Abstractβ‐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 1and2). 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 acids19and20withIC50values ofca.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 sub