Mercaptopyridinecarboxylic Acids, Synthesis and Hypoglycemic Activity

[en] 3-Mercaptopicolinic acid (1), its isomers, analogs, and derivatives were prepared and tested for hypoglycemic activity in 48-hr fasted rats. Several compounds {1, 5-mercaptopicolinic acid (3), 4-methyl-3-mercaptopicolinic acid (11), 3-phenylthiopicolinic acid (17), 3-benzylthiopicolinic acid (18), the S-acetyl (20), and S-benzoyl (21), derivatives of 1, the disulfide of 1 (22), and the methyl ester of 1 (24)} were active with 1 being the most potent. p-Methoxybenzyl mercaptan (MBM) was used as a novel sulfurating agent to introduce sulfur in a protected form and was used to prepare 1, 6-mercaptopicolinic acid (4), 5-mercaptonicotinic acid (7), methyl 6-chloro-3-mercaptopicolinate (15), (3-mercapto-2pyridyl)methanol (25), 3-mercaptopicolinamide (30), 2-acetyl-3-mercaptopyridine (35), 3-acetylthiopyridine (54), and 3-mercaptopyridine N-oxyde (59). The protecting group was usually removed in the final step by mercuric acetate in trifluoroacetic acid. The Newman-Kwart route to thiols was also utilized. The hypoglycemic activity of 1 seems highly specific, with relatively minor chemical changes causing marked changes in the ability of closely related compounds to lower glycemic levels in fasted rats.

Disciplines :

Pharmacy, pharmacology & toxicology
Laboratory medicine & medical technology

Author, co-author :

Blank, Benjamin; Smith Kline & French Laboratories > Division of Research and Development

DiTullio, Nicholas W.; Smith Kline & French Laboratories > Division of Research and Development

Miao, Clara K.; Smith Kline & French Laboratories > Division of Research and Development

Owings, Franklin F.; Smith Kline & French Laboratories > Division of Research and Development

Gleason, John G.; Smith Kline & French Laboratories > Division of Research and Development

Ross, Stephen T.; Smith Kline & French Laboratories > Division of Research and Development

Berkoff, Charles E.; Smith Kline & French Laboratories > Division of Research and Development

Saunders, Harry L.; Smith Kline & French Laboratories > Division of Research and Development

Delarge, Jacques ; ULiège - Université de Liège > Institut de Pharmacie

Lapière, Charles-Léon ; ULiège - Université de Liège > Institut de Pharmacie

Language :

English

Title :

Mercaptopyridinecarboxylic Acids, Synthesis and Hypoglycemic Activity

Publication date :

1974

Journal title :

Journal of Medicinal Chemistry

ISSN :

0022-2623

eISSN :

1520-4804

Publisher :

American Chemical Society (ACS), Washington, United States - District of Columbia

Volume :

Issue :

Pages :

1065-1071

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Received January 14, 1974 and presented in part at the 167th National Meeting of the American Chemical Society, Los Angeles,Calif., April 1, 1974

Available on ORBi :

since 22 May 2025

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