Chapters authored
New Potential Beta-3 Adrenergic Agonists with Beta- Phenylethylamine Structure, Synthesized for the Treatment of Dyslipidemia and Obesity
Beta-3 adrenergic receptors have important physiological implications, being expressed in many places in the body, including brown adipose tissue. Of the effects studied in preclinical research on lipid metabolism attributable to stimulation of these receptors, we can mention the increased thermogenesis and metabolic rate in the brown adipose tissue, reduction of body weight in obese diabetic rats, lowering of intra-abdominal and subepithelial fat in nonobese and nondiabetic rats, decrease of triglyceride, and increase of HDL cholesterol levels. Carbohydrate metabolism is also changed by beta-3 adrenergic agonists, the most prevalent effects being blood glucose lowering in diabetic rats, increasing insulin secretion of the pancreas, or increasing glucose tolerance. Metabolic effects of 13 newly synthesized compounds of beta-phenylethylamine structure and reference BRL 37344 were investigated in order to identify a potential affinity for beta-3 adrenergic receptors. The antidiabetic and hypolipemiant effects were investigated on a rat model of alloxan-induced diabetes. The results demonstrated that new beta-phenylethylamine derivatives produced marked biological activity over lipid profile. All compounds have markedly decreased the values of total cholesterol, LDL cholesterol, and triglycerides and also have increased the values of antiatherogenic HDL cholesterol. The effects were significantly more intense than the reference substance BRL 37344.
Part of the book: Adiposity
Synthesis and Pharmacological Research Regarding New Compounds with Quinazolin-4-One Structure
The quinazoline scaffold is found in the chemical structure of many marketed drugs used in CNS disorders as antidepressants, anxiolytics, or hypnotics. Also, the carbamate ester derivatives have different certain therapeutic actions, such as hypnotic or parasympathomimetic ones. We have obtained new 4(3H)-quinazolinones by bringing together in the same structure the quinazoline nucleus and carbamate ester group. The compounds named Q1–Q5 were characterized by measuring the melting points, by determining the infrared and NMR spectra, and by elemental analysis. The pharmacological tests evidenced that the compounds have a very low acute toxicity, lethal doses being >2000 mg/kg bw. The compounds had different actions observed in forced swimming test (FST), tail suspension test (TST), or elevated plus maze (EPM), probably influenced by the presence of different radicals on the nucleus. Thus, Q1 with a nitro group in structure manifested the highest antidepressant effect, showing a reduction of immobilization time in FST and TST. On the other hand, Q3 and Q5, with two groups methoxy, respective ethoxy, had a slight anxiolytic effect, highlighted by an increase of the time spent in open arms and a decrease of the time spent in closed arms of EPM.
Part of the book: Quinazolinone and Quinazoline Derivatives