Abstract:
:Quantitative structure-activity relationship studies have been performed on two types of sulfonamides with hypoglycemic activity. In the case of the 2-benzenesulfonamidopyrimidines, substituted in the 5 position of the pyrimidine ring a correlation between hydrophobic forces, expressed as Rm values, and the binding to serum albumin as well as to the heights of the equipotent dose has been found. In the series of 2-benzenesulfonamidopyrimidines additionally substituted in the 4 position of the benzene ring, however, a correlation between electronic parameters, expressed as the chemical shift of the anilide NH-(type IIA) and benzylamide NH-(type IIb) protons and the biological response was observed. This correlation indicated a charge-controlled second fixation of these molecules to the receptor. This is supported by the observation of stereospecificity of the blood-glucose lowering effect and also by the importance of a constant distance between the nitrogen in the side chain and the nitrogen atom in the sulfonamido group. The correlation between the logarithm of the biological response and the electric effects of the substituents is linear as long as one homologous series is considered. If the anilide and benzylamide derivatives are combined, a linear correlation can only be obtained if a dummy parameter is included which may account for differences in conformation within these two series of compounds.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Seydel JK,Ahrens H,Losert Wdoi
10.1021/jm00237a002keywords:
subject
Has Abstractpub_date
1975-03-01 00:00:00pages
234-40issue
3eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract::Leishmaniasis is an infection provoked by protozoans belonging to the genus Leishmania. Among the many species and subsepecies of such protozoa, Leishmania donovani chagasi causes visceral leishmaniasis. A β-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism, denominated here LdcCA. Ld...
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更新日期:1996-12-06 00:00:00
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journal_title:Journal of medicinal chemistry
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更新日期:2017-05-11 00:00:00
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journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:1983-03-01 00:00:00
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更新日期:1989-05-01 00:00:00
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更新日期:2012-03-08 00:00:00