title: Novel inhibitors of prolyl 4-hydroxylase. 2. 5-Amide substituted pyridine-2-carboxylic acids.
abstract: A series of 5-[(arylcarbonyl)amino]- and 5-(arylcarbamoyl)pyridine-2-carboxylic acids has been prepared and tested for activity as inhibitors of the enzyme prolyl 4-hydroxylase (EC 1.14.11.2). All the analogues prepared were inhibitors of the enzyme in vitro, the best compounds being equipotent with the known inhibitor pyridine-2,5-dicarboxylic acid (9). Like 9 these amidic analogues were not active in a cultured embryonic chick tendon cell model, considered to be a predictor of in vivo activity. The activity of the amides is not consistent with the model described for the mode of action of 9 with the enzyme and aspects of this are discussed.
authors.affiliation: ICI Pharmaceuticals, Macclesfield, Cheshire, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Tucker
authors.forename: D F
authors.initials: DF
authors.lastname: Thomas
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D010848:Picolinic Acids / Q000737:chemistry* / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D010848:Picolinic Acids; D011725:Pyridines; C043093:2,5-Pyridinedicarboxylic acid; D011393:Procollagen-Proline Dioxygenase; C030614:picolinic acid