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 .     

Delta and singular delta locus for one‐dimensional systems of conservation laws

This work gives a condition for existence of singular and delta shock wave solutions to Riemann problem for 2×2 systems of conservation laws. For a fixed left‐hand side value of Riemann data, the condition obtained in the paper describes a set of possible right‐hand side values. The procedure is similar to the standard one of finding the Hugoniot locus. Fluxes of the considered systems are globally Lipschitz with respect to one of the dependent variables. The association in a Colombeau‐type algebra is used as a solution concept. Copyright © 2004 John Wiley &Sons, Ltd.     

A simple stereoselective one-pot synthesis of C-nucleosides by 1,3-dipolar cycloaddition of chiral azomethine imines prepared in situ

The NH,NH-dihydrocycloadduct 1 (6-chloro-9,9-dimethyl-7,8-dihydro-9H-pyrazolo[4,3-d]tetrazolo[1,5-b]-pyridazine) obtained by the cycloaddition of 2-diazopropane to 6-chlorotetrazolo[1,5-b]pyridazine, is transformed with protected or unprotected carbohydrates 2, 5, 7,9, 11, 13 and 15 in the presence of methyl acrylate ( 3 ) into the corresponding C-nucleosides 4,6,8,10,12,14 and 16 . In this one-pot synthesis two new chiral centers are formed stereoselectively, dependent on the chirality at C-atom next to aldehydo group in the carbohydrate.