Obesity, considered as a chronic disease, represents an important risk factor of cardiovascular, dermatological, gastrointestinal, diabetic, osteoarticular diseases and some cancer types (e.g. colon cancer). There is only a reduced number of drugs available in the pharmaceutical market and furthermore, all of them present significant secondary effects. So, it is mandatory to look for new active compounds in order to avoid or minimize such side effects.
We have developed new alkyl and cycloalkyl compounds disubstituted by pyrazol-3-carboxyamide derivatives that bind, as bivalent ligands, to the cannabinoid receptor type 1 CB1 and are capable of reducing food intake by inhibiting the appetite. The cannabinoid receptor type 1 CB1 takes part in the regulation of the energy consumption. Thus, it represents a commercial validated therapeutic target for the treatment of obesity and appetite control.
The activity of these new compounds has been tested by in vivo assays in Wistar rats showing a substantial decrease in food consumption already at a dose of 0,3mg/kg and in just 30min. after treatment. The effect lasts for at least 4 hours and appears to be dose-dependent.
Innovative Aspects:
Compared with previous drugs that bind to the cannabinoid receptor type 1 CB1, this new family of bivalent pyrazole derivatives constitutes a promising alternative to the known products for the modulation of food intake, in particular for induction of satiety, reduction in body mass gain and regulation of fat metabolism.
These compounds were tested in vivo and showed a significant and sustained effect for 4 hours at different doses including a dose of 0.3 mg/kg, which is commonly used for commercial drugs.
The satiating effect is dose-dependent.
