ABSTRACT
3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2, 6-difluorophenol (7) were synthesized in eight and four steps, respectively, starting from 2,6-difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain gamma-aminobutyric acid aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme, indicating that the 2, 6-difluorophenol moiety appears to be able to substitute for a carboxylic acid to increase the lipophilicity of drug candidates.
Subject(s)
Carboxylic Acids/chemistry , Phenols/pharmacology , gamma-Aminobutyric Acid/analogs & derivatives , 4-Aminobutyrate Transaminase/antagonists & inhibitors , Animals , Brain/enzymology , Enzyme Inhibitors/pharmacology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Phenols/chemistry , SwineSubject(s)
Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Fatty Acids, Unsaturated/isolation & purification , Oligosaccharides/isolation & purification , Antifungal Agents/pharmacology , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Fusarium , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Oligosaccharides/chemistry , Oligosaccharides/pharmacologyABSTRACT
Three experiments were conducted using commercially available broiler chicks to study the influence of high levels of pyridoxine on incidence of twisted legs. Chicks were grown in wire floored battery brooders to two weeks of age when they were weighed and visually scored for twisted legs. Supplementation of a diet containing 2.2 mg synthetic vitamin B6/kg with 10 and 20 mg/kg pyridoxine resulted in a significant decrease (P less than or equal to .05) in incidence of twisted legs in Experiment 1. In Experiment 2, supplementation with 30, 60, or 100 mg/kg numerically reduced incidence, but the differences were not statistically significant. Incidence of twisted legs was significantly increased by injecting chicks with .5 ml physiological saline at 1 and 7 days of age in comparison to noninjected controls. Including 10 mg pyridoxine HCl in the saline reduced the incidence but it was still numerically higher than the noninjected controls. Factors other than vitamin B6 nutrition appear to play a more important role in the etiology of twisted legs in broiler chicks.
Subject(s)
Bone Diseases, Developmental/veterinary , Cartilage Diseases/veterinary , Chickens/metabolism , Poultry Diseases/diet therapy , Pyridoxine/therapeutic use , Animals , Bone Diseases, Developmental/diet therapy , Cartilage Diseases/diet therapy , Extremities , MaleABSTRACT
The Oily Bird Syndrome (OBS) was successfully reproduced in broilers under laboratory conditions which included elevated temperatures simulating summer conditions and feeding high energy diets with a relatively wide calorie to protein ratio. No significant difference in incidence of the syndrome was detected in broilers fed a corn-soy diet, or one with 13% animal protein concentrates and 7.5% bakery product, or with a diet containing 10% distillers dried gains with solubles. Substituting animal tallow for poultry oil significantly (P less than .05) increased the incidence of the syndrome. Feeding diets with a more narrow calorie to protein ratio significantly reduced incidence in one experiment, and feeding an unpelleted diet from 3 to 7 weeks of age also significantly reduced the incidence below that of birds fed the same diet in pelleted form. Incidence of OBS was significantly less for birds housed in a separate building with lower temperature conditions than those maintained in a house with a higher environmental temperature. The OBS could best be observed under commercial processing conditions. Results of these experiments show that growing broilers at a high environmental temperature and feeding diets with wide calorie to protein ratios provide conditions conducive to the development of OBS. Further studies will be necessary to determine the specific etiology of the syndrome.
