beta-Blockers are widely used in the treatment of cardiovascular disease and act by antagonizing the effects of adrenaline (epinephrine) and noradrenaline (norepinephrine) on beta-adrenergic receptors. All beta-blockers currently used in the treatment of cardiovascular disease contain at least one chiral center and, while most are marketed as racemates, their cardiac antihypertensive activity generally resides in the S-enantiomer. Nebivolol is a third generation beta-blocker that is highly selective for the beta(1)-adrenoceptor. The nebivolol molecule contains four chiral centers and is marketed as a racemate of (+)-nebivolol (SRRR-configuration) and (-)-nebivolol (RSSS-configuration). Nebivolol differs from all other beta-blockers with a hydroxypropanolamine substructure in that its cardiac antihypertensive activity resides in the R-enantiomer at the hydroxy group, whereas all other beta-blockers have antihypertensive activity in the S-enantiomer. Two of the four chiral centers in nebivolol are part of a ring structure and the increased rigidity of this structure may be related to nebivolol's divergence from the standard pharmacophore model of beta-blockers.

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We have synthesized and fully characterized the NK 2 receptor antagonist nepadutant and its by-products using nuclear magnetic resonance (NMR) and restrained molecular dynamics. The agent consists of an active bicyclic hexapeptide combined with a sugar residue. Analysis of the high-performance liquid chromatogram and the mass spectroscopy spectra yields traces of three by-products with the same molecular weight as the main product. The conformation of the molecules in the bicyclic hexapeptide segment, the active region, is well defined, whereas the sugar moiety is disordered. For the peptide region of nepadutant and all of its by-products, the NMR observables can be described by a single backbone conformation, more specifically a L LI, L LII-turn arrangement. The active dipeptide unit Trp^Phe occupies the i+1 and i+2 position of a L LI-turn. The byproduct profile is characterized by different forms of sugars which are caused mainly by isomerization in the process of ring opening. ß

Several 2‐diazo‐1‐oxo‐1,2‐dihydronaphthalene{ (1, 2) have been synthesized by reaction of selected hydroxy compounds and 2‐diazo‐1‐oxo‐1,2‐dihydzonaphthalene‐5‐ and ‐4‐sulfonylchloride, respectively. Photolysis as well as thermolysis of 1 and 2 leads to final products, the nature of which depends on the position of substitution. So, reactions of 5‐substituted derivatives (1) yield the corresponding indene‐3‐carboxylic acids 3 and their esters 5, respectively. In contrast, reactions of 4‐substituted derivatives (2) lead to the formation of the 1‐sulfo‐indene‐3‐carboxylic acid derivatives 4 and 6. Prepared compounds have been characterized by means of mass, ultraviolet, infrared, 1H‐n.m.r. ind 13C‐n.m.r. {pectroscopy.

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