Document Detail

Synthesis and antihypertensive activity of 5-O-substituted derivatives of 5-hydroxypicolinic acid.
MedLine Citation:
PMID:  6674478     Owner:  NLM     Status:  MEDLINE    
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.
M Hachisu; T Tsuruoka; H Takahashi; H Asaoka; Y Sekizawa; T Koeda; S Inouye
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmacobio-dynamics     Volume:  6     ISSN:  0386-846X     ISO Abbreviation:  J. Pharmacobio-dyn.     Publication Date:  1983 Dec 
Date Detail:
Created Date:  1984-05-29     Completed Date:  1984-05-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7901854     Medline TA:  J Pharmacobiodyn     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  922-31     Citation Subset:  IM    
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MeSH Terms
Antihypertensive Agents / chemical synthesis*
Blood Pressure / drug effects
Chemical Phenomena
Heart Rate / drug effects
Lethal Dose 50
Picolinic Acids / chemical synthesis*,  pharmacology,  toxicity
Structure-Activity Relationship
Reg. No./Substance:
0/Antihypertensive Agents; 0/Picolinic Acids

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