The synthesis of a series of 2-phenylpyrazolo[4,3-c]quinolin-3-one derivatives and their in vitro biological evaluation as ligands for the benzodiazepine receptor are described. The in vitro activities, as determined by an analysis of GABA shift ratios, and binding affinities of these compounds to BZR are compared in terms of the electronic, lipophilic, and steric effect changes of their substituents.
Stoichiometric Schiff base condensations of sterically bulky primary amines with acenaphthenequinone yield isolable monoimines. In the presence of Fe or other transition metals, the remaining ketone reacts with a second primary amine bearing a pendent donor atom to give asymmetric, tridentate, R-diimine complexes. Upon activation with alumoxanes, these complexes are highly active for the oligomerization of ethylene to linear R-olefins, with turnover numbers (TONs) exceeding 2.5 × 10 6 mol ethylene/mol Fe. Product purities are high, with 1-hexene and 1-octene exceeding 99% purity in most examples.
Stoichiometric Schiff base condensations of sterically bulky primary amines with acenaphthenequinone yield isolable monoimines. In the presence of iron(II) chloride, the remaining ketone reacts with a second primary amine bearing a pendant donor atom to give asymmetric, tridentate, R-diimine complexes that possess remarkable structural variability. A series of NNP and NNS tridentate iron(II) complexes are prepared; these coordination compounds become active catalysts for ethylene oligomerization when activated with methylalumoxanes. X-ray crystallographic studies of the precatalyst complexes confirm that the ligand binds in a tridentate fashion. Correlations between the precatalyst solid-state structures and catalyst activity and R-olefin product distribution are explored.
Structure Activity Relationships of 2-Phenylpyrazolo(4,3-c)quinolin-3-ones and Their N-and O-Methyl Analogues at BenzodiazepineReceptors. -The structure activity relationship of the parent compounds (I), which are high affinity ligands at central benzodiazepine receptors (BZR), cannot be determined unambiguously due to the potential of tautomerism. Thus, methylated derivatives (II) and (III) are synthesized to find out the biologically active tautomers. (IIa) and (IIb) show relatively high affinities for BZR, compared to (IIc) and (III), but less than (I) . The presence of a proton donor in (I) does not appear to substantially contribute to agonist activity of (Ib), but may be essential for the inverse agonist property of (Ia).-(FRYER, R. I.; RIOS, R.; ZHANG, P.; GU, Z.-Q.; WONG, G.; BASILE, A. S.; SKOLNICK, P.; Med. Chem. Res. 3 (1993) 2, 122-130; Dep. Chem., Rutgers, State Univ. N. J., Newark, NJ 07102, USA; EN)
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