357927-31-2Relevant academic research and scientific papers
Discovery of tetrasubstituted imidazolines as potent and selective neuropeptide Y Y5 receptor antagonists: Reduced human ether-a-go-go related gene potassium channel binding affinity and potent antiobesity effect
Sato, Nagaaki,Ando, Makoto,Ishikawa, Shiho,Jitsuoka, Makoto,Nagai, Keita,Takahashi, Hirobumi,Sakuraba, Aya,Tsuge, Hiroyasu,Kitazawa, Hidefumi,Iwaasa, Hisashi,Mashiko, Satoshi,Gomori, Akira,Moriya, Ryuichi,Fujino, Naoko,Ohe, Tomoyuki,Ishihara, Akane,Kanatani, Akio,Fukami, Takehiro
experimental part, p. 3385 - 3396 (2010/03/24)
A series of novel imidazoline derivatives was synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Optimization of previously reported imidazoline leads, 1a and 1b, was attempted by introduction of substituents at the 5-position on the imidazoline ring and modification of the bis(4-fluorphenyl) moiety. A number of potent derivatives without human ether-a-go-go related gene potassium channel (hERG) activity were identified. Selected compounds, including 2a, were shown to have excellent brain and CSF permeability. Compound 2a displayed a suitable pharmacokinetic profile for chronic in vivo studies and potently inhibited D-Trp34NPY-induced acute food intake in rats. Oral administration of 2a resulted in a potent reduction of body weight in a diet-induced obese mouse model.
Novel imidazonline compounds
-
, (2008/06/13)
Compounds represented by the general formula (I): wherein Ar1 and Ar2 are each aryl or heteroaryl; R1 is lower cycloalkyl, —Ar3, or a group of the general formula (a), (b) or (c): and R2 and R3 are each hydrogen, lower cycloalkyl, lower alkenyl, or optionally substituted lower alkyl (with the proviso that when R2 and R3 are simultaneously hydrogen, Ar1, Ar2 and R1 do not simultaneously represent unsubstituted phenyl). The compounds are useful as treating agents for various NPY-related diseases, for example, circulatory diseases including hypertension, kidney diseases, cardiac diseases, vasospasm and arteriosclerosis; central nervous system diseases including hyperphagia, depression, anxiety, convulsion, epilepsy, dementia, pain, alcohol dependence, and withdrawal symptoms due to abstinence from drugs; metabolic diseases including obesity, diabetes, hormonal disorders, hypercholesterolemia, and hyperlipidemia; sexual dysfunction and reproductive function disorders; digestive diseases including enterokinetic disorders; respiratory diseases; inflammation; or glaucoma.
