunity to study the influence of bulky aryl groups at C2 position over affinity and activity of these molecules towards melatoninergic receptors.The last aim consisted in developing a new methodology to access tricyclic furopyridinic analogues with a short and efficient chemical sequence.

The objective of this thesis is to explore new reactivities and to improve luminescent properties of 7-azaindole-containing metal complexes. Selectivity for the activation of toluene and ethyl benzene has been investigated with two cationic Pt(II)(N,N-L) complexes, where N,N-L = 1,2-bis(1-N-7-azaindolyl)benzene (BAB) or bis(1-N-7-azaindolyl)methane (BAM). A high regioselectivity toward toluene and ethyl benzene benzylic C-H activation and a distinct diastereoselectivity for ethyl benzene benzylic C-H activation are demonstrated. Detailed mechanistic studies have been performed, leading to the establishment of both the intermediacy of the η3-benzylic Pt(II) complexes in the reactions and the ligand steric impacts as origins for the distinct diastereoselectivity. A PtMe2 complex of 1-N-(pyridin-2-yl)-7-azaindole (NPA) has been synthesized and found to undergo facile transformation at ambient temperature, resulting in the quantitive formation of a neutral Pt4 molecular square. The mechanism of the transformation process has been examined, establishing a distinct intramolecular C-H driven self-assembly process. The geometrical impacts of the BAB and BAM ligands on the structure and stability of their fac-Pt(IV)Me3 complexes has been investigated. The BAB ligand is more effective than the BAM ligand in stabilizing the five-coordinate Pt(IV)Me3 complexes. With the BAB ligand, a five-coordinate fac-Pt(IV)Me3 complex is obtained; with the BAM ligand, two six-coordinate fac-Pt(IV)Me3 complexes are obtained. In solution, the methyl groups in the BAB complex exchange slowly, but those in the BAM complexes exchange rapidly. Several new 7-azaindolyl derivative ligands via either modifying or altering the BAM and BAB bridging groups have been developed. The syntheses, structures and reactivities of their Pt(II) complexes have been examined, leading to the finding of an unconventional C-Sn oxidative addition reaction. The modification of the NPA ligand via the incorporation of a triarylboron group has been carried out. Several novel Pt(II) and Cu(I) complexes have been synthesized and studied. A Cu(I) complex is found to display exceptionally bright ambient temperature phosphorescence. A series of dinuclear Cu(I) compounds of the 1,2,3,4-tetra(1-N-7-azaindolyl)benzene (TTAB) ligand have been synthesized and examined. The close contacts between the TTAB bridging phenyl ring and the Cu(I) centers are present in the complexes. / Thesis (Ph.D, Chemistry) -- Queen's University, 2008-05-21 18:10:58.628

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