B-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 (ICs0 = 0.7-12 p~) , most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (K5, 2 100 VM). The only exceptions were the free acids 19 and 20 with IC,, values of ca. 5 PM. 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.

Several N-phenylpyrrole carboximides were synthesised using acyl isocyanates as intermediates.

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During the synthesis of a series of carboximides using acyl isocyanates [1], the title compound 3 was synthesised in a model reaction from 3-phenyl-2-propynoyl isocyanate (2) and ethanol. Isocyanate 2 was generated in situ from the corresponding carboxamide (1) with oxalyl chloride [2]. Compound 3 had been reported previously [3], but we give here a more detailed characterization.To 3-phenyl-2-propynamide (1 [3], 492 mg, 3.39 mmol) in dichloromethane (8 ml), oxalyl chloride (407 ml, 4.75 mmol) was added under argon at room temperature. The mixture was heated to reflux for 5 h and then allowed to cool to room temperature. Ethanol (1 ml, 177 mmol) was added and the mixture stirred for 10 min and the solvent removed in vacuo. The residue was chromatographed on SiO 2 (40 g, dichloromethane) to give 645 mg (89%) of 3 as a colorless solid.