Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase

β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5′-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (IC₅₀ = 0.7–12 μM ), most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (IC₅₀ ≥ 100 μM ). The only exceptions were the free acids 19 and 20 with IC₅₀ values of ca. 5 μM . It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.     

Synthesis of Benzazepine Analogues of Noscapine

The synthesis of benzazepine analogues of the opium alkaloid noscapine ( 1 ) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester ( 4 ; readily available from 1 ) in several steps. X-Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo-form and thus has the same configuration as 1 .     

Three New Polyoxygenated Steroids from Two Species of the South China Sea Gorgonian Muricella flexuosa and Menella verrucosa Brundin

Three new polyoxygenated steroids, muricesteroid ( 1 ), and menellsteroids A ( 2 ) and B ( 3 ), were isolated from two species of the South China Sea gorgonian Muricella flexuosa and Menella verrucosa Brundin , respectively. The structures of these new compounds were elucidated on the basis of extensive spectroscopic analysis, chemical methods and comparison with known related compounds.     

Anomale änderungen physikalischer Eigenschaften beim heterogenen Zerfall übersättigter Fe-Ni-Cu-Legierungen

Zusammenfassung Einige charakteristische ?nderungen physikalischer Werkstoffeigenschaften beim heterogenen Zerfall übers?ttigter Mischkristalle werden am Beispiel der fl?chenzentrierten Eisen-Nickel-Kupfer-Legierungen beschrieben. Bei der Behandlung des Einflusses der Ausscheidungsvorg?nge auf die Rekristallisationserscheinungen tritt die Bedeutung des übers?ttigungsgrades der zerfallenden festen L?sung für den Ablauf dieser Zustands?nderungen besonders klar zutage. Kritische Stadien der Ausscheidung und der Koagulation der heterogenen Phasen sind bei diesen Legierungen für die Erzeugung besonders hochwertiger magnetischer Eigenschaften verantwortlich. Der vorliegende Bericht wurde von Herrn Prof., Dr. Wo. Ostwald angeregt. Für das diesem Arbeitsgebiet entgegengebrachte Interesse m?chte ich Herrn Prof. Ostwald meinen besten Dank aussprechen.