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Nitrostyrene Derivatives of Adenosine 5′‐Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase
Author(s) -
Peterli Stefan,
Hubmann Dieter,
Séquin Urs,
Mett Helmut,
Traxler Peter
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770109
Subject(s) - chemistry , adenosine , stereochemistry , epidermal growth factor , tyrosine kinase , inhibitory postsynaptic potential , alkyl , tyrosine , adenosine receptor , receptor , biochemistry , organic chemistry , agonist , neuroscience , biology
Abstract 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 ( IC 50 = 0.7–12 μ M ), most of the modified compounds inhibited the EGF‐R PTK only marginally or were inactive ( IC 50 ≥ 100 μ M ). The only exceptions were the free acids 19 and 20 with IC 50 values of ca. 5 μ M . 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.