title: Synthesis and antihypertensive activity of 5-thio-2-pyridinecarboxylic acid derivatives.
abstract: Synthesis of various substituted 5-thio-2-pyridinecarboxylic acids and their derivatives is described by three methods, i.e., displacement of nitrite from methyl 5-nitro-2-pyridinecarboxylate (10) by a thiol anion, alkylation of methyl 5-thio-2-pyridinecarboxylate derived from reaction of the diazotized methyl-5-amino-2-pyridinecarboxylate (5) with thiocyanate followed by borohydride reduction of the product, and alkylation of 5-thio-2-pyridinecarbonitrile followed by hydrolysis. 5-Thio-2-pyridinecarbonitrile was obtained from butyl 6-methyl-3-pyridyl sulfoxide (2) by nitrosation and dehydration of the oxime. Many of these 5-thio-2-pyridinecarboxylic acid derivatives were orally active antihypertensive agents in the spontaneously hypertensive rat. Optimization of the structural parameters for this activity yiedled 5-[m-trifluorobenzyl) thio]-2-pyridinecarboxylic acid (41) and its sulfoxide, 42. Further biological studies with these compounds are described.
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D000882:Haplorhini; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology; D008297:Male; D010848:Picolinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012453:Saimiri; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D010848:Picolinic Acids