Zwitterionic uracil derivatives as potent GnRH receptor antagonists with improved pharmaceutical properties.
A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition.
Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers.
Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (Ki=0.45 nM).
Reference values for some haematological, haematochemical, and electrophoretic parameters in the Girgentana goat
The purpose of this study was to determine haematolog ical, haematochemical, and electrophoretic reference values for the Girgentana goat in order to form a basis for clinical interpretation. The study included 348 female Girgentana goats aged from 1 to 6 years. The animals were divided into 3 groups: goats aged 1-2 years (group A), goats aged 3-4 years (group B), and goats aged 5-6 years (group C). Blood samples were collected from each animal every morning at the same time (0800) by means of jugular venipuncture, and red blood cell (RBC), white blood cell (WBC), neutrophil (NEU), lymphocyte (LYM), monocyte (MONO), eosinophil (EOS), and basophil (BASO) counts, and haemoglobin (Hb), packed cell volume percent (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and red cell distribution width (RDW) were recorded. Additionally, the concentration of some haematochemical parameters, including alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), γ-glutamine-transferase (γ-GT), creatinine, β-hydroxybutyrate, urea, non- esterified fatty acids (NEFA), potassium, sodium, and chloride, and the electrophoretic profile (albumin, α1-globulins, α2-globulins, β-globulins, γ-globulins, total proteins and albumin:globulins ratio) were determined. Statistical analysis (one-way analysis of variance (ANOVA)), followed by Bonferroni's test, showed that there were significant differences only in RBC, MCV, EOS, ALT, AST, creatinine, γ-GT, sodium, urea, NEFA, γ-globulins, and the albumin:globulins ratio (P < 0.05 was considered statistically significant). The values determined in the present study contribute to the knowledge of the reference ranges for the Girgentana goat and can be used for monitoring health and disease diagnosis.