182141-56-6Relevant articles and documents
Design and synthesis of piperidinyl piperidine analogues as potent and selective M2 muscarinic receptor antagonists
Wang, Yuguang,Chackalamannil, Samuel,Hu, Zhiyong,Clader, John W.,Greenlee, William,Billard, William,Binch III, Herbert,Crosby, Gordon,Ruperto, Vilma,Duffy, Ruth A.,McQuade, Robert,Lachowicz, Jean E.
, p. 2247 - 2250 (2000)
Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration. (C) 2000 Elsevier Science Ltd.
Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography
Sander, Kerstin,Galante, Eva,Gendron, Thibault,Yiannaki, Elena,Patel, Niral,Kalber, Tammy L.,Badar, Adam,Robson, Mathew,Johnson, Sean P.,Bauer, Florian,Mairinger, Severin,Stanek, Johann,Wanek, Thomas,Kuntner, Claudia,Kottke, Tim,Weizel, Lilia,Dickens, David,Erlandsson, Kjell,Hutton, Brian F.,Lythgoe, Mark F.,Stark, Holger,Langer, Oliver,Koepp, Matthias,?rstad, Erik
, p. 6058 - 6080 (2015/08/24)
Increased activity of efflux transporters, e.g., P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), at the blood-brain barrier is a pathological hallmark of many neurological diseases, and the resulting multiple drug resistance represents a major clinical challenge. Noninvasive imaging of transporter activity can help to clarify the underlying mechanisms of drug resistance and facilitate diagnosis, patient stratification, and treatment monitoring. We have developed a metabolically activated radiotracer for functional imaging of P-gp/BCRP activity with positron emission tomography (PET). In preclinical studies, the tracer showed excellent initial brain uptake and clean conversion to the desired metabolite, although at a sluggish rate. Blocking with P-gp/BCRP modulators led to increased levels of brain radioactivity; however, dynamic PET did not show differential clearance rates between treatment and control groups. Our results provide proof-of-concept for development of prodrug tracers for imaging of P-gp/BCRP function in vivo but also highlight some challenges associated with this strategy.
Benzylidene ketal derivatives as M2 muscarinic receptor antagonists
Boyle, Craig D,Chackalamannil, Samuel,Chen, Lian-Yong,Dugar, Sundeep,Pushpavanam, Pradeep,Billard, William,Binch III, Herbert,Crosby, Gordon,Cohen-Williams, Mary,Coffin, Vicki L,Duffy, Ruth A,Ruperto, Vilma,Lachowicz, Jean E
, p. 2727 - 2730 (2007/10/03)
Benzylidene ketal derivatives were investigated as selective M2 receptor antagonists for the treatment of Alzheimer's disease. Compound 10 was discovered to have subnanomolar M2 receptor affinity and 100-fold selectivity against other muscarinic receptors. Also, 10 demonstrated in vivo efficacy in rodent models of muscarinic activity and cognition. (C) 2000 Elsevier Science Ltd.
