942435-74-7Relevant academic research and scientific papers
Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism
Lange, Jos H. M.,Coolen, Hein K. A. C.,Van Der Neut, Martina A. W.,Borst, Alice J. M.,Stork, Bob,Verveer, Peter C.,Kruse, Chris G.
experimental part, p. 1338 - 1346 (2010/09/18)
Pyrazolines 7-10 were designed as novel CB1 receptor antagonists, which exhibited improved turbidimetric aqueous solubilities. On the basis of their extended CB1 antagonist pharmacophore, hybrid molecules exhibiting cannabinoid CB1 receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting activities were designed. The target compounds 12, 13, 20, and 21 are based on 1 (tacrine) as the AChE inhibitor (AChEI) pharmacophore and two different CB1 antagonistic pharmacophores. The imidazole-based 20 showed high CB1 receptor affinity (48 nM) in combination with high CB1/CB2 receptor subtype selectivity (>20-fold) and elicited equipotent AChE inhibitory activity as 1. Molecular modeling studies revealed the presence of a binding pocket in the AChE enzyme which nicely accommodates the CB1 pharmacophores of the target compounds 12, 13, 20, and 21. 2010 American Chemical Society.
Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists
Kim, Jong Yup,Seo, Hee Jeong,Lee, Sung-Han,Jung, Myung Eun,Ahn, Kwangwoo,Kim, Jeongmin,Lee, Jinhwa
body text, p. 142 - 145 (2009/05/30)
Since the CB1 receptor antagonist SR141716 (rimonabant) was reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target in the treatment of obesity. Several series of derivatives based on diarylimidazolyl oxadiazole an
COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND SEROTONIN REUPTAKE INHIBITION
-
Page/Page column 32, (2008/12/07)
This invention relates to compounds with a combination of cannabinoid-CB1antagonism and serotonin reuptake inhibition to pharmaceutical compositions containing these compounds, to methods for preparing the compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing compositions. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in psychosis, anxiety, depression, attention deficits, cognitive disorders, obesity, drug dependence, Parkinson's disease, Alzheimer's disease, pain disorders, neuropathic pain disorders and sexual disorders. In particular the invention relates to compoundsof the general formula (I): wherein the symbols have the meanings given in the specification.
Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity
Smith, Roger A.,Fathi, Zahra,Achebe, Furahi,Akuche, Christiana,Brown, Su-Ellen,Choi, Soongyu,Fan, Jianmei,Jenkins, Susan,Kluender, Harold C.E.,Konkar, Anish,Lavoie, Rico,Mays, Ronald,Natoli, Jennifer,O'Connor, Stephen J.,Ortiz, Astrid A.,Su, Ning,Taing, Christy,Tomlinson, Susan,Tritto, Theresa,Wang, Gan,Wirtz, Stephan-Nicholas,Wong, Wai,Yang, Xiao-Fan,Ying, Shihong,Zhang, Zhonghua
, p. 2706 - 2711 (2008/12/20)
Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 Ki = 3.7 nM, and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models.
