Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase
| Autor: | S. Peterli, Urs Séquin, Peter Traxler, Dieter Hubmann, Helmut Mett |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
chemistry.chemical_classification
biology Stereochemistry Organic Chemistry Nitro compound Biological activity Glutarates Biochemistry Adenosine Catalysis Inorganic Chemistry chemistry Enzyme inhibitor Drug Discovery biology.protein medicine Physical and Theoretical Chemistry Protein kinase A Tyrosine kinase Alkyl medicine.drug |
| Zdroj: | Helvetica Chimica Acta. 77:59-69 |
| ISSN: | 0018-019X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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