The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood is needed.

The 'H-NMR spectra of some 1,3-diacetamino-l.3diphenylpropanes and of the dichloro-Pt(II) complexes of the corresponding diamines are compared with their simulated spectra leading to the stereochemical assignments meso / ruc and eryrhrolthreo, respectively.-IR-spectra data of our "diaqua/sulfato complexes" indicate coordinated as well as free (counterionic) sulfate.'H-NMR-und IR-spektroskopische Untersuchungen an 1,3-Diphenylpropan-1,3-diaminen und lhren Pt(I1)-Komplexen: Stereochemische Zuordnung und Bindung der nicht-aminischen Liganden Die 'H-NMR-Spektren einiger 1,3-Diphenylpropan-l,3-diamine und ihrer Dichlor-Pt(l1)-Komplexe wurden mit den berechneten Spektren verglichen und fiihrten so zu den stereochemischen Zuordnungen meso / ruc bzw. erythro/threo.-Die IR-spektroskopischen Daten unserer "diaqua/sulfato Komplexe" weisen auf koordiniertes und freies (gegenionisches) Sulfat in diesen Verbindungen hin.In part 111') of this series we have reported on the syntheses of the title ligands, while part IV2) deals with the preparation of their Pt(1l) complexes with C1', I, SOj2., and water as additional 1igands.-The 'H-NMR spectra of the ligands and their F't complexes have been compiled in the Experimental Parts of these publications, and the ligands were assigned meso / ruc, and eryrhrolthreo, respectively, without giving an explanation for these indications.Here we describe the arguments of these assignments based on 'H-NMR measurements. Because we are dealing with complicated spin systems with various nuclei, the assignment of the protons by conventional methods is difficult in most cases. Therefore, we have simulated the spectra with the help of a Comparex 8/85 computer (system VM/CMS 5.0) using the program LAME (LAOCOON with Magnetic Equivalence). This is a variation of LAOCOON3) modified by Haigh, Swansea College, Knorr, Munchen, and Poppinger and Vollmerhaus-Koschnik, Regensburg (unpublished). LAME considers nuclei of spin 1/2 only and maximally accepts seven groups of magnetically equivalent spins. If one or several of these groups contain more than one spin, there are additional limitations.At first LAME calculares a theoretic spectrum with line frequences and line itensities in a non-iterative run, using a set of estimated chemical shifts and J-values. In most cases this spectrum does not yet fit the observed one. So, in an iterative run the frequence of a line of the experimental spectrum is attributed to the number of each calculated line. This step is decisive for a good result and, therefore, the lines are attributed according to Hoffmunn et u/!). The subsequent calculation is based on the *) Dedicated to Prof. Dr. H. J . Roth, Tiibingen, on the occasion of his 65th birthday.assumption, that the set of parameters is the best one "which make the sum of the squared residuals of the observables (in this case, transition frequencies) a minim~m"~). k: number of observed linesVeXp -fcalc): difference of frequencies between observed and calculated transition LAME then looks for alterations of those parameter...

207 UI-Azlrldine aus Chalkonen und HydroxylaminAus den hochsubstituierten Chalkonen 1 entstehen nicht die nach von Auwers') zu envanenden Dioxime 2 oder Hydroxyamino-oxime 3 unter Verbrauch von zwei Mol Hydroxylamin. Stan dessen wird nur ein Mol Hydroxylamin verbraucht, und es entstehen tram-konfigurierte 2-BenzoylHighly substituted chalcones 1 do not react with two molecules of hydroxylamine affording dioximes 2 or hydroxyamino-oximes 3 as expected according to von Auwers' procedure'): only one molecule of hydroxylmine is consumed leading to trans-configurated 2-benzoyl-3-phenyI-lHaziridines 4.3-phenyl-1H-aziridine 4.Schdnenberger et al.2)3) have reported on cytostatic Pt-complexes of the 1 .2-diamino-l,2-diphenylethane type. Especially meso-1.2-bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine-dicNo(II) (5) is of interest as it shows low affmity to the estrogen receptor when compared with the Ptfree ligand, it has, however, an enhanced endocrinological activity.In our f i t paper in this fiel$) we have touched on the conformational flexibility of Pt-complexes of 1,Zdiamino-ethanes in comparison with that of 1,3-diaminopropane-Pt-complexes, prepared according to von Auwers') by reacting chalcones with two molecules of hydroxylamine followed by reduction (Scheme 2 in lit.4)). Here we describe an anomality of von Auwers' procedure:When 0.1 mol of the chalcones 1 -prepared from 2,6-dichloro-x-methoxybenzaldehydes 6 and 2,6-dichloror-xmethoxyacetophenones 7 (which in turn could not be prepared by Friedel-Crafts acylation but were obtained from 6a, 6b with H3CMgI and subsequent oxidation) -were treated in a slightly modified von Auwers-procedure') as described4) with 0.263 mol H2NOH.HCl in water/KOH (Experim. Part and Lit.4)) we obtained ketones which contain one N-atom only. 'H-NMR spectra revealed that transconfigurated aziridines were formed: according to Brois') 3~HccH in cis-aziridines is always greater than that in transaziridines. For cis-aziridines J-values of 5.0 -8. 5 Hz are reported, whilst trans-isomers show 2.0 -6.3 Hz. These data are corroborated by Weber and Lieperf@. In our cases J

The title diamines were prepared according to von Auwer's/Arakawa's procedures starting from appropriately substituted benzaldehydes and acetophenones via chalcones, addition of two moles of hydroxylamine, reduction, and separation of diastereomers as N,N′‐bisacetamides. ‐ The Pt(II) complexes of the title ligands are described in the following paper.

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