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8‐Substituted Xanthines as Phosphodiesterase Inhibitors: Conformation‐Dependent Lipophilicity and Structure‐Activity Relationships
Author(s) -
Walther Bernard,
Carrupt PierreAlain,
El Tayar Nabil,
Testa Bernard
Publication year - 1989
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.19890720314
Subject(s) - lipophilicity , chemistry , substituent , quantitative structure–activity relationship , tautomer , potency , caffeine , stereochemistry , phosphodiesterase , enzyme , organic chemistry , biochemistry , in vitro , medicine , endocrinology
The 8‐substituted xanthines 1 – 21 (including compound S 9795), caffeine ( 22 ), and the three isomeric dimethyl‐xanthines 23 – 25 (see Table 1 ), were examined for their lipophilic behaviour using a reversed‐phase HPLC technique. A number of flexible compounds showed a smaller‐than‐expected lipophilicity which based on conformational and tautomeric calculations were ascribed to the predominance of folded forms. A QSAR analysis of the phosphodiesterase‐inhibitory potency of several compounds showed favourable factors to be a low lipophilicity and the absence of a substituent on the N 7 position.