| Synthesis and antihypertensive activity of 5-O-substituted derivatives of 5-hydroxypicolinic acid. | |
MedLine Citation:
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PMID: 6674478 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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5-O-Substituted derivatives of 5-hydroxypicolinic acids were synthesized from nojirimycin and studied for their antihypertensive activity in unanesthetized spontaneously hypertensive rats (SHRs) restrained in wire mesh cage and acute toxicity in mice. 5-n-Butoxy-picolinic acid (ND-186) was found to have antihypertensive activity comparable to fusaric acid and lesser acute toxicity. Introduction of halogeno group, in particular trifluoromethyl group to the omega-position of 5-n-butoxy group resulted in the enhancement of antihypertensive activity. The acute toxicity was also lowered 3-5 times compared to that of fusaric acid. Replacement of alkyl group with phenyl group resulted in a slight increment of activity. Some of ester derivatives of ND-186 potentiated the antihypertensive activity and reduced the acute toxicity. There was good correlation between partition coefficient (log P) of ester groups and their antihypertensive activities; compound with higher lipophilicity showed higher antihypertensive activity under the condition of oral administration. However, esterification of other compounds such as 5-halogenoalkoxy- and 5-(substituted) phenoxypicolinic acid was not accompanied with activity increment. Considering from the balance of the antihypertensive activity in SHRs and the acute toxicity in mice, 5-(5',5',5'-trifluoropentoxy)-picolinic acid was selected as a candidate for further evaluation. |
Authors:
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M Hachisu; T Tsuruoka; H Takahashi; H Asaoka; Y Sekizawa; T Koeda; S Inouye |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmacobio-dynamics Volume: 6 ISSN: 0386-846X ISO Abbreviation: J. Pharmacobio-dyn. Publication Date: 1983 Dec |
Date Detail:
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Created Date: 1984-05-29 Completed Date: 1984-05-29 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7901854 Medline TA: J Pharmacobiodyn Country: JAPAN |
Other Details:
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Languages: eng Pagination: 922-31 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / chemical synthesis* Blood Pressure / drug effects Chemical Phenomena Chemistry Heart Rate / drug effects Lethal Dose 50 Male Mice Picolinic Acids / chemical synthesis*, pharmacology, toxicity Rats Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Picolinic Acids |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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