Fused pyridine derivativesFused pyridine derivatives R 0450 Dihydroquinolines as Novel n-NOS Inhibitors. -The synthesis of dihydroquinolines like (V) and (X) is carried out by two different routes involving either a conrotatory Nazarov cyclization of a phenyl cycloalkenyl ketone as a key step, cf. (I)→(IIII), or a Suzuki coupling of N-pivaloylanilide-derived boronic acids with triflates (VII). The optimal ring size of the annulated ring is achieved with cyclopentane which can be replaced by a tetrahydrofuran ring at an expense of selectivity versus e-NOS. Reasonable potency and fair selectivity are demonstrated by inhibitors (X), possessing a modified benzene substitution pattern. -(JAROCH*, S.; HOELSCHER, P.; REHWINKEL, H.; SUELZLE, D.; BURTON, G.; HILLMANN, M.; MCDONALD, F. M.; Bioorg. Med.

Fused pyridine derivativesFused pyridine derivatives R 0450 Dihydroquinolines with Amine-Containing Side Chains as Potent n-NOS Inhibitors. -5 Dihydroquinolines with amine-containing side chains, e.g. (XIII), are prepared by similar methods (no yields given) and are shown to be potent neuronal nitric oxide synthase (n-NOS) inhibitors. A marked selectivity versus e-NOS of up to approximately 300-fold is observed, whereas i-NOS is moderately inhibited. (XIIIb) and (XIIIc) are the best derivatives in this series. -(JAROCH*, S.; HOELSCHER, P.; REHWINKEL, H.; SUELZE, D.; BURTON, G.; HILLMANN, M.; MCDONALD, F. M.; Bioorg. Med.

Fused pyridine derivativesFused pyridine derivatives R 0450Fluorinated Dihydroquinolines as Potent n-NOS Inhibitors. -Ongoing research leads to the synthesis of novel n-NOS inhibitors such as (X). It is noteworthy that the side chain at the benzene ring is important for a better selectivity. The fluorine atom reduces the basicity of the amidine function which may be crucial for the passage through the blood brain barrier (no yields given). -(JAROCH*, S.; REHWINKEL, H.; HOELSCHER, P.; SUELZLE, D.; BURTON, G.; HILLMANN, M.; MCDONALD, F. M.; MIKLAUTZ, H.; Bioorg. Med.

An Enantioselective Total Synthesis of (+)-Elenoic Acid and the Non-Natural Enantiomers of Tetrahydroalstonine, Aricine, and Reserpinine. -The methyl ester (VIII) of the title acid is prepared from the previously synthesized lactone (I) via Korte rearrangement and isomerization of its epimer (VII). The latter is used for the preparation of the non-natural enantiomers (X) of the title alkaloids. -(HOELSCHER, P.; KNOELKER, H.-J.; WINTERFELDT, E.; Isr. J. Chem. 31 (1991) 3, 187-194; Inst. Org. Chem., Univ. Hannover, D-30167 Hannover, Germany; EN)

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