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 .     

A profit-maximizing supply chain network design model with demand choice flexibility

We present a profit-maximizing supply chain design model in which a company has flexibility in determining which customers to serve. The company may lose a customer to competition if the price it charges is too high. We show the problem formulation and solution algorithm, and discuss computational results.     

Uniform bounds under increment conditions

We apply a majorizing measure theorem of Talagrand to obtain uniform bounds for sums of random variables satisfying increment conditions of the type considered in Gál-Koksma Theorems. We give some applications.

     

Pion correlations and resonance effects in \bar{p}p annihilation to 4\pi^0 at rest

We study correlations in the exclusive reaction at rest with complete reconstruction of the kinematics for each event. The inclusive distribution is fairly flat at small invariant mass of the pion pair while a small enhancement in the double differential distribution is observed for small invariant masses of both pion pairs. Dynamical models with resonances in the final state are shown to be consistent with the data while the stochastic HBT mechanism is not supported by the present findings. Received: 26 February 2002 / Revised version: 22 July 2002 / Published online: 30 August 2002     

Zur quantitativen Eiweissbestimmung im Harn

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Zur Sch?nbein'sehen Reaction auf Blaus?ure

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