PMID: 7452695Dec 1, 1980

Synthesis and antihypertensive activity of 5-amino-2-pyridinecarboxylic acid derivatives

Journal of Medicinal Chemistry
N FinchH J Povalski


The synthesis of various substituted 5-amino-2-pyridinecarboxylic acids and their derivatives is described by three general methods: (1) reductive alkylation of methyl 5-amino-2-pyridinecarboxylates (2) and subsequent hydrolysis; (2) alkylation of the urethane (9), followed by hydrolysis; and (3) selective NaBH4 reduction of the appropriate amide of (2), followed by hydrolysis. A more specific process was used for the 5-(phenylamino) compound, i.e., nucleophilic displacement of nitrite from methyl 5-nitro-2-pyridinecarboxylate by sodioformanilide and subsequent hydrolysis. Many of these 2-pyridinecarboxylic acid derivatives were potent antihypertensive agents in the spontaneously hypertensive rat (SHR). Optimization of structural parameters for this activity yielded compounds 54, 55, 34, 65, and 22, which were selected for further study in the renal hypertensive dog (RHD). Based on these studies, one compound, 5-[(4-fluorobenzyl)amino]-2-pyridinecarboxylic acid (65), was selected for preclinical toxicity evaluation. Based on the toxicological findings, it was decided not to pursue compound 65 clinically.


Oct 26, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Savvas N GeorgiadesRamon Vilar

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Antihypertensive Agents
Canis familiaris
Hypertensive Disease
Renal Hypertension
Picolinic Acids

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