Aminothiazole derivatives

#Neuropeptide Y is a 36 amino acid peptide that is widely distributed in the central and peripheral nervous systems. This peptide mediates a number of physiological effects through its various receptor subtypes. Studies in animals have shown that neuropeptide Y is a powerful stimulus of food intake, and it has been demonstrated that activation of neuropeptide Y Y5 receptors results in hyperphagia and decreased thermogenesis. Therefore compounds that antagonise neuropeptide Y at the Y5 receptor subtype represent an approach to the treatment of eating disorders such as obesity and hyperphagia.

#The current approach is aiming at medical intervention to induce weight loss or prevention of weight gain. This is achieved by interfering with appetite control, which is mediated by the Hypothalamus, an important brain region proven to control food intake. Herein, neuropeptide Y (NPY) has been proven to be one of the strongest central mediators of food intake in several animal species. Increased NPY levels result in profound food intake. Various receptors of neuropeptide Y (NPY) have been described to play a role in appetite control and weight gain. Interference with these receptors is likely to reduce appetite and consequently weight gain. Reduction and long-term maintenance of body weight can also have beneficial consequences on co-associated risk factors such as arthritis, cardiovascular diseases, diabetes and renal failure.

#The present invention provides novel thiazole derivatives useful as neuropeptide Y (NPY) receptor ligands, particularly neuropeptide Y (NPY) antagonists. The invention is concerned especially with compounds of formula

#The present invention provides novel thiazole derivatives useful as neuropeptide Y (NPY) receptor ligands, particularly neuropeptide Y (NPY) antagonists. The invention is concerned especially with compounds of formula

#and pharmaceutically acceptable salts and esters thereof; wherein R1 is aryl or heteroaryl, wherein at least one of the two meta positions of each aryl and heteroaryl group is substituted with R5; R2 is hydrogen, alkyl or cycloalkyl; R3 is cycloalkyl, aryl or heteroaryl, wherein at least one of the two ortho positions of each cycloalkyl, aryl and heteroaryl group is substituted with R6; R4 is hydrogen, alkyl or cycloalkyl; R5 is hydrogen, cyano, trifluoromethyl, alkyl-SO2—, amino-SO2—, halogen, alkoxy, alkylcarbonyl or aminocarbonyl; R6 is hydrogen, halogen, cyano, nitro, trifluoromethyl, alkyl, alkoxy, hydroxy or alkoxycarbonyl; and with the proviso that one of R5 and R6 is not hydrogen.

#The compounds of formula I and their pharmaceutically acceptable salts are neuropeptide ligands, for example neuropeptide receptor antagonists and in particular, they are selective neuropeptides Y Y5 receptor antagonists. The compounds of formula I and their pharmaceutically acceptable salts and esters can be used in the prophylaxis or treatment of arthritis, cardiovascular diseases, diabetes, renal failure and particularly eating disorders and obesity.